Vitamin E deficiency

In experimental animals, vitamin E deficiency depresses immune system function, with reduced mitogenesis of B emd T lymphocytes, reduced phagocytosis tmd chemotaxis, emd reduced production of antibodies and interleukin-2. This su ests a signaling role in the immune system (Moriguchi and Muraga, 2000). 

VitEimin E deficiency in experimental animals was first described by Evans and Bishop in 1922, when it wtis discovered to be essential for fertility. It was not until 1983 that vitamin E wcis demonstrated to be a dietary essential for human beings, when Muller and coworkers (1983) described the devastating neurological damage from lack of vitamin E in patients with hereditary abe-talipoproteinemia. 

The existence of a hitherto unknown dietary factor essential for reproduction was described by Evans and Bishop in 1922 and in subsequent papers. It was discovered first in the rat, and detailed studies of the effect of the deficiency in this animal were carried out by Mason. Later Goettsch and Pappenheimer described vitamin E deficiency in guinea pigs and rabbits, and in 1931 they attributed crazy chick disease to a deficiency of this vitamin. Anderson et al found that dogs appeared to need vitamin E in their diet. 

Mason also listed the workers who have described changes in the testes of male rats on a vitamin E-deficient diet. He quoted the list of progressive changes in the sperm in this deficiency, first described by Evans and Burr. These are  

Sperm normal in number, morphology, and motility, but fertilizing power lost. 

Sperm fused in groups, invested by Sertoli cell cuffs, and showing abnormal staining reactions. 

Loss of ability of animal to form a copulation plug. 

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Pure selenium deficiency, without concurrent vitamin E deficiency, is not generally seen except in animals on experimental diets (113). In China, selenium deficiency in humans has been associated with Keshan disease, a cardiomyopathy seen in children and in women of child-bearing ages, and Kashin-Beck disease, an endemic osteoarthritis in adolescents (113). 

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 symptoms of vitamin E deficiency in animals are numerous and vary from species to species (13). Although the deficiency of the vitamin can affect different tissue types such as reproductive, gastrointestinal, vascular, neural, hepatic, and optic in a variety of species such as pigs, rats, mice, dogs, cats, chickens, turkeys, monkeys, and sheep, it is generally found that necrotizing myopathy is relatively common to most species. In humans, vitamin E deficiency can result from poor fat absorption in adults and children. Infants, especially those with low birth weights, typically have a vitamin E deficiency which can easily be corrected by supplements. This deficiency can lead to symptoms such as hemolytic anemia, reduction in red blood cell lifetimes, retinopathy, and neuromuscular disorders. 

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). 

In experimental animals, vitamin E deficiency results in resorption of femses and testicular atrophy. Dietary deficiency of vitamin E in humans is unknown, though patients with severe fat malabsorption, cystic fibrosis, and some forms of chronic fiver disease suffer deficiency because they are unable to absorb the vitamin or transport it, exhibiting nerve and muscle membrane damage. Premamre infants are born with inadequate reserves of the vitamin. Their erythrocyte membranes are abnormally fragile as a result of peroxidation, which leads to hemolytic anemia. 

Chen, L. and Thacker, R. (1986). Vitamin C partially reversed some biochemical changes produced by vitamin E deficiency. Biotechnol. Appl. Biochem. 8, 40-45. 

The longitudinal effects of experimental vitamin E deficiency on visual function in the rat have been studied by Goss-Sampson et al. (1992). After 12 months of deficiency, visual function as assessed by electroretinography was absent or grossly abnormal. This was associated with... 

Patients with abetalipoproteinaemia, a rare inborn disorder of lipoprotein metabolism, are totally deficient in vitamin E fiom birth and, if untreated, invariably develop a characteristic pigmentary retinopathy similar to that seen in retinitis pigmentosa and peroxisomal disorders. The same retinopathy has been observed in other patients with severe and chronic vitamin E deficiency. A essive vitamin E replacement therapy in all these patients has been shown either to prevent, to halt the progression of, or in some cases, to improve the characteristic visual abnormalities (Muller and Lloyd, 1982). 

In the bile-duct-ligated rat, hepatic mitochondrial lipid peroxides are increased and correlate with serum levels of alkaline phosphatase, bilirubin and alanine aminotransferase (Sokol et al., 1991). Dietary vitamin E deficiency resulted in relatively higher lipid peroxide and bilirubin... 

Jeffrey, G.P., Muller, D.P.R., Burroughs, A.K., Matthews, S., Kemp, C., Epstein, O., Metcalfe, T.A., Southam, E., Tazir-Melbourcy, M., Thomas, P.K. and McIntyre, N. (1987). Vitamin E deficiency and its clinical significance in adults with primary biliary cirrhosis and other forms of chronic liver disease. J. Hepatol. 4, 307-317. 

Repeated periods of exercise reduce the likelihood of damage to skeletal muscle during subsequent bouts of the same form of exercise and this appears to be associated with an increase in the activity of muscle SOD (Higuchi et al. 1985), a reduced level of lipid peroxidation products during exercise in trained rats (Alessio and Goldfarb, 1988), and a modification of the concentration of antioxidants and activity of antioxidant enzymes in trained humans (Robertson etal., 1991). Packer and colleagues (Quintanilha etui., 1983 Packer, 1984) have also examined the exercise endurance of animals of modified antioxidant capacity and found that vitamin E-deficient rats have a reduced endurance capacity, while Amelink (1990) has reported that vitamin E-deficient rats have an increased amount of injury following treadmill exercise. 

Values are presented as mU/min/mg and mean (SEM) of 4-6 muscles. Muscles were either Incubated without any further treatment, stimulated for 30 min with repetitive tetanii or treated with the calcium ionophore (A23187 - 20 /im) for 30 min. Data presented represent efflux over 90-120 min post-treatment. Animals were fed either a vitamin E-deficient or vitamin E-supplemented diet (Phoenix et al., 1990) for 6 weeks prior to study. Data derived from O Farrell (1994). 

McArdle, A., Edwards, R.H.T. and Jackson, M.J. (1993). Calcium homeostasis during contractile activity of vitamin E deficient skeletal muscle. Proc. Nutr. Soc. 52, 83A. 

Asayama, K., Kooy, N.W. and Burr, I.M. (1986). Effect of vitamin E deficiency and selenium deficiency on insulin reserve and free radical scavenging systems in islets decrease of islet manganosuperoxide dismutase. J. Lab. Clin. Med. 107, 459-463. 

Shvedova, A.A. et al. (2007) Vitamin E deficiency enhances pulmonary inflammatory response and oxidative stress induced by single-walled carbon nanotubes in C57BL/6 mice. Toxicology and Applied Pharmacology, 221 (3), 339-348. 

Suggested Alternatives for Differential Diagnosis Infectious bronchitis, laryngotracheitis, fowl cholera, avian influenza, fowl pox, psittacosis, mycoplasmosis, avian encephalomyelitis, coryza, salmonellosis, Marek s disease and Pacheco s disease in parrots, vitamin E deficiency, and deprivation of water, air, or feed. 

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. 

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. ... 

The presence of dietary carnosine in vitamin E-deficient rats was found to increase mammary tumor latency, while not affecting tumor incidence (Boissoneault et ah, 1998). Another beneficial effect of carnosine in relation to cancer has recently been reported carnosine was shown to inhibit metastasis of hepatocarcinoma SK-Hep-1 cells (Chung and Hu, 2008). Unlike the effects reported above, carnosine did not affect the viability of these cells but instead the dipeptide inhibited cell migration and invasion. The mechanism responsible apparently involves a decrease... 

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. 

Mechanism of Action An antioxidant that prevents oxidation of vitamins A and C, protects fatty acids from aff ack by free radicals, and protects RBCs from hemolysis by oxidizing agents. Therapeutic Effect Prevents and treats vitamin E deficiency. Pharmacokinetics Variably absorbed from the GI tract (requires bile salts, dietary fat, and normal pancreatic function). Primarily concentrated in adipose tissue. Metabolized in the liver. Primarily eliminated by biliary system. 

Axonal degeneration, ophthalmoplegia (however, vitamin E deficiency does not occur clinically). 

Deficiency symptoms In vitamin E deficiency in experimental animals the manifestations are seen in several systems... 

It is indicated in premature infants exposed to high concentration of oxygen, correction of established vitamin E deficiency, in patients at risk of developing vitamin E deficiency, nocturnal muscle cramps, intermittent claudication, fibrocystic breast disease, coronary artery disease and as an antioxidant. 

Substantial evidence indicates that high plasma levels of lipoprotein remnants and LDL are atherogenic, while high levels of HDL are atheroprotective. Therefore, the class of lipoproteins that is increased or decreased will determine the clinical feature of a patient. Besides the influence on atherosclerosis, high levels of chylomicrons lead to acute pancreatitis, while markedly decreased levels of VLDL and LDL lead to retinal and neurologic disease, probably due to vitamin E deficiency. 

Vitamin E deficiency is normally associated with diseases of fat malabsorption and is rare in humans. Deficiency is characterized by erythrocyte haemolysis and prolonged deficiency can cause neuromuscular dysfunction. Hypervitaminosis E is not common, despite an increased intake of vitamin E supplements. Extremely high doses of the vitamin may interfere with the blood clotting process. 

Vitamin E deficiency is almost entirely restricted to premature infants. When observed in adults, it is usually associated with defec tive lipid absorption or transport. The signs of human vitamin E defi ciency include sensitivity of erythrocytes to peroxide, and the appearance of abnormal cellular membranes. 

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. 

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. 

To some extent the vitamin E requirement may be lessened by the presence in the diet of synthetic antioxidants and by selenium. Much evidence supports a relationship between the nutritional need for selenium and that for vitamin E. Lack of either causes muscular dystrophy in many animals as well as severe edema (exudative diathesis) in chicks. Since vitamin E-deficient rats have a low selenide (Se2 ) content, it has been suggested that vitamin E protects reduced selenium from oxidation.) Vitamin C (ascorbic acid), in turn, protects vitamin E. 

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