Vitamin E deficiency in animals

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. 

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. 

Characteristic lesions of vitamin E deficiency in animals include necrotizing myopathy (inaccurately referred to as nutritional muscular dystrophy), exudative diathesis, nutritional encephalomalacia, irreversible degeneration of testicular tissue, fetal death and resorption, hepatic necrosis, and anemia. Several of these conditions are directly related to peroxidation of unsaturated lipids in the absence of vitamin E, and others can be prevented by synthetic antioxidants or vitamin E. 

It has not been demonstrated that vitamin E is an essential dietary substance for man. None of the pathologic changes of vitamin E deficiency in animals have been shown to have their counterpart in man. 2 Vitamin E has been administered as a therapeutic agent in a number of human diseases but without adequate demonstration of real benefit. 

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). 

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

Much has been said about the positive effects of vitamin E (a-tocopherol) on sexual performance and ability in humans. Unfortunately, there is little scientific rationale to substantiate such claims. The primary reasons for attributing a positive role in sexual performance to vitamin E come from experiments on vitamin E deficiency in laboratory animals. In such experiments the principal manifestation of this deficiency is infertility, although the reasons for this condition differ in males and females. In female rats there is no loss in ability to produce apparently healthy ova, nor is there any defect in the placenta or uterus. However, fetal death occurs shortly after the first week of embryonic life, and fetuses are reabsorbed. This situation can be prevented if vitamin E is administered any time up to day 5 or 6 of embryonic life. In the male rat the earliest observable effect of vitamin E deficiency is immobility of spermatozoa, with subsequent degeneration of the germinal epithelium. Secondary sex organs are not altered and sexual vigor is not diminished, but vigor may decrease if the deficiency continues. 

For a long time, it was considered that, unlike the other vitamins, vitamin E had no specific functions rather it was the major Upid-soluble, radicaltrapping antioxidant in membranes. Many of its functions can be met by synthetic antioxidants however, some of the effects of vitamin E deficiency in experimental animals, including testicular atrophy and necrotizing myopathy, do not respond to synthetic antioxidants. The antioxidant roles of vitamin E and the trace element selenium are closely related and, to a great extent, either can compensate for a deficiency of the other. The sulfur amino acids (methionine and cysteine) also have a vitamin E-sparing effect. 

Vitamin E functions as a lipid antioxidant hoth in vitro and in vivo a numher of synthetic antioxidants will prevent or cure most of the signs of vitamin E deficiency in experimental animals. Polyunsaturated fatty acids undergo oxidative attack by hydroxyl radicals and superoxide to yield alkylperoxyl (alkyl-dioxyl) radicals, whichperpetuate a chain reactionin the lipid-withpotentially disastrous consequences for cells. Similar oxidative radical damage can occur to proteins (especially in a lipid environment) and nucleic acids. 

Vitamin E deficiency in experimental animals was first described by Evans and Bishop in 1922, when it was discovered to be essential for fertility. It was not until 1983 that vitamin E was 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. 

Vitamin E deficiency in experimental animals results in a number of different conditions, with considerable differences between different species in their susceptibility to different signs of deficiency. As shown in Table 4.2, some of the lesions can be prevented or cured by the administration of synthetic antioxidants, and others respond to supplements of selenium. 

Liver XDH activity increases when animals are transferred from a low-protein to a high-protein diet. A two- to five-fold rise in activity of the enzyme was observed after administration of interferon or interferon-inducing agents. Induction of XDH activity has also been reported in vitamin E deficiency in rabbits. The activity of XDH... 

It was found that vitamin E deficiency in the rat resulted in an increase in the incorporation of formate-C into nucleic acids of liver and skeletal muscle (Dinning, 1955). The rats used in these experiments were only mildly deficient in vitamin E, and subsequent experiments were conducted on rabbits in which it is possible to produce severe vitamin E deficiency with relatively short feeding periods. Vitamin E deficiency in the rabbit led to an increased specific activity of nucleic acids in several tissues following formate-C injection (Dinning et al., 1955). Measurements of the specific activity of CO2 expired by these animals indicated that the overall formate pool size was not affected by vitamin E deficiency. The increased specific activity of the tissue nucleic acids then could represent an altered specific activity of the nucleotide precursors or an altered synthetic rate of the tissue nucleic acids. 

The bone marrow nucleic acids from these animals were fractionated into RNA and DNA, and, as may be seen in Table II, vitamin E deficiency in the monkey selectively increased the incorporation of formate into marrow DNA. It is significant in this connection that in the monkey anemia regularly accompanies vitamin E deficiency whereas anemia does not develop in the vitamin E deficient rabbit. 

As was pointed out, an increased specific activity of nucleic acids following injection of formate-C could reflect an increased rate of synthesis of the nucleic acids or an increased specific activity of the precursors. Data on C 02 excretion, following formate-C injections, indicated that the overall formate pool size and specific activity were not influenced by vitamin E deficiency. In an effort to obtain information on the specific activities of the nucleotide precursors, acid-soluble nucleotides were extracted from formate-C Mnjccted animals. It was foimd (Table III) that the acid-soluble nucleotides from the viscera of vitamin E-deficient rabbits previously... 

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. 

An exception is vitamin E, but not for the reasons proposed by W.E. Shute (1972) (43) in his best-seller book. High intake of polyenic acids can cause a vitamin E deficiency in experimental animals and man, mainly if the vitamin E content of food is marginal. 

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). 

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. 

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. 

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