Experimental Vitamin E Deficiency

animal work will be described only sufficiently to allow the reader to appreciate lietter the discussion of the human studies. When it became apparent in 19.55 that the peroxide hemolysis test was dependent not only on the tocopherol level of the blood but also upon the level of linoleic acid (and other autoxidizable components) in the stroma of the erythrocyte, animal experiments were designed to obtain more exact correlations between tocopherol needs and linoleic acid intake. This relationship between linoleic acid content of the diet and the incidence of chick encephalomalacia (Century and Horwitt, 19.58) was not recorded until later (Century et al., 19.59 Century and Horwitt, 19.59) when observation of cerebellar encephalomalacia in an infant that had been fed a commercial cottonseed oil preparation intravenously came to our attention (Horwitt and Bailey, 1959). In the meantime, there had been a number of reports to certify the relationship between linoleic acid consumption and chick encephalomalacia (Dam et al, 19.58 Machlin and Gordon, 1960). With the advent of better gas chromatographic techniques, it was soon possible to show that the linoleic acid content of the cerebellum was diet dependent (Horwitt et al., 1959 Witting et al., 1961). The marked effects of diet on the fatty acids of the mitochondria of chick brains has also been reported (Horwitt, 1981a). The levels of linoleic acid are much lower in brain tissues than in any tissue analyzed to date and this relatively low linoleic acid level may be considered a characteristic of brain tissue. The significance of this difference is not known. It is of interest to note that the current interpretations of the effect of more unsaturated fats on the production of chick encephalomalacia were anticipated by Dam in 1944. 

Because the lipids of the rat muscle are more easily changed than those in the brain, the general thesis that the need for tocopherol by a specific tissue is related to its content of peroxidizable unsaturated fatty acid is better demonstrated by examining the lipid that accumulates in muscle 

Effect of Dietary Fat on Fatty Acid Composition of Neutral Fat AND Phospholipids of Rat Muscle 

Time in Weeks fob the Appearance of Creatinuria in Rats Fed a 19% Saturated Fat Diet and Four 19% Synthetic Fat Diets of Equal Iodine Value (82) Supplying 60 mmoles of Unsatubation per 100 gm op Diet. 

Dietary Fat Tocopherol Level Mg/kg/week allocated 3 times a week  

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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... 

Southam, E., Thomas, P.K., King, R.H.M., Goss-Sampson, M.A. and Muller, D.P.R. (1991) Experimental vitamin E deficiency in rats, morphological and functional evidence of abnormal axonal transport secondary to free radical damage. Brain 114 915-936. 

The interrelations between vitamin E and selenium in cattle and sheep are undoubtedly as complex as they are in other species. It seems reasonable to state that vitamin E, in combatting the toxicity of unsaturated fat, acts as an antioxidant, for its effect can be duplicated by many other antioxidants and redox dyestuffs. Similarly it is indisputable that selenium is a dietar essential for ruminants and that its absence from their diet results in muscular disease. Both unsaturated fat excess and selenium deficiency must produce primary disturbances in the muscle cells. These disturbances need not be common to both, for muscle reacts similarly to a variety of biochemical insult. In the presence of selenium and the absence of unsaturated fat, vitamin E requirements of ruminants appear to be extremely small. The failure to produce reproductive disorders in ruminants by experimental vitamin E deficiency, and the failure to produce muscular disease on fat-free diets deficient in vitamin E but likely to have been adequate in selenium content is evidence of this contention. How vitamin E acts in preventing muscular disease due to selenium deficiency, however, is not known, and this aspect needs elucidation. 

In contrast to experimental vitamin E deficiency in rodents, in humans the major vitamin E deficiency symptom is a peripheral neuropathy characterized by the degeneration of the large caliber axons in the sensory neurons. 

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. 

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

Because of experimental results such as these, vitamin E has been conjectured to restore potency or to preserve fertility, sexual interest, and endurance in humans. No evidence supports these contentions, but because sexual performance is often influenced by mental attitude, a person who believes vitamin E may improve sexual prowess may actually find improvement. The only established therapeutic use for vitamin E is for the prevention or treatment of vitamin E deficiency, a condition that is rare in humans. 

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. 

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

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. 

Although vitamin E deficiency causes infertility in experimental animals (Section 4.4.1), there is no evidence that deficiency has any similar effects on human fertility. It is a considerable leap of logic from the effects of gross depletion in experimental animals to the popular, and unfounded, claims for vitamin E in enhancing human fertility and virility. 

Selenium is an amphoteric element whose chemistry and biochemistry has mnch in common with snlfur. The essentiality of selenium in experimental animals was demonstrated in 1957. It was necessary that the animals be vitamin E deficient to manifest selenium deficiency. Selenium manifests antioxidant activity by its incorporation into selenocysteine and its subseqnent participation at the... 

The signs of a vitamin E deficiency may be quite different in animals and humans. The signs occurring in experimental animals indude impaired reproduction and muscle weakness (muscular dystrophy). Reproductive defects in female animals involve a failure of the fetus to thrive. In males, the deficiency results in an inhibition of sperm production. One feature common to humans and animals is the formation of lesions (pathological structures) in nerves and muscles. The deficiency can cause the degeneration of nerves and the accumulation of a compound called lipofuscin in various tissues, such as muscle. Lipofuscin has an amorphous structure and is thought to be composed of lipid degradation products and croSS linked proteins. 

R16. Rose, D. P., Strong, R., Adams, P. W., and Harding, P. E., Experimental vitamin Ba deficiency and the effect of oestrogen-containing oral contraceptives on tryptophan metabolism and vitamin Ba requirements. Clin. Sci. 42, 465-477 (1972). 

Many years ago Adamstone (1934, 1936) suggested, after extensive histopathologic study of vitamin E-deficient chickens, that the vitamin must exert some controlling influence over cellular proliferation. Mason (1944) carried this suggestion further and hypothesized that vitamin E might somehow influence the synthesis of nuclear chromatin. After these suggestions, which were made almost 30 years ago, there were no experimental studies of nucleic acid metabolism in vitamin E deficiency until the experiments to be described in this review were undertaken. 

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