Vitamin E deficiency in humans

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). 

Vitamin E was first described ia 1922 and the name was originally applied to a material found in vegetable oils. This material was found to be essential for fertihty in rats. It was not until the early 1980s that symptoms of vitamin E deficiency in humans were recognized. Early work on the natural distributionj isolation, and identification can be attributed to Evans, Burr, and Emerson (University of California) and MattiU and Olcott (University of Iowa). Subsequendy a group of substances (Fig. 1), which fall into either the family of tocopherols or tocotrienols, were found to act likp vitamin E (1—4). The stmcture of OC-tocopherol was deterniined by degradation studies in 1938 (5). 

The major symptom of vitamin E deficiency in humans is an increase in red blood cell fragility. 

Vitamin E is the most potent fat-soluble antioxidant in human plasma. Although vitamin E was first discovered in 1922, its metabolic function remains an enigma. There are eight different molecular forms with vitamin E antioxidant activity, yet the body preferentially retains a-tocopherol. This preference for a-tocopherol has led the Eood and Nutrition Board in its 2000 Dietary Reference Intakes (DRIs) for vitamin E to recommend that only a-tocopherol, not the other forms, meets human requirements for vitamin E. Moreover, only a-tocopherol is recognized by the hepatic a-tocopherol transfer protein (a-lT P). This protein regulates plasma a-tocopherol concentrations and genetic abnormalities in the protein (or its absence) leads to vitamin E deficiency in humans. 

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. 

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. 

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. 

It is difficult to produce vitamin E deficiency in adult humans. Adult males who were depleted of vitamin E for 6 years showed no symptoms, although serum tocopherol concentrations became very low. However, their erythrocytes lysed more readily than normal when exposed to hydrogen peroxide or other oxidizing agents in vitro. This finding led to the use of low-plasma vitamin E and increased susceptibility of erythrocytes to oxidative hemolysis as criteria for vitamin E deficiency. 

Horwitt [125] has investigated vitamin E requirements in humans by administering a vitamin E-defi-cient diet supplemented with unsaturated fats for the purpose of removing vitamin E. He found that the amount of tocopherol in tissue is inversely related to the amount of unsaturated fat that has been administered. A significant observation was that 30% of the individuals receiving the unsaturated fats also developed duodenal ulcers. Hemorrhagic endarteritis similar to that observed in vitamin E-deficient chicks has been described in a child who, for therapeutic purposes, was fed a diet rich in milk and unsaturated fat, but devoid of 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. 

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. 

Vitamin E deficiency is seen rarely in humans. However, there may be a risk of vitamin E deficiency in premature infants because the placenta does not transfer a-tocopherol to the fetus in adequate amounts. When it occurs in older children and adults, it is usually a result of lipoprotein deficiencies or a lipid malabsorption syndrome. These include patients with abetalipoproteinemia or homozygous hypobeta-lipoproteinemia, those with cholestatic disease, and patients receiving total parenteral nutrition. There is also an extremely rare disorder in which primary vitamin E deficiency occurs in the absence of lipid malabsorption. This disorder is a rare autosomal recessive neurodegenerative disease caused by mutations in the gene for a-TTP. This disorder is known as ataxia with vitamin E deficiency (AVED). Patients with AVED have extraordinary low plasma vitamin E concentrations (<5pgml ) and have an onset between 4 and 18 years, with progressive development of peripheral neuropathy,... 

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. 

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. 

In terms of human dietary requirements, much of the wheat for breadmaking in the United States is produced in selenium-adequate sections of the country. Bread is generally a good source of dietary selenium, Selenomethionine decomposes lipid peroxides and inhibits in vivo lipid peroxidation in tissues of vitamin-E-deficient chicks. Selenocysdne catalyzes the decomposition of organic hydroperoxides. Selenoproteins show a high degree of inhibition of lipid peroxidation in livers of sheep, chickens, and rats, Thus, some forms of selenium exhibit in vivo antioxidant behavior,... 

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. 

II. Ingold, K. U., Webb, A. C., Witter, D., Burton, G. W., Metcalfe, T. A., and Muller, D. P., Vitamin E remains the major lipid-soluble, chain-breaking antioxidant in human plasma even in individuals suffering severe vitamin E deficiency. Arch. Biochem. Biophys. 259, 224-225... 

Radical scavengers such as a-tocopherols prevent oxidative degradation of HA. In tissue culture systems, the addition of Vitamin E to the medium prevents spontaneous degradation of HA,272 as does superoxide dismutase. In Vitamin-E-deficient animals, there is a decrease in GAGs in tissues, including HA 273 This could be reversed by the addition of Vitamin E to diets,274 suggesting that tocopherol supplements can enhance HA in human skin. 

Vitamin E deficiency results in the development of necrotizing myopathy, sometimes including cardiac muscle. This has been called nutritional muscular dystrophy, an unfortunate term, because deficiency of the vitamin is not a factor in the etiology of human muscular dystrophies, and supplements of the vitamin have no beneficial effect. The myopathy responds to selenium, but not to synthetic antioxidants. 

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. 

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