Human Vitamin E Deficiency

Deficiency develops in patients with severe fat malabsorption, cystic fibrosis, chronic cholestatic hepatobiliary disease, and in two rare groups of patients with genetic diseases  

Patients who lack the hepatic tocopherol transfer protein (Section 4.2) tmd suffer from what has been called AVED (ataxia with vitamin E deficiency) are unable to export a-tocopherol from the liver in VLDL. 

In premature inftmts, whose reserves of the vitamin Me inadequate, vittunin E deficiency causes a shortened htilf-life of erythrocytes, which can progress to increased intravascultu hemolysis, and hence hemolytic anemia. In infants treated with hyperbtuic oxygen, there is a risk of damage to the retina (retro-lental fibroplasia), tmd vittimin E supplements may be protective, although this is not firmly established (Phelps, 1987). 

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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. 

Farrell PM, Bieri JG, Fratantoni JF, Wood RE, di Sant Agnese PA. The occurrence and effects of human vitamin E deficiency. A study in patients with cystic fibrosis. J Clin Invest 1977 60 233-41. 

In 2000, the Food and Nutrition Board (FNB) [86] defined a-tocopherol as the only form that meets human vitamin E requirements, because only a-tocopherol has been shown to reverse human vitamin E deficiency symptoms. 

The frequency of human vitamin E deficiency is very rare. In individuals at risk, it is clear that vitamin E supplements should be recommended to prevent deficiency symptoms. What about vitamin E supplement use in normal individuals Dietary changes such as decreasing fat intakes, substituting fat-free foods for fat-containing ones, and increased reliance on meals away from the home have resulted in decreased consumption of a-tocopherol-containing foods. Therefore, intakes of the vitamin E RDA of 15 mg a-tocopherol, may be difficult. Special attention to consuming nuts, seeds, and whole grains will improve a-tocopherol intakes alternatively, multivitamin pills can be consumed. 

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 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. 

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,... 

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. 

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 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 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. 

In rats fed a vitamin E-deflcient diet for 12 weeks and then repleted with a diet containing a highly pnrifled anthocyanin-rich extract (1 g/kg diet), a significant improvement in plasma antioxidant capacity and a decrease in the vitamin E deficiency-enhanced hydroperoxides and 8-oxo-deoxyguanosine concentrations in liver were observed. (The anthocyanin extract consisted of a mixtnre of the 3-glucoside forms of delphinidin, cyanidin, petnnidin, peonidin, and malvidin.) Thus, it appears that anthocyanins can be effective in vivo antioxidants when included in the diet at 1 or 2 g/kg diet. These levels in the diet provide 20 to 40 mg per day, which are much higher amounts on a body weight basis than found in the typical diet of humans. 

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