Swine: Vitamin E

Nafstad and Tollersrud (1970) and Nafstad (1973) reviewed some of the experimental work and reports available at that time concerning vitamin E-selenium deficiency. In 1976, MacDonald et al. provided a comprehensive review of various aspects of the etiology, pathogenesis and biochemistry of vitamin E-selenium responsive diseases. Van Vleet and Kennedy (1989) provided a review of selenium-vitamin E deficiency in swine, including its effects on the liver, heart and skeletal muscle, diagnosis and differential diagnosis and control and prophylactic measures. Mortimer (1983) discussed a variety of factors that may contribute to the deficiency.

Numerous authors have studied relationships between levels of alanine aminotransferase and aspartate aminotransferase activities and vitamin E-deficiency. The findings have not been of consistent diagnostic value (Simesen et al., 1979; Tollersrud and Nafstad, 1970). Young et al. (1976) found correlations between percent peroxide hemolysis and vitamin E intake or serum vitamin E. Fontaine and Valli (1977) concluded that red cell lipid peroxide measurement was a reliable test for vitamin E deficiency in swine. Red cell lipid peroxides were found to be increased in vitamin E-deficient pigs but not in selenium-deficient pigs. Thode-Jensen et al. (1979) reported that both glutathione peroxidase activity and resistance against erythrocyte lipid peroxidation (ELP) measurement were valuable methods for assessing vitamin E or selenium status in growing pigs. Simesen et al. (1982) stated that although blood and liver selenium and blood vitamin E were regarded as the best indicators for selenium-vitamin E deficiencies, determination of glutathione peroxidase activity and ELP may be suitable alternatives. Thode-Jensen et al. (1983) determined that ELP was a more sensitive index of vitamin E status than were vitamin E levels in young pigs. Malm et al. (1976b) reported that providing 0.5 ppm of supplemental selenium to diets of sows prevented the serum enzyme changes commonly associated with vitamin E-selenium deficiency.

Rammell et al. (1988) suggested that rather than analyzing for one analyte, monitoring multiple factors such as feed and tissue vitamin E, selenium and PUFAs would provide a more accurate diagnosis. These authors indicated that liver vitamin E concentration of greater than 10 mmol per kg appeared to be adequate, while less than 2.5 mmol per kg could indicate vitamin E deficiency. The selenium and PUFA measurements would help determine deficiencies in the case that vitamin E concentrations fell to intermediate levels. Ewan (1971) reported that calcium levels were increased in livers of pigs fed diets deficient in selenium and vitamin E and that sodium levels were increased in muscle tissue from this same group.

Vitamin E displays the greatest range of deficiency signs of all vitamins. Deficiency signs differ among species and even within the same species. Blaxter (1962) reported that muscular dystrophy seemed to be the one syndrome commonly encountered in vitamin E deficiency in all species. Fundamentally this is Zenker's degeneration of both skeletal and cardiac muscle fibers (Illus. 1). Connective tissue replacement that follows is observed grossly as white striations in the muscle bundles (Smith, 1970).

Occurrence of muscular dystrophy is worldwide, but its incidence or at least diagnosis, particularly in a mild or subclinical form, varies widely in different countries and regions within countries (McDowell et al., 1983). Considerable research has revealed the positive relationship between selenium content in soil and geographical occurrence of vitamin E-selenium responsive muscular dystrophy. Numerous authors have described ultrastructural alterations in the cardiac tissue (Sweeney and Brown, 1972; Van Vleet et al., 1977a, b) and skeletal muscle (Van Vleet et al., 1976) of pigs with selenium-vitamin E deficiency that had been experimentally induced. Ruth and Van Vleet (1974) reported that a selective destruction of type I skeletal muscle fibers and a lack of phosphorylase activity in type II fibers were evident in experimentally induced selenium-vitamin E deficiency in growing swine. Fontaine et al. (1977b) summarized their studies concerning vitamin E-selenium deficiency with regard to hematological and biochemical changes in young pigs. They reported that serum creatine phosphokinase activities were increased in association with vitamin E deficiency and selenium deficiency and that the interaction was also significant. They concluded that these increases reflect the occurrence of subclinical muscular dystrophy and that selenium and vitamin E deficiencies have additive effects in the induction of skeletal muscular dystrophy. Nafstad (1965) and Nafstad and Nafstad (1968) reported that vitamin E-deficient pigs had nuclear abnormalities in erythroid precursors within their bone marrow, inadequate erythroid production, increased destruction of erythroid cells and abnormalities in the formation of myeloid cells. In 1972, Baustad and Nafstad indicated that piglets born of vitamin E-deficient mothers had morphological abnormalities of blood and bone-marrow cells similar to those reported in growing pigs following vitamin E deficiency. The authors suggested that vitamin E might be regarded as a hemopoietic factor in the newborn piglet. However, results by Fontaine et al. (1977b) suggested that vitamin E is not a limiting factor for normal erythropoiesis in young growing pigs.

Most vitamin E deficiency signs for the pig have been associated with selenium deficiency, and scientists usually refer to a vitamin E and (or) selenium deficiency since it is not clear which is involved and generally dietary levels of both must be low to bring about deficiency signs and lesions. Since the early 1950s, reports in the European literature have revealed tissue degeneration signs in swine under field conditions associated with vitamin E deficiency, with the significance of selenium deficiency not realized until 1957. Muscular dystrophy and hepatosis dietetica (toxic liver dystrophy) were particularly widespread in the swine industry in Sweden. Obel (1953) reported that records from the State Veterinary Medical Institute of Stockholm from 1947 to 1952 revealed that of a total of 4,382 pigs autopsied, more than 10% suffered from hepatosis dietetica. The description of and experimental induction of hepatosis dietetica reported by Obel (1953) was confirmed shortly thereafter by Hove and Seibold (1955). Hepatosis dietetica is characterized by extensive necrosis of the liver.

Selenium-vitamin E deficiencies have been readily produced in swine diets through use of both highly unsaturated fats (i.e., cod-liver oil as in Lannek et al., 1961) and rancid fats. However, naturally occurring vitamin E-selenium deficiencies were not reported in the United States until the late 1960s (Michel et al., 1969), and in the 1970s they became widespread. High incidence of vitamin E-selenium deficiencies in swine was believed to be due to a number of factors (Trapp et al., 1970), including (1) swine raised in complete confinement, without access to pasture, (2) low selenium content in midwestern U.S. feeds, (3) solvent-extracted protein supplements low in vitamin E, (4) limited feeding programs for sows, (5) loss of vitamin E and selenium from corn due to oxidation as a result of air and heat drying or storing high-moisture grains and (6) selection for leaner pigs that require more selenium. Evidence also suggests that moldy feed in bulk-holding bins may produce mycotoxins that either inhibit the uptake of vitamin E in the small intestine or affect the antioxidant balance of cells.

An increase in confinement rearing of swine on concrete floors or slats has been accompanied by a decrease in the utilization of pasture and forages. Such crops are not only excellent sources of vitamin E but also provide the more highly available form of the vitamin, alpha- versus gamma-tocopherol.

Vitamin E-selenium deficiency in swine is often associated with sudden death (Rice and Kennedy, 1989). In most cases clinical signs of the condition were not observed prior to death (Michel et al., 1969; Trapp et al., 1970), although occasionally pigs were observed with clinical signs of icterus, difficult locomotion, reluctance to move and weakness. Clinical signs also include peripheral cyanosis (particularly the ears), dyspnea (abdominal respiration) and a weak pulse, all occurring shortly before death. In many cases the faster-growing, more thrifty-appearing pigs died suddenly.

The most common pathologic lesions include massive hepatic necrosis (hepatosis dietetica) (Illus. 2 , Illus. 3 and Illus. 4), degenerative myopathy of cardiac (Illus. 5) and skeletal (Illus. 6) muscles, edema, esophagogastric ulceration, icterus, nephrosis, hemoglobinuria, acute congestion, hemorrhaging in various tissues (Illus. 7) (Ewan et al., 1969; Trapp et al., 1970; Piper et al., 1975) and yellowish discoloration of adipose tissue ("yellow fat"). Many pathological reports of vitamin E-selenium deficiency note that the most striking lesion was liver necrosis (Trapp et al., 1970), but bilateral paleness of skeletal muscle was the gross lesion most commonly found. In some pigs, microscopic lesions in liver were either absent or minimal, whereas changes in skeletal muscles were extensive. In other cases, the reverse was true. Bengtsson et al. (1978a,b) reported a variety of symptoms of vitamin E and seleniumm deficiency including lesions such as hepatosis dietetica, mulberry heart, muscular degeneration and microangiopathy in weaned pigs fed a selenium-deficient diet. Only the highest vitamin E supplementation level utilized in their study could overcome the symptoms. Dietary induction of mulberry heart and hepatosis dietetica has been studied by numerous authors including Sharp et al. (1970, 1972a). Sharp et al. (1972a) reported that dietary selenium (0.5 ppm) and (or) vitamin E (25 IU per kg of diet) prevented skeletal muscular dystrophy and exudative diathesis. Hakkarainen et al. (1978a) investigated whether providing dietary vitamin E and selenium could reverse the vitamin E-selenium deficiency (VESD) once the syndrome had been allowed to develop. By using the same combination (5 mg alpha-tocopherol acetate and 135 mg selenium per kg diet) that was shown previously to prevent the onset of VESD, the therapy was found to result in recovery from VESD syndrome. However, with less supplementation (5 mg alpha-tocopherol acetate and 45 mg selenium per kg diet), the VESD syndrome was not reversed.

Other conditions reported in swine herds with vitamin E-selenium deficiency include MMA syndrome in sows, spraddled rear legs in newborn pigs, gastric ulcers, infertility, susceptibility to swine dysentery and poor skin condition. These conditions were believed initially to be unrelated to pig deaths from a vitamin E-selenium deficiency. However, after supplementation with dietary vitamin E or injections of selenium and vitamin E, a noticeable reduction in these conditions occurred (Trapp et al., 1970). With regard to gastric ulcers associated with vitamin E deficiency, Bebiak (1977) conducted a preliminary investigation of the mechanism by which an absence of vitamin E could indirectly influence ulcerogenesis. They determined that microvascular endothelial peroxidative disruption of vessels perfusing the nonglandular region of the gastric mucosa was the principal mechanism by which vitamin E was involved in the development of gastric ulcers. Dobson (1967) was unable to detect a beneficial effect of selenium and vitamin E on the prevention of gastric ulceration or improvement of growth rate. In their study pigs were given intramuscularly injections of selenium and vitamin E at three days (0.25 mg selenium + 68 IU vitamin E), two weeks (0.20 mg selenium + 13.6 IU vitamin E) and eight weeks (0.75 mg selenium + 51 IU vitamin E). The pigs were slaughtered for evaluation at between 6 and 6.5 months of age. Studies by Teige et al. (1978) have shown that susceptibility to dysentery resulting from exposure to the spirochete Treponema hyodysenteriae was greatly increased by the combined dietary deficiencies of vitamin E and selenium. Teige and Nafstad (1978) reported ultrastructural changes in colonic epithelial cells in vitamin E-selenium deficient pigs and observed changes that would decrease the resistance to spirochetes and other intestinal factors occurring in swine dysentery. Whitehair et al. (1983b; 1984) provided evidence that the MMA syndrome may be ameliorated by supplementation of the gestation-lactation diet with vitamin E and selenium. In one experiment vitamin E was shown to help reduce the incidence of MMA from 50% to 14% (Ullrey, 1969). Occurrence of MMA was reduced from 39% to 24% in two studies involving 191 farrowings (Ullrey et al., 1971).

Maximum incidence of death due to vitamin E-selenium deficiency generally occurs at six to eight weeks of age with the incidence declining up to the sixteenth week of life, however, conceptuses can be adversely affected prior to parturition, resulting in stillborn pigs (Putnam, 1984). Data by Dvorak (1974) confirmed that the postweaning period of low plasma vitamin E levels presents a health hazard to the young piglets if vitamin E supplementation is not provided. Bostedt (1980) reported that vitamin E deficiency can also occur in fattening and reproductive stages of swine production. Clinical conditions characterized by cellular damage most often occur after a period of stress, such as change of feed or housing, transportation or weaning. A Michigan survey diagnosed vitamin E-selenium deficiencies in swine herds with mortality ranging from 3% to 10% (Michel et al., 1969; Trapp et al., 1970). One producer, however, lost approximately 300 of 800 pigs weaned. Cline et al. (1974) evaluated the effect of supplemental vitamin E (0, 44 or 220 IU per kg) for sows during gestation and lactation on the incidence of vitamin E-selenium deficiency syndrome in sows and their progeny. The sows receiving 0, 44 and 220 IU supplemental vitamin E in their diets had progeny deaths of 53%, 33% and 7%, respectively. Thus, vitamin E in sow diets was found to be partly effective in preventing death and other vitamin E-selenium deficiency symptoms in their progeny.

It has been realized for many years that vitamin E-deficient animals are more subject to the effects of "stress" than normal animals. The concept of stress is, in itself, difficult to define, but experience has shown that dietary and environmental abnormalities of various kinds can lead to clinical signs of disease and death in animals deprived of vitamin E. Death is often associated with unaccustomed muscular activity. Incidence of death in baby pigs is greatly increased because of fighting when animals are weaned and mixed with different litters. Castration is an additional stress that has been implicated in early death of selenium- and vitamin E-deficient pigs (Piper et al., 1975).

At an early age, vitamin E-selenium deficiency is characterized by myocardial damage, also known as nutritional microangiopathy or mulberry heart disease (MHD), that may cause substantial losses within a litter. This is the most serious of disorders, since when heart muscle tissue is damaged the result is usually sudden death. There may be hemorrhagic lesions within the heart that give the characteristic "mulberry" appearance of MHD (for a case description, see Tutt and Gale, 1957). Harding (1960) reported on histopathological observations associated with the disease, which included hemorrhage with parenchymal degeneration and mild perivascular mononuclear infiltration. Grant (1961) thoroughly reviewed the morphological and etiological findings associated with mulberry heart during the early 1960s. In 1989, Nielsen et al. suggested that the development of MHD in Denmark may not always be due to deficiencies of selenium or vitamin E, but might be associated with an individual disposition related to rapid growth.

Some researchers have demonstrated a low tolerance of vitamin E- and selenium-deficient baby pigs to intramuscular injections of iron-dextran for prevention of anemia. At two or three days, piglets die from iron shock if given routine treatment with iron, with death resulting from an iron-induced lipid peroxidation in tissues. Pretreatment with vitamin E, selenium or ethoxyquin was protective against toxic effects of injectable iron (Tollerz and Lannek, 1964). Dvorak (1974) reported that injection of iron-dextran complex at four or two days of age did not negatively affect plasma vitamin E levels in suckling piglets.

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