Swine: Vitamin C

According to Zintzen (1975) the signs of vitamin C deficiency in swine include weakness, fatigue, dyspnea, bone pain and hemorrhages of the skin, musculature, adipose tissue and certain organs. Schwager and Schulze (1998) suggested that ascorbic acid is involved in osteoblast formation, matrix mineralization and bone resorption in pigs. In research with a relatively small number of pigs conducted by Grondalen and Hansen (1981), there was a tendency for less severity of lesions in the elbow joint, distal epiphysial ulna plate or medial femur condyle in pigs that received vitamin C supplementation versus control pigs. Ascorbic acid appears to play a prominent role in collagen synthesis related to hydroxylation of proline and lysine intracellularly during the formation of tropocollagen. Therefore, some of the effects of vitamin C deficiency are due to collagen failing to crosslink properly, owing to lack of hydroxyproline and hydroxylysine.

A specific clinical leg-weakness syndrome in growing pigs manifests itself mainly as crooked and (or) deviated forelegs. These signs are indicated by contracted flexor tendons and weak joint ligaments, which become apparent in pigs weighing 30 to 45 kg (66 to 100 lbs) and seem to indicate an impaired development in growing loaded connective tissues (Nielsen and Vinther, 1984). Vitamin C administered to boars (500 mg per kg; 227 mg per lb) of diet during the growing period from 39 to 105 kg (86 to 230 lbs) body weight resulted in straightness of front legs compared to controls (Cleveland et al., 1987a). However, Strittmatter (1977) and Strittmatter et al. (1978) were unable to detect an influence of high levels of dietary ascorbic acid on growth or the severity and incidence of osteochondrosis in pigs. Recently, additional data by Pointillart et al. (1997) also indicated that high intakes of ascorbic acid have no positive effects on bone metabolism and bone characteristics in pigs. However, in a separate report, Denis et al. (1997) indicated that high levels of vitamin C had deleterious effects on trabecular bone formation in young pigs but did not alter the overall bone mass.

According to Chatterjee (1967), degeneration of the ovaries and testes occurs in guinea pigs on an ascorbic acid-free diet, but the effects are associated with general inanition. There is evidence for reduced testosterone synthesis by Leydig cells of the testes of vitamin C-deficient male guinea pigs. The precise role of ascorbic acid in sex steroid biosynthesis has not been established.

In females, there are considerable demands for collagen synthesis and degradation during pregnancy as uterine growth, placental development and fetal development all depend on rapid increases in connective tissue components, of which ascorbic acid plays a critical role. Brown et al. (1970; 1971) evaluated the influence of the level of energy and ascorbate supplementation on hydroxyproline excretion in swine. Their data suggested that when energy is limited, capacity of swine to synthesize ascorbic acid is limited and supplementary ascorbate might increase polymerization of precursor collagen into stable forms. In a study with pregnant sows, Wegger (1994) reported that maternal ascorbic acid deficiency impairs both mineralization in fetal bone and formation of normal osteoid. Defective collagen synthesis and decreased proteoglycan synthesis were suggested to be involved. Wegger and Palludan (1994) provided a more detailed description of the skeletal abnormalities during fetal development in swine resulting from maternal vitamin C deficiency.

Ascorbic acid is also known to enhance absorption of iron from the intestine (Volker et al., 1984). In hematopoiesis, ascorbic acid facilitates the transfer of iron from transferrin (a plasma protein) to ferritin (an organ protein), which serves in the storage of iron in bone marrow, spleen and liver. Ascorbic acid deficiency disrupts this transport of iron between blood plasma and storage organs. In reproductive tissues of the sow the transfer of iron from uteroferrin to transferrin (Buhi, 1981) is likewise facilitated by ascorbic acid. Gipp et al. (1974) reported dietary ascorbic acid supplementation increased the plasma iron level, the degree of saturation of plasma transferrin and the rate of removal from plasma and uptake by red blood cells of iron-59. These authors suggested that ascorbic acid may help overcome iron deficiency induced by high dietary copper either through interfering with copper absorption or increasing absorption and utilization of iron. Voelker and Carlton (1969) had reported previously that excess dietary ascorbic acid had adverse effects on absorption, transport and excretion of copper in miniature swine. Perks and Miller (1996) added ascorbic acid to iron-fortified cow's milk and were unable to detect a long-term effect of ascorbic acid on iron absorption when the fortified milk was supplied to piglets.

Uteroferrin is a purple, progesterone-induced glycoprotein secreted by the uterine endometrial epithelium of the sow and mare that transports iron to the developing conceptus (Roberts and Bazer, 1980). Presumably, this is achieved by the ascorbic acid acting as a chelator to transfer iron from uteroferrin to transferrin. Transferrin would then transfer iron to cells of the hematopoietic system of liver, spleen and bone marrow to meet the need for hemoglobin synthesis and erythrocyte development. This process begins around day 14 of pregnancy as blood islets form in the yolk sac endoderm and continues until near the end of pregnancy when the hematopoietic centers reside principally in bone marrow.

Ascorbic acid content of the sow uterus increases during early pregnancy in association with essentially a doubling in uterine length and a significant increase in uterine collagen content (Renegar et al., 1981). The placental membranes and fetuses are also rich in collagen, the synthesis of which is dependent upon vitamin C.

The possible role of ascorbic acid in steroid metabolism within the pregnant uterus is not known. However, decreased cholesterol content of the adrenal gland is characteristic of ascorbic acid-deficient guinea pigs and would reduce substrate availability for synthesis of sex steroids (Chatterjee, 1967). The interconversion of NADPH2 and NADPH can be influenced by the electron transfer from ascorbic acid to dehydroascorbic acid. The production of reducing equivalents (NADPH2) is required for numerous hydroxylation reactions in sex steroid biosynthesis. The establishment and maintenance of pregnancy in all farm animals is dependent upon maintenance of a corpus luteum that produces progesterone and, in some species, estrogen production by the placenta. Since adequate ascorbic acid concentrations in tissue may be essential for normal sex steroid metabolism by ovarian and fetal-placental tissue, vitamin C would appear to be essential to the reproductive process. Petroff et al. (1996) measured the levels of total ascorbate and oxidized ascorbate in ovarian stroma, follicles and corpora lutea throughout the estrus cycle and during pregnancy. They reported that periods of maximal luteal and follicular function are associated with elevated concentrations of total ascorbate within these tissues. In addition, aging of the corpora lutea was associated with a high partitioning of reduced ascorbate. Petroff et al. (1996) demonstrated that prostaglandin (PGF2) depletes the porcine corpus luteum of vitamin C by inducing secretion of the vitamin into the bloodstream. Thus, these findings support the hypothesis that vitamin C depletion contributes to the demise of the porcine corpus luteum.

Ivos et al. (1971) reported an inverse relationship between ambient temperature and conception rate in sows. Additionally, these authors reported that average conception rate in sows increased when boars were supplemented with either 1 or 2 g daily of ascorbic acid compared to controls (Fig. 1). Lin et al. (1985) observed increased sperm concentration per ejaculate in heat-stressed working boars that received 300 mg ascorbic acid per day as compared to unsupplemented boars. Boars that received the supplemental ascorbic acid also had fewer abnormal sperm cells per ejaculate. Using a Danish mutant strain of pigs that is unable to synthesize ascorbic acid—Osteogenic Disorder (OD) pigs—Palludan and Wegger (1988) investigated the influence of ascorbic acid status on boar performance. Boars from the OD line had histologic anomalies in the spermatogenic epithelium.

Dvorak and Podany (1971) indicated that high ascorbic acid content of boar testes is related to the optimum development of the gonad. Healthy, fertile boar testis averaged 0.4 mg ascorbic acid per g, which is greater than the ascorbic acid concentration in liver. Total ascorbic acid content of testis decreases to about 250 mg in adult life (Dvorak and Podany, 1966). Dvorak (1984) reported that the ascorbic acid concentration in boar semen was higher than the concentration found in blood serum; however, the concentration of ascorbic acid is affected by accessory gland secretion. Dvorak (1984) indicated that the high ascorbic acid level of the male gonadal glands is related to reproductive function. This applies also to accessory glands as evidenced by the fact that ascorbic acid concentration of these tissues and their secretions were reduced by half one month after castration (Dvorak and Podany, 1971). The role of ascorbic acid in these processes is likely associated with the production of male reproductive cells. Ascorbic acid's high concentration in semen is a physiological manifestation of sexual activity of the boar and, therefore, a desirable characteristic.

Disease conditions have been found to affect vitamin C metabolism. Vitamin C is able to protect tissues by enhancing humoral and cellular immune responses in disease (Nockels, 1988). With a vitamin C deficiency, impaired chemotaxis in macrophages and depressed T-lymphocyte response have been reported (Beisel, 1982). Mozalene et al. (1991) reported that dietary vitamin C had a normalizing effect in pigs on the pathologic reaction induced by infection with T. suis eggs. Their conclusion was based on ceruloplasmin levels, which are indicative of the degree of inflammatory response and changed immunological reactivity of the host.

Swine nutritionists have generally formulated diets without vitamin C because the young pig can synthesize ascorbic acid within a week of birth as demonstrated by Braude et al. (1950), and both sow colostrum and milk provide a plentiful source of the vitamin to the nursing pig (Wegger and Palludan, 1984). Hidiroglou and Batra (1995) indicated that the ascorbic acid content of colostrum is more than twice that of subsequently produced milk when measured at seven days of age. In addition, the concentration of ascorbic acid in plasma of piglets at birth (13.1 mg per ml) following uptake of colostrum slowly declined during the first 28 days of age to 3.2 mg per ml. Birke et al. (1993) in a study with a very limited number of sows indicated that restriction of milk intake in piglets by allowing only 12 hours of suckling per day did not influence plasma or tissue ascorbic acid content. Swine researchers have indicated that under certain situations pigs may need supplemental vitamin C for maximum weight gain and feed use (Mahan et al., 1966; Yen and Pond, 1981; Mahan and Saif, 1983; Mahan et al., 1994; de Rodas et al., 1998); however, there is nearly an equal number of reports that did not show enhanced performance (Brown et al., 1970; Partridge and Brown, 1971; Leibbrandt, 1977; Yen and Pond, 1983, 1984, 1987; NRC, 1998). Reasons for this inconsistency may be that unpredictable environmental and psychological stresses imposed on swine may increase requirements for ascorbic acid. In explaining the lack of vitamin C effect on weight gain in their study, Yen and Pond (1988) suggested that the weight gain of the control pigs was so high that further improvement by dietary manipulation may have been unachievable. The age of pigs studied can influence the response to vitamin C (Mahan et al., 1994). Likewise, Cromwell et al. (1970) reported no benefit to adding vitamin C in the diets of growing pigs.

The level of available dietary energy is a major factor in determining the amount of ascorbic acid available to the pig (Brown et al., 1970; Brown et al., 1975; Brown, 1984). Serum ascorbic acid concentrations as well as urinary output are directly related to the level of energy in the diet. It was also found that a minor stress such as individual penning will evoke a positive growth response from supplementary ascorbic acid, especially in animals fed a "low-energy" diet. Dietary energy is able to cause a shift in ascorbic acid synthesis because of restrictions on amount of free glucose available for this synthesis. Brown and King (1977) suggested that glucose level may control the production of ascorbic acid. Dvorak (1974) also concluded that glucose concentration is an important and positive factor influencing the amount of endogenous synthesis of ascorbic acid.

If a need for dietary vitamin C exists in swine, the newly weaned pig would seem to be the class of swine most likely to be deficient. Sow's milk contains a high concentration of vitamin C at parturition, but the level drops dramatically with time toward weaning. For the baby pig, the general consensus is that ascorbic acid blood level increases with colostrum intake, drops at weaning, and slowly increases after seven weeks to the mature level (Wegger and Palludan, 1984).

Handling practices at weaning (especially early weaning), which are generally considered to be stressful, including transport and mixing with unfamiliar pigs, have been shown to deplete ascorbate from the body. Warriss (1979) investigated the concentration of ascorbic acid in adrenal glands of pigs subjected to various pre-slaughter treatments. Warriss (1979) concluded that depletion of ascorbic acid from the adrenal glands could be utilized as a measure of the stress experienced by animals during the pre-slaughter period. Warriss (1981) also investigated the effect of body size on ascorbic acid content and weight of adrenal glands. He concluded that in pigs the concentration of ascorbic acid remained fairly constant as body size increased while the relative adrenal gland weight decreased. However, Kornegay et al. (1986) did not find a significant effect of nursery temperature on the response of weanling pigs to supplemental vitamin C. The humoral immune response and corticoid levels were not influenced by supplemental vitamin D. Yet, in view of decreased plasma vitamin C concentration and dramatic changes in nutritional, social and other environmental factors associated with weaning, it was suggested that the beneficial response from supplemental vitamin C with weanling pigs may be related to suppression of postweaning subclinical disease (Yen and Pond, 1981). In a study with growing pigs between the age of four and seven weeks, (Park and Harrison, 1990) reported an improvement in nursing pig performance (6% improvement in daily gain; 5% improvement in gain:feed) resulting from vitamin C supplementation in tap drinking water.

Spontaneous scurvy as a result of a genetic defect was observed in a swine production herd among two- to three-week-old piglets (Jensen et al., 1983; Jensen and Basse, 1984). Closer observation revealed that all pigs were from the same boar. Analysis of their blood and tissues revealed only a very small concentration of vitamin C. The 3:1 ratio between normal and affected pigs was characteristic of simple autosomal recessive inheritance in matings between nonaffected carriers. Liver microsomes were shown to be incapable of synthesizing ascorbic acid in vitro even with L-gulonolactone as substrate (Jensen and Basse, 1984). Schwager and Schulze (1997; 1998) utilized vitamin E-deficient pigs as animal models to investigate the effect of ascorbic acid on lymphocytes and leukocytes. They reported that ascorbic acid selectively influences the proliferation of B lymphocytes and negatively acts on interleukin-2 production by T lymphocytes when a threshold of saturation is exceeded. Furthermore, it appears that ascorbic acid influences leukocyte function as the production of reactive oxygen intermediates by polymorphonuclear leukocytes decreased in pigs supplemented with ascorbic acid. In agreement with other evidence that vitamin C has a stimulatory effect on the immune responsiveness of swine, Kristensen et al. (1986) indicated that vitamin C-deficient pigs' lymphocytes had a reduced response to the mitogens concanavalin A and phytohemagglutinin.

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