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Ascorbic Acid Ascorbic acid was recognized as early as 1734 as the factor in fresh fruit and vegetables that prevents the development of scurvy (Chick, 19531. Despite this early recognition, it was not until 1932 that two different re- search groups isolated and identified this compound from mammalian adrenal glands and citrus fruits (Svir- bely and Szent-Gyorgyi, 1932a,b; Waugh and King, 1932~. Ascorbic acid is a white crystalline compound, classified as a carbohydrate, with a molecular weight of 176 and a melting point of 190 to 192C (Bauernfeind, 1982~. It is readily soluble in water, slightly soluble in alcohol and glycerol, and virtually insoluble in ether and chloroform. Ascorbic acid is relatively stable in air. In aqueous solutions, however, ascorbic acid is attacked by oxygen and other oxidizing agents that convert the re- duced form of the vitamin first to dehydroascorbic acid and then on to further oxidation products in irreversible reactions. NUTRITIONAL ROLE Dietary Requirements of Various Species Ascorbic acid can be synthesized from glucose through the intermediate formation of glucuronic acid and gulonic acid (Burns, 1975~. Ascorbic acid appears to be ubiquitous in all plants (Loewus et al., 1975~. It is synthesized in all animal species studied with the excep- tion of humans, several primates, the Indian fruit bat, the guinea pig, a few birds, fish, and invertebrates (Burns, 1957; Ray Chauduri and Chatterjee, 1969; Chat- terjee et al., 1975~. Therefore, ascorbic acid is not con- sidered to be an essential dietary nutrient for most domestic animals and laboratory animals; however, it is physiologically essential for all of them. Biochemical Functions The basic functional property of ascorbic acid is its redox potential ~ + 0.08 mV) whereby the compound can reduce transition metals, thus allowing the vitamin to participate in a number of metabolically important hy- droxylation reactions. For example, a major function of ascorbic acid is as a cofactor in the biosynthesis of colla- gen. Research has indicated that the function of ascor- bic acid in domestic animals is essentially the same as that in humans or guinea pigs. Furthermore, it would appear that there are certain circumstances or periods during which the biosynthesis of ascorbic acid in domes- tic animals may not be sufficient to meet metabolic de- mands. During such periods, such as those of disease or high environmental temperature, exogenous supplies of ascorbic acid have been shown to be beneficial to the health and survival of these animals (Cole et al., 1944; Rydell, 1948; Scott, 1975; Teare et al., 1979; Vaananen and Wekman, 1979; Bauernfeind, 1982~. FORMS OF THE VITAMIN Vitamin C is available as ascorbic acid, ascorbate-2- sulphate, ascorbyl palmitate, and sodium ascorbate. However, for most animals requiring a dietary source of the vitamin, only ascorbic acid (see Figure 9 for reduced and oxidized forms) has significant antiscorbutic prop- erties. For fish such as the catfish, salmon, and trout, there are reports that ascorbate-2-sulphate and ascorbyl palmitate also have antiscorbutic properties (Halver et al., 1975; Brandt et al., 1985~. ABSORPTION AND METABOLISM The site and mechanism of absorption of ascorbic acid may differ between those animals capable of synthesiz 36

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o l c 1 OH-C 11 OH C 1 H-C- O OH-C- H C H2 OH L,Ascorbic acid 0-~ ~ o=c 1 H-C- O OH- C H C H2 OH L,Dehydroascorbic acid FIGURE 9 The reduced and oxidized forms of ascorbic acid. ing the vitamin and those requiring it as dietary source (Hornig, 1975~. In humans and guinea pigs, maximal absorption occurs in the duodenum (Nicholsen and Chornock, 1942; Hornig et al., 1973) by a Na+- dependent, active, carrier-mediated system (Stevenson and Brush, 1969; Stevenson, 1974~. In contrast, ascor- bic acid absorption in the rat, for which it is not a dietary essential, is a passive process that occurs primarily in the ileum (Hornig et al., 1973~. It is assumed that the absorption mechanism of ascorbic acid in domestic ani- mals is similar to that of the rat (Spencer et al., 1963~; however, there is very little information available on this subject. Research on ruminants (Knight et al., 1941; Cappa, 1958) and horses (Errington et al., 1954; Her- rick,1972; laeschke and Keller, 1982) indicates that the efficiency of ascorbic acid absorption by the oral route is low in these species due to ascorbic acid destruction by microbial action or other unknown factors. The efficiency of enteric absorption of ascorbic acid in domestic animals has not been investigated. However, research on humans indicates that the efficiency of as- corbic acid absorption declines as the dosage levels are increased (Kubler and Gehler, 1970; Kallner et al., 1977; Hornig et al., 1980~. More than 70 percent of intakes less than 1 g are absorbed, while intakes greater than 5 g have less than 20 percent absorption. In addition, recent research also indicates that the efficiency of absorption may decline with age (Davies et al., 1984~. Women with an average age of 82.6 years appeared to have approxi- mately one-tenth the absorptive capacity for ascorbic acid of women with an average age of 21.8 years. Studies on the tissue distribution of ascorbic acid in domestic animals have not been extensive, with the ex- ception of the chicken and the trout. In the trout, radio- autographs of intubated trout indicated a heavy Ascorbic Acid 37 concentration of labeled ascorbic acid in the liver, the anterior kidney (which is also known as the head kidney or adrenal gland), the renal kidney, and, particularly, the skin and scales (Halver et al., 1975~. Hilton et al. (1979) found the concentrations of ascorbic acid to be highest in the brain and gonads. In the chicken, the highest concentration of labeled ascorbic acid was observed in the liver with smaller amounts in the kidney, lung, and spleen (Hornig and Frigg, 19791. White muscle ascorbic acid concentrations were not affected by differences in the dietary level of ascorbic acid (Dorr and Nockels, 19711. The metabolism of ascorbic acid in domestic animals has not been extensively studied. Presently, there is very little information available. The known metabolic fate of ascorbic acid varies with species and depends upon the route of introduction and the quantity taken in by the animal (Tolbert et al., 19751. In all species, initial metabolism involves the reversible conversion of ascor- bic acid to dehydroascorbic acid; species' differences in the metabolism of ascorbic acid would appear to occur after this step. In the guinea pig and the rat, there is enzymatic delactonization of dehydroascorbic acid to diketogulonic acid (Kagawa et al., 1960, 1962), which can then be decarboxylated to form carbon dioxide and a number of other compounds (Hornig, 1975~. Carbon di- oxide exhalation is the major route of elimination of ascorbic acid by the guinea pig and the rat. In contrast, no enzymatic delactonization of dehydroascorbic acid has been found to occur in humans (Baker et al., 1966~. Humans eliminate ascorbic acid and a number of its metabolites primarily by way of the urine (Hornig, 1975~. HYPERVITAMINOSIS Despite the claims that ascorbic acid is nontoxic to humans (Pauling, 1970), a number of toxicity symptoms or signs in humans and a number of laboratory animals have been attributed to intakes of large doses of ascor- bic acid. These include oxaluria (Keith et al., 1974), uricosuria (Stein et al., 1976), hypoglycemia (Lewin, 1974), excessive absorption of iron (Cook and Monsen, 1977), diarrhea, allergic responses, and increased activ- ity of degradative enzymes of ascorbic acid (Schrauzer and Rhead, 1973), destruction of vitamin Bl2 (Herbert and Jacob, 1974), and interference with mixed-function oxidase systems in the liver (Peterson et al., 1982; Sut- ton et al., 1982~. However, some of these abnormalities have been incidental and have been noted in uncon- trolled experiments. There are a number of contradic- tory reports as well. For example, studies indicating the destruction of vitamin B~2 by ascorbic acid (Herbert and

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38 En = .= o ._ o An o VO au ~ . o U' = C'? C) c: 04 o 4= Ct to 4= C: ~ o bC $ Ct ~ a In .~ ~0 ~ O En Z Co ~ ~ Co CO Cal ~ Cut - S ~- ~ ~ - at am U) co us us =5 ~ ,= Y ~ ~ z ~ ~ z Al ~ 0 ~ ~ ~ 4= 4= 4= ~ ~ ~ ~ ~ . 04 04 04 ~ a' ~ O O O O z z z z 00 cn a,' ~_ _ S C }_, ..= ~ ~ U) Z C) ~ =0 Z ~ cr: c~ CS: _ ~ _ ~ ~: Ct oo o oo oo LO ~ t~ ~ `~;, ~ - ~ ~o ~s: - - - ~ ~ ~ ~ ~ ~ :r 4,} CD {~ au ~ a~ ~ ~_, c~ l-. ~ ~ ~ ~ ~ 2 =: ~ P~ o~ s- ~ ~ u' cn o o o :L co Co >` o o ,= ~04 ~, o o o o 4= 4= g = ~ ~ ~ ~ ~ ~ V ~ o ~ ~ ~ ~ ~ ~ ~ := so~ ~ o - ' ~. ~ ~ ~ ~ ~ ~ a' ~ ~ au a' b~o o o ~ o ~ o o o c z ~z ~z zzz ~ 4= 4~ 4J ~ 4= ~ 4= 4= ~ 4= - 4= ~ ~ 4= ~ i~ ~ ~ i~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ' ~ ~ ~ a ~ ~ ~ ~ ~ ,~, ~ ~ , ~ ~ S ~= 3 >= >~= =~= ~ ~ >= ~ A A A ~ C~J A C~ t_ C ~I ~ I C~ ~ 5 LO ~ ~ C~ ~ b_ _ / ~ / \ / \ ~ ~ / \ C~ ~ ~C~ _ ~ ) _ C ~_ _ _ ~4 ~ ~ 4= ~ .~ .~ .~ ~ ~ ~ ~ .~ .~ .au . b.0 b4 b.0 = = b4 ~ b4 ~ ~ ~: ~: ~ ~ ~0 ~0 ~ bC C~ C~ CN] ~ ~0 ~0 b4 bC ~ ~ ~ c~ ~ CO ~ co O C~ ~ C~ b.0 O O _ ~ ~ _ _ CO C~ C~ o 4= 4= 0 . ~ ~ - ._ ._ ~ b.0 bO bC b4 o ~ L~ _ _ oO ~4 C~ ~ ~ ~ ~ ~ ~8 ~ ~ ~ ~ o o ~ ~ ~ ~ ~ ~ o ~ ~ _ ~ _ _ ~ C~ ~ ~ ~ ~ CO ~U ~ _ o o o ~ - ~ O ~ - 4 ~ U: o ~4 0 1 0 C~ C~ ~ C~ ~ ~ C~ C~ ~C~ ~o o o U:} CiD U:) C~0 C :} CD C~0 CO C~0 C~0 - C~ o o - C~ CO .W~ o ~ ~ ~ a~ o ~v a.) ~ O ~C ~C~= - - =' . ~ . ~ . C.) . C) . ~ . ~ . ~ ~ ~ . ~O O ~ f ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~0= 0" 0= 0~ 0= =-~ ~ ~ ~ = ~a ~ . _ S- o . ~

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40 Vitamin Tolerance of Animals Jacob, 1974) have been questioned, and the potentiation of a vitamin By deficiency by high levels of ascorbic acid appears to be unlikely (Hogenkamp, 1980~. Neverthe- less, there seem to be some negative side effects to ex- cessive amounts of ascorbic acid intakes, although there is no information indicating lethality. An LD50 value has not been determined for any laboratory animal species. There is very little information on any toxicity signs associated with excess ascorbic acid intake in domestic animals. In studies conducted on dogs, Leveque (1969) reported allergic types of reaction in the mouth. These signs disappeared when the level of ascorbic acid intake by the dogs was reduced. However, this observation was incidental, and the study was not controlled. The only study conducted on mink suggested that these ani- mals may be very sensitive to high levels of ascorbic acid (Ender and Helgebostad, 19721. Intakes of 100 to 200 mg of ascorbic acid/kg of BW per day produced a pro- nounced anemia in pregnant females with a subsequent significant reduction in the number and size of kits. Vir- tually no studies have been conducted on other species of domestic animals to determine the levels of ascorbic acid that may be toxic or the symptoms or signs of ascor- bic acid toxicity. Concentrations in Tissues Ascorbic acid has a wide distribution in animal tissues. In laboratory animals, high concentrations of ascorbic acid are normally found in glandular tissues such as the pituitary, salivary, and adrenal glands with the adrenal glands having the greatest concentration (Kirk, 1962; Hammarstroem, 1966; Hornig, 1975~. The brain, liver, lungs, pancreas, and spleen normally have intermediate to high concentrations. Because these organs are larger than glandular tissues, their contribution of ascorbic acid to the total amount in the body is far greater. With the exception of fish, very few studies with do- mestic animal species have been concerned with the effect of excessive levels of ascorbic acid on tissue. In studies on catfish, salmon, and trout, the ascorbic acid concentrations in the liver and head kidney increased in relation to dietary levels of the vitamin, eventually showing a plateau beyond which there were no further increases (Halver et al., 1969; Hilton et al., 1978; Lim and Lovell,1978~. In contrast, muscle ascorbic acid con- centrations were not affected by increases in the dietary intakes of the vitamin (Hilton et al., 1979~. Similarly, studies on chickens have indicated that muscle ascorbic acid concentrations remained constant when the dietary level of ascorbic acid was varied (Dorr and Nockels, 1971~. In virtually all other domestic animal studies, only plasma ascorbic acid levels have been reported. They seldom have been related to differences in ascor- bic acid intake levels. PRESUMED UPPER SAFE LEVELS As indicated in Table 10, there is insufficient informa- tion to determine maximum tolerance levels of ascorbic acid for most domestic animals species. At this time, the most complete information is available only for the chicken. Dietary intakes up to 3,300 mg of ascorbic acid/ kg of feed do not appear to affect the chicken adversely in prolonged growth studies of more than 60 days (Her- rick and Nockels, 1969; Chen and Nockels, 1973; Nock- els, 1973; Schmeling and Nockels, 1978~. Similarly, research on swine (Brown et al., 1971, 1975; Sandholm et al., 1979; Chavez, 1983) and fish (Lanno et al., 1985) has indicated that dietary intakes of as much as 10 g of ascorbic acid/kg of feed do not adversely affect growth. However, studies on swine have been of much shorter duration (less than 60 days) than studies on chickens or trout. In addition, intakes of 0.5 and 3.0 g ascorbic acid/ day in cats and dogs, respectively, do not appear to af- fect these animals adversely in short-term studies (Belfield, 1967; Edwards, 1968; Leveque, 1969; Vaananen and Wekman, 19791. Long-term studies are required. There is much more information concerning the safe and apparently toxic ascorbic acid intake levels in labo- ratory animal species (Table 10~. Some of the results, such as those with rats and guinea pigs, are contradic- tory, however. Nevertheless, it appears that levels up to 1 g of ascorbic acid/kg of feed in rat and guinea pig diets do not adversely affect the animals' growth. Further studies are warranted. SUMMARY 1. Excess ascorbic acid intakes in humans and labora- tory animals have been reported to produce a variety of toxic signs or symptoms including allergic responses, oxaluria, uricosuria, and interference with mixed- function oxidase systems. 2. Despite the variety of toxic signs in laboratory ani- mals due to excessive intakes of ascorbic acid, there has been no associated lethality reported. 3. There is insufficient information on the tolerance and toxicity of ascorbic acid in most domestic animals. 4. In growth studies of varying lengths, ascorbic acid intakes of 3.3 g/kg of feed for chickens and 10 g/kg of feed for swine and trout do not appear to affect ad- versely the growth of these animals. Studies on other domestic animals are needed.

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Ascorbic Acid 41 REFERENCES Baker, E. M., J. C. Saari, and B. M. Tolbert. 1966. Ascorbic acid metabolism in man. Am. J. Clin. Nutr. 19:371. Bauernfeind, J. C. 1982. Ascorbic acid technology in agricultural, pharmaceutical, food and industrial applications. Pp. 395-497 in Ascorbic Acid: Chemistry, Metabolism and Uses, P. A. Seib and B. M. Tolbert, eds. Adv. Chem. Ser. Vol. 200. Washington, D.C.: American Chemical Society. Belfield, W. O. 1967. Vitamin C in treatment of canine and feline distemper complex. Vet. Med. Small Anim. Clin. 62:345. Brandt, T. M., C. W. Deyve, and P. A. Sieb.1985. Alternate sources of vitamin C for channel catfish. Prog. Fish Cult. 47:55. Bray, D. L., and G. M. Briggs.1984. Decrease in bone density in young male guinea pigs fed high levels of ascorbic acid. J. Nutr. 114:920. Brown, R. G., V. I). Sharma, L. G. Young, and J. G. Buchanan-Smith. 1971. Connective tissue metabolism in swine. II. Influence of en- ergy level and ascorbate supplementation on hydroxyproline excre- tion. Can. J. Anim. Sci. 51:439. Brown, R. G., J. G. Buchanan-Smith, and V. D. Sharma.1975. Ascor- bic acid metabolism in swine. The effects of frequency of feeding and level of supplementary ascorbic acid on swine fed various en- ergy levels. Can. J. Anim. Sci. 55:353. Burns, J. J. 1957. Missing step in man, monkey and guinea pig re- quired for biosynthesis of -ascorbic acid. Nature (London) 180:553. Burns, J. J. 1975. Overview of ascorbic acid metabolism. Pp. 5-6 in Second Conference on Vitamin C. Ann. N.Y. Acad. Sci.258. Cappa, V. 1958. Destruction of vitamin C by the bacterial flora of the rumen. Riv. Zootec. 31:199. Chatterjee, I. B., A. K. Majumber, B. K. Nandi, and N. Subramanian. 1975. Synthesis and some major functions of vitamin C in animals. Pp.24-47 in Second Conference on Vitamin C. Ann. N.Y. Acad. Sci. 258. Chavez, E. R. 1983. Supplemental value of ascorbic acid during late gestation on piglet survival and early growth. Can. J. Anim. Sci. 63:683. Chen, A. A., and C. F. Nockels.1973. The effect of dietary vitamin C, protein, strain and age on egg quality, production and serum and albumin protein of chickens. Poult. Sci. 52:1862. Chick, H. 1953. Early investigations of scurvy and the anti-scorbutic vitamin. Proc. Nutr. Soc. 12:210. Cole, C. L., R. A. Rasmussen, and F. Thorp, Jr. 1944. Dermatosis of the ears, cheeks, neck and shoulders of young calves. Vet. Med. 39:204. Cook, J. D., and E. R. Monsen.1977. Vitamin C, the common cold and iron absorption. Am. J. Clin. Nutr. 30:235. Davies, H. E. F., J. E. W. Davies, R. E. Hughes, and E. Jones. 1984. Studies on the absorption of L-xyloascorbic acid (vitamin C) in young and elderly subjects. Hum. Nutr. Clin. Nutr. 38C:463. Dorr, P. E., and C. F. Nockels. 1971. Effects of aging and dietary ascorbic acid on tissue ascorbic acid in the domestic hen. Poult. Sci. 50:1375. Edwards, W. C. 1968. Ascorbic acid for treatment of feline rhinotra- cheitis. Vet. Med. Small Anim. Clin. Ther. 63:696. Ender, F., and A. Helgebostad.1972. Iron deficiency anemia in mink. Z. Tierphysiol. Tierernaehr. Futtermittelkd., Heft 19:22. Errington, B. J.,13. S. Hodgkiss, and E. P. Jayne. 1954. Ascorbic acid in certain body fluids of horses. Am. J. Vet. Res. 3:242. Grondalin, T., and I. Hansen.1981. Effect of mega doses of vitamin C on osteochondrosis in pigs. Nord. Veterinaermed. 33:423. Grunewald, K. K., and L. K. Mitchell.1981. Serum enzyme activities in mice fed a high level of ascorbic acid. Nutr. Res. 1:393. Halver, J. E., L. M. Ashley, and R. E. Smith. 1969. Ascorbic acid requirements of coho salmon and rainbow trout. Trans. Am. Fish Soc. 98:762. Halver, J. E., R. R. Smith, B. M. Tolbert, and E. M. Baker. 1975. Utilization of ascorbic acid in fish. Pp.81-102 in Second Conference on Vitamin C. Ann. N.Y. Acad. Sci. 258. Hammarstroem, L. 1966. Autoradiographic studies on the distribu- tion of C~4-labelled ascorbic acid and dehydroascorbic acid. Acta Physiol. Scand. 70 (Suppl.289):1. Herbert, V., and E. Jacob.1974. Destruction of vitamin B,2 by ascorbic acid. J. Am. Med. Assoc. 230:241. Herrick, J. B. 1972. Vitamin nutrition of the horse. Vet. Med. Small Anim. Clin. 67:688. Herrick, J. B., and C. F. Nockels.1969. Effect of a high level of dietary ascorbic acid on egg quality. Poult. Sci. 48:1518. Hilton, J. W., C. Y. Cho, and S. J. Slinger.1978. Effect of graded levels of supplemental ascorbic acid in practical diets fed to rainbow trout. J. Fish Res. Bd. Can. 35:431. Hilton, J. W., R. G. Brown, C. Y. Cho, and S. J. Slinger. 1979. The synthesis, half-life and distribution of ascorbic acid in rainbow trout (Salmogairdneri). Can. J. Fish Aquat. Sci. 37:170. Hodson, P. V., J. W. Hilton, B. R. Blunt, and S. J. Slinger.1980. Effects of dietary ascorbic acid on chronic lead toxicity to young rainbow trout (Salmogairdneri). Can. J. Fish Aquat. Sci. 37:170. Hogenkamp, H. P. C. 1980. The interaction between vitamin B,2 and vitamin C. Am. J. Clin. Nutr. 33:1. Hornig, D.1975. Metabolism of ascorbic acid. World Rev. Nutr. Diet. 23:225. Hornig, D., and M. Frigg. 1979. Effect of age on biosynthesis of ascorbic acid in chicks. Arch. Gefluegelkd. 43:108. Hornig, D., F. Weber, and O. Wiss.1973. Site of intestinal absorption of ascorbic acid in guinea pigs and rats. Biochem. Biophys. Res. Commun. 52:168. Hornig, D., J. P. Vuilleumier, and D. Hartmann. 1980. Absorption of large, single, oral intakes of ascorbic acid. Int. J. Vit. Nutr. Res. 50:309. Jaeschke, G., and H. Keller.1982. The ascorbic acid status of horses. 4. Behaviour of intravenously applicated ascorbic acid in the serum. Berl. Muench. Tieraerztl. Wochenschr. 95:71. Kagawa, Y. 1962. Enzymatic studies on ascorbic acid catabolism in animals. I. Catabolism of 2,3-diketogulonic acid. J. Biochem. 51:134. Kagawa, Y., Y. Mano, and N. Shimayino. 1960. Biodegradation of dehydro-2-ascorbic acid; 2,3-diketo-~-aldenic decarboxylase from rat liver. Biochim. Biophys. Acta 43:348. Kallner, A., D. Hartmann, and D. Hornig.1977. On the absorption of ascorbic acid in man. Int. J. Vit. Nutr. Res.47:383. Keith, M. O., B. G. Shah, E. A. Nera, and O. Pelletier. 1974. The effects of high ascorbic acid and iron intake on the renal excretion of oxalate, calcium, and iron and on the kidney of rats. Nutr. Rep. Int. 10:357. Kirk, J. E. 1962. Variations in the tissue contents of vitamins and hormones. IV. Ascorbic acid. Vit. Horm. (N.Y.) 20:83. Knight, C. A., R. A. Dutcher, N. B. Cuerrant, and S. I. Bechdel.1941. Utilization and excretion of ascorbic acid in the dairy cow. J. Dairy Sci.24:567. Kubler, W., and J. Gehler. 1970. Fur Kinetik der enteralen Ascorbin satire-Resorption zur Berechnung nicht dosisproportionaler Re- sorptionsrorgange. Int. Z. Vit. Forschung. 40:442. Lanno, R. P., J. W. Hilton, and S. J. Slinger.1985. The effect of ascor- bic acid on dietary copper toxicity in rainbow trout. Aquaculture 49:269. Leveque, J. I. 196'9. Ascorbic acid in treatment of the canine distem- per complex. Vet. Med. Small Anim. Clin. 64:997. Lewin, S. 1974. High intake of vitamin C in relation to adenosine

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42 Vitamin Tolerance of Animals 3':5'-cyclic monophosphate and guanosine 3':5'-cyclic monophos- phate concentrations and to blood sugar concentrations. Biochem Soc. Trans. 2:922. Lim, C., and R. T. Lovell. 1978. Pathology of vitamin C deficiency syndrome in channel catfish. J. Nutr. 108:1137. Loewus, F. A., G. Wagner, and J. C. Yang. 1975. Biosynthesis and metabolism of ascorbic acid in plants. Pp. 7-23 in Second Confer- ence on Vitamin C. Ann. N.Y. Acad. Sci. 258. Loscher, W., G. Jaeschke, and H. Keller. 1984. Pharmacokinetics of ascorbic acid in horses. Equine Vet. J. 16:59. Mahan, D. C., and Z. J. Saif.1983. Efficacy of vitamin C supplementa- tion for weanling swine. J. Anim. Sci. 56:631. Marcusen, D. C., and R. W. Heninger.1976. Effect of ascorbic acid on the pituitary-thyroid system in the rat. J. Endocrinol. 70:313. Mayer, F. L., P. M. Mehrle; and P. L. Crutcher. 1978. Interactions of toxaphene and vitamin C in channel catfish. Trans. Am. Fish. Soc. 107:326. Nestor, K. E., S. P. 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