Folic acid deficiency has been produced experimentally in many animal species, with a macrocytic anemia (megaloblastic anemia) and leucopenia (a reduced number of white blood cells) a consistent finding. Tissues that have a rapid rate of cell growth or tissue regeneration, such as epithelial lining of the gastrointestinal tract, epidermis and bone marrow, are principally affected (Hoffbrand, 1978).
Until recently folic acid deficiency in swine had only been produced by the simultaneous feeding of sulfa drugs. Deficiencies were not observed when young pigs were fed only purified diets or natural diets low in folic acid alone (Johnson et al., 1948), indicating that intestinal synthesis was adequate to meet needs. Feeding a purified diet containing 2% sulfasuxidine to weanling pigs resulted in reduced gains and alopecia (Cartwright and Wintrobe, 1949). The pigs also developed a mild normochromic, normocytic anemia; in bone marrow there was a decrease in the ratio of leukocytes to erythrocytes and an increase in the number of immature nucleated red blood cells. Positive response was obtained after supplementation with folic acid. Cunha et al. (1948) found that folic acid was needed for normal hematopoiesis with eight-week-old pigs fed a purified diet for 21 weeks with sulfasuxidine. A normocytic anemia resulted that was prevented by folic acid, whereas a more severe anemia was produced by using a crude folic acid antagonist. A combination of folic acid and biotin was more effective than folic acid in counteracting the anemia. Lindemann and Kornegay (1986b) reported that combination of the antibiotic mixture ASP 250 (includes chlortetracycline, sulfamethazine and penicillin) and folic acid in a corn-soybean meal diet increased gains and feed consumption, with no effect of either alone.
More severe deficiency signs that responded to folic acid supplementation were induced by feeding diets containing a sulfonamide and a folic acid antagonist (Welch et al., 1947). Under such circumstances, pigs became listless, had a reduced growth rate and developed diarrhea. Hematologic manifestations were severe macrocytic anemia, leukopenia with a more marked reduction in the number of polymorphonucleocytes and mild thrombocytopenia. Cartwright et al. (1952) reported a combined folic acid and vitamin B12 deficiency for pigs receiving a purified soybean protein diet that included a folic acid antagonist. Growth rate was reduced and macrocytic anemia, leukopenia and neutropenia developed with erythroid hyperplasia of the bone marrow. Folic acid supplementation immediately resulted in a normal blood and bone marrow profile but growth was decreased and blood parameters subsequently relapsed.
In addition to sulfa drugs and other folic acid antagonists, moldy feeds can increase the need for the vitamin. In seven swine feeding trials involving more than 1,000 pigs fed corn with mold infestation, additional folic acid increased growth rate up to 15% and improved feed efficiency up to 9% (Purser, 1981). Folic acid supplementation was of no value when normal corn was fed.
Recently, inadequate folic acid has been associated with suboptimal reproductive performance of sows. A dramatic decrease in serum folic acid concentrations was observed during early and mid-gestation that may be associated in part with embryonic mortality (Matte et al., 1984a). In a separate trial, folic acid was administered intramuscularly according to a schedule that maintained serum folic acid concentrations at approximately the same level between weaning and 60 days of gestation (Matte et al., 1984b). Average live litter size was 12 piglets per litter for sows receiving folic acid and flushing treatments as compared with 10.5 piglets for sows without any treatment. In another study, addition of 5.0 mg folic acid per kg (2.3 mg per lb) of diet improved survival rate of fetuses during early gestation, 62.2% versus 55.1% compared to those not receiving folic acid (Tremblay et al., 1989). Lindemann and Kornegay (1989) found the number of matings required per female farrowing was less with folic acid supplements (1.07 versus 1.16 for controls). Friendship and Wilson (1991) suggested that folic acid from natural feedstuffs plus the current low level of supplemental folic acid typically used may not be sufficient to maximize reproductive performance of sows. These authors utilized a 400-sow commercial herd experiencing small litter size in their experiment. When 25 mg of folic acid was injected at the time of breeding and at one week later, and if only parities 3 to 5 were analyzed, the litter size was improved by one pig per litter over that of the control sows. Additional research is required to determine if supplemental dietary folic acid will reduce embryonic death loss under differing management systems to improve overall efficiency of production (i.e., to optimize pig survival and litter size).
