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) consistent findings. 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). When megaloblastic anemia is observed in dogs and cats, it is more commonly associated with folic acid deficiency caused by intestinal malabsorption syndromes, a defective diet, folic acid antagonists or an increase in folic acid requirement due to blood loss or hemolysis.
For some animals, such as the chick, guinea pig, monkey and pig, the presence of adequate amounts of folic acid in the diet is essential, and deficiency signs can readily be induced by feeding a diet deficient in the vitamin. In other animals, including the dog, cat and rat, folic acid produced by the intestinal microflora is usually adequate to meet requirements. Consequently, deficiency signs do not develop unless an intestinal antiseptic is also included in the diet to depress bacterial growth. Folic acid deficiency has been described in dogs and cats but usually only when semi-purified diets were fed in the presence of antibiotics. It is likely that most of the daily requirement for folic acid is met by bacterial synthesis in the intestine.
Assessment of nutritional status of folic acid can involve dietary evaluation, clinical signs, response to supplementation, and laboratory analysis. In folic acid deficiency, formiminoglutamic acid (FIGLU), formed as an intermediate in degradation of histidine, can no longer be transformed completely into glutamate and formiminotetrahydrofolic acid, and is therefore excreted in urine. This excretion is suitable as a biochemical criterion for diagnosis of folic acid deficiency, appearing at an early stage of deficiency. Because the liver contains a high percentage of stored folic acid, concentration in this organ would serve as a folic acid status indicator. On low-folic acid diets, liver concentrations are depleted in a few months. Clinical signs of folic acid deficiency are extremely variable and are less precise than laboratory analysis to confirm a deficiency. A protocol of folic acid depletion-repletion of rats, followed by growth, liver, serum, and erythrocyte folic acid measurements, has been successful in evaluating the bioavailability of folic acid food sources (Clifford et al., 1990; 1991).
Amyes et al. (1975) determined the folic acid concentrations of cat erythrocytes, plasma and liver and found that these values declined from birth to 32 days. Thenen and Rasmussen (1978) reported a marked depletion of plasma and liver folic acid as weanling kittens were fed a folic acid-deficient diet.
