Folic acid Deficiency
A deficiency of folic acid is difficult to produce in most animals unless intestinal bacterial growth is inhibited (by feeding a sulfonamide drug or antibiotic, for example). The use of folic acid antagonists has also been widely used to produce deficiency symptoms. In monkeys a olic acid deficiency leads to a characteristic type of anemia. Rats develop anemia and eukopenia which disappear following the administration of a folic acid active substance.
Formic acid and formiminoglutamic acid excretion are increased in a deficiency state in this species. In man there results a macrocytic anemia which resembles pernicious anemia except that the nervous involvement of the latter c.ondition is absent. Vilter and co-workers pointed out that in a deficiency of folic acid coenzymes the ability of the erythrocyte precursor cells to produce DNA is impaired. Thus the cell nucleus remains young, and division is delayed while the cell grows large.
By such abnormality, there results the megaloblast, a cell with a limited supply of DNA precursors due to a deficiency offolic acid, vitamin B12 or ascorbic acid. Vitamin B12 and ascorbic acid are both required for the formation of the folic acid coenzymes. A patient with megaloblastic anemia associated with ascorbic acid deficiency was maintained on a vitamin-free diet for two weeks during which time the anemia progressed in severity. Ascorbic acid failed to prevent the progression of the condition. However, 50 ~g daily of folic acid intramuscularly initiated hematological improvement. This experiment shows that ascorbic acid has no effect on the course of the anemia unless folic acid is present. Diarrhea, gastrointestinal lesions, and other symptoms are present. Folic acid is highly effective in the treatment.
The vitamin is also effective in treating the anemia of pernicious anemia, although it is without effect on the nervous symptoms, which respond to vitamin B1Z' The sprue syndrome and some other types of anemia in humans respond to folic acid therapy. What part of the symptomatology of deficiency may be related to abnormal interconversion of glycine and serine, or to the impaired handling of formiminoglutamic acid (from histidine catabolism), or to the decreased methylation of homocysteine to yield methionine cannot be defined at this time. Folic acid labeled with tritium is given by mouth and radioactivity determined in the serum three hours later as a measure of folic acid absorption.
