THE FOLIC ACID COMPLEX 



anaemia had been successfully treated with folic acid ; 50 mg. given 

 intravenously resulted in an increase in the red blood cells, whilst 20 

 mg. daily for eighteen days gave a still bigger increase. Nine patients 

 given 50 mg. by mouth twice daily for twenty days also responded 

 with a reticulocyte peak and an increase in red blood cells and haemo- 

 globin. The patients were maintained satisfactorily on 100 mg. 

 orally twice a week. Total amounts ranging from 2 to 4-5 g. were 

 used. Cases of sprue, nutritional anaemia of pregnancy and pellagra 

 also responded satisfactorily, and the cases showed the same striking 

 increase in strength, vigour and appetite as with liver therapy.* 

 Iron-deficiency anaemia, aplastic anaemia and leukaemia did not 

 respond. 



Support for these initial results was quickly forthcoming. Two 

 cases of Addisonian pernicious anaemia responded to 30 and 100 mg., 

 and one case of macrocytic anaemia of non-tropical sprue to 20 mg. ; ^ 

 two cases of tropical sprue were improved by 15 mg.^ given intra- 

 venously, whilst other cases were restored almost to normal by 100 

 mg. given orally twice daily. "^ Macrocytic anaemias of infancy, in 

 which the bone marrow showed megaloblastic changes and the presence 

 of abnormal yoimg granulocytes of the type found in pernicious 

 anaemia, were cured by daily oral administration of folic acid, but it 

 was ineffective in all other forms of megaloblastic anaemia.^ 



A case of tropical sprue was reported ^ in which a rapid response 

 to synthetic folic acid was obtained with a dose of only 10 mg. per 

 day for five days although the case had previously failed to respond 

 to liver extract. Similarly, satisfactory responses were obtained ^^ in 

 cases of pernicious anaemia with 10 mg. per day given orally or paren- 

 terally. At the same time it was pointed out that folic acid was not 

 identical with the factor responsible for the anti-pernicious anaemia 

 activity of liver extracts. ^^ Indeed, such extracts contained very 

 little pteroylglutamic acid ^^ and the small amounts present were not 

 correlated with anti-anaemia activity.^^, i3 The rate of bone-marrow 

 changes following a single oral dose of 50 mg. of folic acid was equal to 

 that produced by intramuscular injection of liver extract. ^^ T. D. 

 Spies ^^ reported successful results in nutritional anaemia, in the macro- 

 cytic anaemias of pregnancy, pellagra and sprue as well as in per- 

 nicious anaemia ; a daily dose of 10 mg. produced the maximum 

 haemopoietic response. 



In spite of these striking claims, however, a note of caution began 

 to appear in some of the subsequent publications, drawing attention 

 to the limitations of the new agent. It gradually became clear, in 

 fact, that folic acid was inferior in many respects to liver extracts. 

 Difficulty was experienced, for example, in maintaining pernicious 

 anaemia patients on folic acid alone. ^^ Again, synthetic folic acid 



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