THE FOLIC ACID COMPLEX 



were ineffective in the vitamin M-deficient monkey, ^^ rat 3* and 

 chick. ^^ Furthermore, folic acid does not appear to be a precursor of 

 the anti-pernicious anaemia factor, since the latter does not contain 

 either a pterine nucleus or an aromatic amine such as ^-aminobenzoic 

 acid (page 533). 



Patients with macrocytic anaemia (nutritional), sprue, pernicious 

 anaemia of pregnancy and idiopathic refractory megaloblastic anaemia 

 are, however, refractory to the injection of potent purified liver 

 extracts, despite the presence of a megaloblastic bone-marrow. Such 

 patients respond to orally administered whole liver, proteolysed liver, 

 liver extract or folic acid. According to L. S. P. Davidson and 

 R. H. Girdwood ^^ these types of anaemia are due not to defective 

 production of the factor responsible for liberating free folic acid from 

 the conjugated form, but to the absence of conjugated folic acid either 

 as the result of a dietary deficiency or of failure to absorb folic acid 

 from the food. Hence injections of liver extract fail to cure these 

 conditions, whereas free folic acid is effective. The efficacy of proteo- 

 lysed or oral liver extracts may be due to the presence of folic acid 

 conjugates. 



Thus the most satisfactory theory that can be put forward at the 

 present time to account for the different forms of anaemia is that 

 free pteroylglutamic acid is essential for haemopoiesis, though not for 

 the maintenance of a healthy central nervous system. If pteroyl- 

 glutamic acid conjugates are absent from the diet or are not absorbed, 

 a nutritional anaemia will result. If, on the other hand, they are 

 present but the gastric juice is defective in apoerythrein, the absorp- 

 tion of vitamin B^g from the food is impaired and the conversion of 

 folic acid conjugates into free folic acid and certain other transforma- 

 tions not at present characterised do not take place and pernicious 

 anaemia supervenes. Folic acid or its conjugates given by mouth 

 cure nutritional anaemias but not pernicious anaemia, whilst free 

 folic acid but not its conjugates cure the haematological but not the 

 neurological symptoms of pernicious anaemia. Vitamin B^g has no 

 effect on nutritional anaemia, because in this condition the liver 

 already has adequate supplies, whereas it is effective in pernicious 

 anaemia by injection because it is then immediately available for 

 effecting, amongst other reactions, the liberation of pteroylglutamic 

 acid. It is ineffective by mouth because it requires apoerythrein 

 before it can be absorbed and stored in the liver. 



The theory that liver extracts contain a factor that liberates free 

 folic acid from conjugates stored in the body, thus initiating the haemo- 

 poietic response, is not accepted by all workers, however. For 

 instance, Suarez et al.^^ claimed that West Indian sprue responded to 

 treatment with conjugates as well as to free folic acid, and that some 



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