1. The effect of the administration of choline chloride has been observed in 10 cases of megaloblastic anemia of various types.
2. Choline was without effect in a case of untreated Addisonian pernicious anemia which subsequently responded to parenteral liver therapy.
3. Choline was also without effect in a case of nutritional megaloblastic anemia, in a case of megaloblastic anemia of pregnancy, and in two cases of megaloblastic anemia associated with the sprue syndrome. All these cases had proved refractory to injections of potent liver extract before the choline was given, and all responded to subsequent oral liver or folic acid therapy.
4. A significant erythropoietic response to choline occurred in two cases resembling Addisonian pernicious anemia which were refractory to parenteral liver extracts.
Secondary responses followed the administration of choline in two other cases of Addisonian pernicious anemia and in a case of megaloblastic anemia of pregnancy, all of which had already responded to injections of liver extract.
5. The significance of these observations is discussed. It is concluded that choline possesses no direct erythropoietic activity, but that under certain circumstances it may potentiate the effect of liver extracts.
It is suggested that refractory megaloblastic anemias may be divided into two groups. In one, represented by well known syndromes associated with defective absorption or pregnancy, the lack of response to parenteral liver extracts is not corrected by choline. In the other, represented by two cases simulating Addisonian pernicious anemia, choline is effective in overcoming, partially or completely, the refractoriness to parenteral liver therapy. Consideration is given to the view that the refractoriness of this group results from hepatic dysfunction.
6. The most satisfactory method of administering choline probably consists of intravenous injections in daily doses of 1 gram. Larger doses given intravenously are frequently accompanied by unpleasant side effects, while oral administration appears to be relatively less effective.
7. It seems unlikely that choline will be of practical value in the treatment of refractory megaloblastic anemias, for which oral liver preparations provide the most certain and effective treatment. It is possible, however, that choline may be of use in cases complicated by severe hepatic disease.
Acknowledgment: We wish to thank Dr. L. D. W. Scott for permission to include his patient (case 10) in our series.