Oral Treatment of Pernicious Anemia with Small Doses of Vitamin B12 Combined with Mucinous Materials Derived from the Hog Stomach

1. Twenty patients with pernicious anemia were treated under rigidly controlled conditions by administering small oral doses of vitamin B 12 in combination with intrinsic factor containing mucinous materials processed from the hog stomach. This study was undertaken in view of our earlier observation concerning the relationship of one of the mucin fractions of the human stomach (glandular mucoprotein) to Castle’s intrinsic factor. The following sources of intrinsic factor from animal stomach were used: (a) commercial gastric mucin; (b) acetic acid extracts of hog pyloric mucosa; (c) mucinous materials precipitated by acetone or by saturation with ammonium sulfate from hydrochloric acid extracts of the hog pyloric mucosa; (d) mucous fractions obtained by further fractionation in the electroconvection apparatus of the above mucinous materials precipitated with ammonium sulfate; (e) an intrinsic factor concentrate from the hog stomach in combination with small doses of vitamin B 12 , processed under the trade name of Bifacton. 2. Results obtained in this study indicate the feasibility of attaining complete clinical remission and suboptimal or optimal hematopoietic responses in patients with pernicious anemia in relapse when small daily doses (below 20 µg.) of vitamin B 12 are given orally in combination with mucinous materials processed by various technics from the hog stomach and containing intrinsic factor. The provisions are that: (1) the doses of both vitamin B 12 and intrinsic factor containing materials be adequate and optimal in regard to their mutual ratio; (2) the process involved in processing intrinsic factor containing materials not impair their activity and yield a product sufficiently concentrated. 3. The hematopoietic responses and clinical remissions obtained in six cases of pernicious anemia with Bifacton (vitamin B 12 with intrinsic factor concentrate) in different batches were uniform in our hands. The doses employed were marginal, in order to detect differences in potency, and although the reticulocyte responses were frequently suboptimal and protracted, the increases in red cells were roughly equivalent to those obtained with daily administration of approximately 1 unit of a standard oral antianemia preparation. Bifacton is supplied in strikingly smaller dosages than the standard liver or stomach oral preparations, and is fully active in a total daily oral dose of about 50 mg. of intrinsic factor concentrate with 15 µg. vitamin B 12 . 4. Preliminary studies on two patients with pernicious anemia tend to indicate that the administration of massive single oral doses of Bifacton repeated at intervals of one week may imitate even more closely the results of parenteral treatment with injectable liver concentrates or vitamin B 12 than does the administration of this concentrate in small daily doses. The single dose of Bifacton which was given once a week to one of these patients contained 150 µg. vitamin B 12 with approximately 250 mg. of intrinsic factor concentrate. Five consecutive single doses administered at intervals of from seven to ten days induced a complete clinical and hematologic remission. 5. The studies on two patients with pernicious anemia indicate that Bifacton is resistant to boiling and that it preserves its hematopoietic activity after being boiled in water for from thirty to forty-five minutes at 95 to 100°C. This suggests either that the intrinsic factor of the animal stomach becomes thermostable after the interaction in vitro with vitamin B 12 , or that the product of this binding is thermostable under conditions described. 6. The data reported here indicate that various extraction and precipitation procedures may be applied to hog stomach tissue to obtain materials which will exhibit definite intrinsic factor activity in patients with pernicious anemia. Although at present some such extracts are active orally in such small doses as from 40 to 50 mg. per day, still further refinement appears to be possible.