Blood, 1953, Vol. 8, No. 10, pp. 867-892.
© 1953 American Society of Hematology, Inc.
Oral Treatment of Pernicious Anemia with Small Doses of
Vitamin B12 Combined with Mucinous Materials Derived
from the Hog Stomach
GEORGE B. JERZY GLASS M.D.1 and
LINN J. BOYD M.D.1
1 Department of Medicine, New York Medical College, Flower and Fifth Avenue
Hospitals, and Research Unit, Metropolitan Hospital, New York, N. Y.
1. Twenty patients with pernicious anemia were treated under rigidly controlled conditions by administering small oral doses of vitamin B12 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 B12,
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 B12 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 B12 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 B12 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 B12.
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 B12 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
B12 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 B12, 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.
Submitted on March 16, 1953
Accepted on May 1, 1953
