Metabolic Interrelations between Gastric Intrinsic Hematopoietic Factor and Vitamin B₁₂: II. Further Assays of Vitamin B₁₂ in Blood and Urine of Patients with Pernicious Anemia and Following Total Gastrectomy by Means of Escherichia coli mutant and Euglena gracilis Technics

The concentration of vitamin B₁₂ in blood serum and its excretion in the urine were assayed by the E. coli mutant technic in two patients after total gastrectomy and by use of the more sensitive Euglena gracilis method in four cases of pernicious anemia in relapse and 1 case of well controlled nutritional macrocytic anemia.

Following parenteral administration of 100 µg. vitamin B₁₂ intramuscularly to two patients with total gastrectomy, much higher blood levels were observed within the first few hours than those reported by others under similar circumstances in normals.

Following oral administration of vitamin B₁₂ together with a potent intrinsic factor concentrate from hog stomach, a rise in blood levels of vitamin B₁₂ was observed in patients with pernicious anemia.

The normal serum levels of vitamin B₁₂ could not be maintained, however, for the entire duration of the oral treatment, in spite of the apparent hematologic and clinical remission. The urinary output of vitamin B₁₂ was in all instances less than 0.5 per cent of the total dose of vitamin B₁₂ ingested during the experimental period, in spite of an optimal or suboptimal hematopoietic response obtained. A similar situation existed in patients with total gastrectomy, as well as in the patient with controlled macrocytic nutritional anemia, when vitamin B₁₂ was ingested alone or with intrinsic factor concentrate.

The intensity of the obtained hematopoietic response in patients with pernicious anemia indicates the absorption of much larger amounts of vitamin B₁₂ from the intestine than is indicated by the total urinary output of vitamin B₁₂; therefore the anchorage and retention of a large part of vitamin B₁₂ in the storage depots of the body after its absorption from the intestine must occur.

A sharp increase in the urinary output of vitamin B₁₂ was observed during or immediately following the hematopoietic response in all patients with pernicious anemia treated orally with vitamin B₁₂ and intrinsic factor concentrate, i.e., coincident with or immediately following the reticulocyte peak in blood. Similar observation was reported by the authors in the previous series of investigations. Of many possible interpretations of this finding, the most plausible appears to be the metabolic release of free vitamin B₁₂ from its complex binding in the body during hyperactivity of the hematopoietic organs and its escape through the kidneys.