Hematologic Responses and Concenrtation of Vitamin B12 in Serum and Urine following Oral Administration of Vitamin B12 without Intrinsic Factor

Abstract

Vitamin B12 in doses of 500 to 3000 µg. was given by mouth or by rectum to patients with megaloblastic anemia due to B12 deficiency and to normal subjects. Its absorption was studied by following the hematologic response and/or the changes in serum and urinary B12 concentrations by microbiologic assay with Euglena gracilis var. bacillaris. After oral doses of 1000 to 3000 µg. of B12 there was a definite but variable hematologic response in the thirty-five patients. The serum B12 concentrations, measured in eighteen of these patients, increased in the first twenty-four hours after the dose. The urinary excretion of B12 increased in fifteen out of sixteen patients, but the average amount excreted was only one quarter of that excreted after intramuscular injections producing comparable hematologic responses. The lower urinary excretion after the oral doses was associated with a lower total and uncombined B12 concentration in the serum. In the majority of patients serum B12 concentrations and urinary B12 excretion reached a maximum in the first six hours after the dose. After oral doses of 3000 µg. there was a rise in serum and urinary B12 in three out of four normal subjects. After doses of 500 µg., there was an increase in the serum B12 concentrations of two normal subjects and of one out of two patients with megaloblastic anemia, but there was no change in urinary B12 excretion. After rectal doses of 1000 or 3000 µg. there was evidence of absorption of the vitamin in seven out of eight patients with pernicious anemia.

ORAL TREATMENT OF PERNICIOUS ANEMIA WITH HIGH DOSES OF VITAMIN B12 WITHOUT INTRINSIC FACTOR

“…During recent years many reports have been published suggesting that high doses of vitamin B,, alone, administered orally, can produce a satisfactory effect on pernicious anemia (3,4,6,8,9,10,11,12,15,16,17,18,19,23,24,25,26,27). However, other investigators have not studied quantitatively how pernicious anemia patients absorb vitamin B,, from the intestine without the mediation of intrinsic factor (IF), nor have they studied the absorption process in cases of pernicious anemia with an acquired resistance to IF preparations or in other types of B1, deficiency.…”

The Relationship between Intrinsic Factor and the Intestinal Absorption of Vitamin B12

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ABSORPTION of vitamin B,, from the intestine can be studied either by following the haematological response of patients with pernicious anaemia in relapse after the oral administration of the vitamin or by following the changes in the serum B,, concentration after such trcatment (Ross, Mollin, Cox and Ungley, 1954). However, the exact amount of B,, that has been absorbed cannot be estimated by these methods.The introduction by Heinle, Welch, Scharf, Meacham and Prusoff (1952) of vitamin B,, labelled with the radioactive isotope of cobalt, 60C0, has provided a sensitive method for measuring B, , absorption.

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“…ABSORPTION of vitamin B,, from the intestine can be studied either by following the haematological response of patients with pernicious anaemia in relapse after the oral administration of the vitamin or by following the changes in the serum B,, concentration after such trcatment (Ross, Mollin, Cox and Ungley, 1954). However, the exact amount of B,, that has been absorbed cannot be estimated by these methods.…”

Studies on Free and Serum Protein‐bound Vitamin B12 by the Use of Sephadex G 25 and High Voltage Electrophoresis1

“…In serum from normal persons and patients with chronic myelocytic leukaemia, vitamin B,, bound in vivo has been found mainly in the a,-and a,-globulins (4,13,16) or in the u,-globulins only (6).…”

“…2. Spectrophotometrical analysis of the eluate fractions from the Sephadex column gave a peak at 2,800 A (protein absorption curve) in tube 8 and another peak a t 3,600 A (vitamin B,, absorption curve) in tubes [15][16]. The radioactivity in tubes No.…”