A Dual Mechanism of Vitamin B12 Plasma Absorption1

Abstract

Recent reports have described two types of plasma absorption curves following the oral administration of vitamin B1.,. With microbiologic assay methods, after massive doses of vitamin. Bs, early significant plasma levels have been found indiscriminately in both pernicious anemia patients and control subjects (1, 2). On the other hand, two independent laboratories, using radio-labeled cyanocobalamin, have successfully determined plasma absorption curves after the oral administration of only 0.46 to 1.0 microgram doses (3, 4).With these small amounts of vitamin B12 a distinctly different type of absorption curve was found in normal subjects and in pernicious anemia patients when intrinsic factor was added. This curve was characterized by little or no plasma radioactivity during the first four hours of the test and a peak concentration in the 8-to 12-hour interval. Furthermore, there was clear differentiation between control subjects and patients with pernicious anemia, because at these dosage levels the latter without added intrinsic factor showed insignificant plasma radioactivity.In this investigation plasma absorption curves were obtained in pernicious anemia patients with and without intrinsic factor, as well as in control subjects after the oral administration of test doses of radio-labeled cyanocobalamin which ranged from 0.56 to 500 micrograms. This included a dosage range not previously examined. MATERIAL AND METHODSCobalt'-labeled vitamin B. 2 used in test doses had an initial specific activity of 1,137 microcuries per mg., while that of the Cotm-labeled vitamin Bn-2 used was 893 microcuries per mg. Crystalline non-radioactive vitamin B,2 was added as necessary to make up the desired test

Human vitamin B 12 absorption measurement by accelerator mass spectrometry using specifically labeled 14 C-cobalamin

“…A single 1.5-g dose of the 14 C-B 12 was administered orally and detected by AMS as it appeared in the bloodstream. Normally, the release of B 12 from intestinal mucosa cells into the portal vein occurs Ϸ2 h after the oral consumption of the vitamin, and release into systemic circulation takes an additional 1 h (18,19). Consistent with this finding, the 14 C from the labeled B 12 appeared in the plasma of the human subject 3 h after the dose.…”

Mechanism of Intrinsic Factor Action in Everted Sacs of Rat Small Intestine*

“…A further parallel of the in vitro system with the in vivo situation is the demonstration of two separate mechanisms of vitamin B12 uptake in both. One mechanism is intrinsic factor-dependent, and plays the major role in absorption of physiologic amounts of vitamin B12 (20,21). It is this mechanism with which this report is mainly concerned.…”

“…The other mechanism appears to be a "mass action phenomenon," possibly diffusion, and is operative in bringing about the absorption of small amounts of vitamin B12. This latter mechanism is most readily observable in the human subject after the oral administration of supraphysiologic amounts of vitamin B12 (20,21). In the everted sac of rat small intestine, it may be this mechanism which produces the vitamin B12 uptake observed in controls.…”

Sequential Mechanisms in the Enhanced Absorption of Vitamin B12 by Intrinsic Factor in the Rat*

“…Thus adherence of vitamin B12 to the intestinal wall after binding to intrinsic factor may be only a preparatory step (Phase II) for subsequent -species-related transport across the intestinal wall. At any rate, there is evidence from observations in both man (16,17) and in the rat (18) that a process concerned with the absorption of vitamin B12 takes place in the intestinal wall and requires up to four hours. Species-related activity would be expected to be characteristic of a process occurring within a tissue but not necessarily upon its surface, in this case the small intestine.…”