The Disappearance of Cobalamin Absorption Testing: A Critical Diagnostic Loss

Traditionally, the bioavailability of vitamin B-12 (B12) from in vivo labeled foods was determined by labeling the vitamin with radiocobalt (57Co, 58Co or 60Co). This required use of penetrating radioactivity and sometimes used higher doses of B12 than the physiological limit of B12 absorption. The aim of this study was to determine the bioavailability and absorbed B12 from chicken eggs endogenously labeled with 14C-B12 using accelerator mass spectrometry (AMS). 14C-B12 was injected intramuscularly into hens to produce eggs enriched in vivo with the 14C labeled vitamin. The eggs, which provided 1.4 to 2.6 μg of B12 (~1.1 kBq) per serving, were scrambled, cooked and fed to 10 human volunteers. Baseline and post-ingestion blood, urine and stool samples were collected over a one-week period and assessed for 14C-B12 content using AMS. Bioavailability ranged from 13.2 to 57.7% (mean 30.2 ± 16.4%). Difference among subjects was explained by dose of B12, with percent bioavailability from 2.6 μg only half that from 1.4 μg. The total amount of B12 absorbed was limited to 0.5–0.8 μg (mean 0.55 ± 0.19 μg B12) and was relatively unaffected by the amount consumed. The use of 14C-B12 offers the only currently available method for quantifying B12 absorption in humans, including food cobalamin absorption. An egg is confirmed as a good source of B12, supplying approximately 20% of the average adult daily requirement (RDA for adults = 2.4 μg/day).

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Cobalamin absorption and hematologic status after two types of gastric surgery for obesity

American Journal of Hematology ◽

10.1002/ajh.2830420113 ◽

1993 ◽

Vol 42 (1) ◽

pp. 63-66 ◽

Cited By ~ 18

Author(s):

Charles E. Yale ◽

Paul N. Gohdes ◽

Robert F. Schilling

Keyword(s):

Gastric Surgery ◽

Surgery For Obesity ◽

Cobalamin Absorption

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Intrinsic factor-mediated intestinal absorption of cobalamin in the dog

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1981.241.4.g294 ◽

1981 ◽

Vol 241 (4) ◽

pp. G294-G299 ◽

Cited By ~ 2

Author(s):

G. Marcoullis ◽

S. P. Rothenberg

Keyword(s):

Intestinal Absorption ◽

Intrinsic Factor ◽

Physicochemical Analysis ◽

Significant Fraction ◽

Receptor Protein ◽

Ileal Mucosa ◽

Membrane Bound ◽

Triton X ◽

Selective Accumulation ◽

Cobalamin Absorption

The purpose of these studies was to determine whether gastric intrinsic factor and the ileal intrinsic factor receptor participate in the process of cobalamin absorption in the dog. Physicochemical analysis of gastrointestinal fluids and mucosal extracts obtained 3-5 h after cyano[57Co]-cobalamin was fed to dogs demonstrated that 1) all cyano-[57Co]cobalamin became bound to proteins during intraluminal transport; and 2) mucosal cyano[57Co]cobalamin in the extract of the ileal mucosa was bound to intrinsic factor, to intrinsic factor coupled to receptor protein, and to proteins with properties similar to R protein and transcobalamin II. A significant fraction of the cyano[57Co]cobalamin in the mucosal extract was membrane bound and, upon solubilization with Triton X-100, was found to contain immunoreactive intrinsic factor that, however, could no longer couple to the isolated receptor. The formation of the complex of cobalamin with intrinsic factor and the receptor protein and the selective accumulation of cobalamin in the ileum indicate that the intrinsic factor-mediated mechanism for absorption of this vitamin is active in the dog.

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Genetic Evidence of an Accessory Activity Required Specifically for Cubilin Brush-Border Expression and Intrinsic Factor-Cobalamin Absorption

Blood ◽

10.1182/blood.v94.10.3604.422k22_3604_3606 ◽

1999 ◽

Vol 94 (10) ◽

pp. 3604-3606 ◽

Cited By ~ 37

Author(s):

Danbin Xu ◽

Renata Kozyraki ◽

Thomas C. Newman ◽

John C. Fyfe

Keyword(s):

Brush Border ◽

Genetic Basis ◽

Intrinsic Factor ◽

Canine Model ◽

Renal Tubules ◽

Locus Heterogeneity ◽

High Identity ◽

Protein Reabsorption ◽

Cobalamin Absorption ◽

Cobalamin Malabsorption

Cubilin is a high molecular weight multiligand receptor that mediates intestinal absorption of intrinsic factor-cobalamin and selective protein reabsorption in renal tubules. The genetic basis of selective intestinal cobalamin malabsorption with proteinuria was investigated in a canine model closely resembling human Imerslund-Gräsbeck syndrome caused by cubilin mutations. CanineCUBN cDNA was cloned and sequenced, showing high identity with human and rat CUBN cDNAs. An intragenic CUBN marker was identified in the canine family and used to test the hypothesis of genetic linkage of the disease and CUBN loci. Linkage was rejected, indicating that the canine disorder resembling Imerslund-Gräsbeck syndrome is caused by defect of a gene product other than cubilin. These results imply that there may be locus heterogeneity among human kindreds with selective intestinal cobalamin malabsorption and proteinuria and that normal brush-border expression of cubilin requires the activity of an accessory protein.

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