B12 ABSORPTION, KINETICS AND TRANSCOBALAMIN GENOTYPE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall goal of our research is to utilize carbon-14 labeled vitamin B12 (14C-B12) and accelerator mass spectrometry (AMS) to assess the absorption and turnover of vitamin B12 in humans, as well as the bioavailability of vitamin B12 from foods. With respect to absorption and turnover, we have dosed 6 healthy control subjects with 14C-B12 (50 nCi, 1.3 ¿g) and collected baseline and post-dose blood, urine, and stool samples for assessment of 14C-B12 by AMS. The data show relatively consistent patterns of absorption and turnover among the subjects, including first appearance of 14C-B12 in the plasma at about 3 hours, peak plasma levels between 6 and 8 hours, followed by similar plasma elimination curves. A surprising finding has been our observation of high levels of 14C in the urine (30-40% of the administered dose), which is in direct contrast to previous literature reports of 0.1-0.5% of the administered dose in studies using 57Co-labeled vitamin B12. We have hypothesized that we are observing breakdown of the vitamin B12 in the gastrointestinal track that was not possible to observe when using 57Co-B12. This finding has potential implications for the bioavailability of B12 from pills and from foods to which vitamin B12 has been added as a fortificant. Future studies will focus on determining if 14C-B12 can be used to diagnose vitamin B12 malabsorption syndromes (e.g. pernicious anemia) and developing a model for vitamin B12 absorption and turnover in humans. In addition, we will attempt to determine how vitamin B12 is broken down in the gastrointestinal tract and what are the products of this breakdown that seem to be appearing in the urine.