B12 ABSORPTION, KINETICS AND TRANSCOBALAMIN GENOTYPE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们研究的总体目标是利用碳-14标记的维生素B12（14 C-B12）和加速器质谱（AMS）来评估人体对维生素B12的吸收和周转，以及食物中维生素B12的生物利用度。 关于吸收和转换，我们对6名健康对照受试者给予14 C-B12（50 nCi，1.3 μ g），并采集基线和给药后的血液、尿液和粪便样本，用于AMS评估14 C-B12。 数据显示受试者之间的吸收和转换模式相对一致，包括在约3小时时首次出现14 C-B12，在6至8小时之间达到血浆峰水平，随后出现相似的血浆消除曲线。 一个令人惊讶的发现是，我们观察到尿液中的14 C水平很高（占给药剂量的30-40%），这与之前文献报道的使用57 Co标记维生素B12的研究中给药剂量的0.1-0.5%形成了直接对比。 我们假设，我们正在观察维生素B12在胃肠道中的分解，这在使用57 Co-B12时是不可能观察到的。 这一发现对维生素B12的生物利用度有潜在的影响，这些维生素B12来自药片和添加了维生素B12作为强化剂的食物。 未来的研究将集中在确定14 C-B12是否可用于诊断维生素B12吸收不良综合征（例如恶性贫血），并开发人体维生素B12吸收和周转的模型。 此外，我们将试图确定维生素B12是如何在胃肠道中分解的，以及这种分解的产物似乎出现在尿液中。

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.