Division of Nutritional Sciences, Cornell University, Ithaca, NY.
Division of Nutritional Sciences, Cornell University, Ithaca, NY; Department of Health and Nutrition Sciences, Brooklyn College, Brooklyn, NY.
J Nutr Biochem. 2019 Oct;72:108210. doi: 10.1016/j.jnutbio.2019.07.001. Epub 2019 Jul 8.
Despite participation in overlapping metabolic pathways, the relationship between choline and vitamin B-12 has not been well characterized especially during pregnancy. We sought to determine the effects of maternal choline supplementation on vitamin B-12 status biomarkers in human and mouse pregnancy, hypothesizing that increased choline intake would improve vitamin B-12 status. Associations between common genetic variants in choline-metabolizing genes and vitamin B-12 status biomarkers were also explored in humans. Healthy third-trimester pregnant women (n=26) consumed either 480 or 930 mg choline/day as part of a 12-week controlled feeding study. Wild-type NSA and Dlx3 heterozygous (Dlx3+/-) mice, which display placental insufficiency, consumed a 1×, 2× or 4× choline diet and were sacrificed at gestational days 15.5 and 18.5. Serum vitamin B-12, methylmalonic acid (MMA) and homocysteine were measured in all samples; holotranscobalamin (in humans) and hepatic vitamin B-12 (in mice) were also measured. The 2× choline supplementation for 12 weeks in pregnant women yielded higher serum concentrations of holotranscobalamin, the bioactive form of vitamin B-12 (24%, P=.01). Women with genetic variants in choline dehydrogenase (CHDH) and betaine-homocysteine S-methyltransferase (BHMT) had higher serum MMA concentrations (31%, P=.03) and lower serum holotranscobalamin concentrations (34%, P=.03), respectively. The 4× choline dose decreased serum homocysteine concentrations in both NSA and Dlx3+/- mice (36% and~43% respectively, P≤.015). In conclusion, differences in choline supply due to supplementation or genetic variation modulate vitamin B-12 status during pregnancy, supporting a functional relationship between these nutrients.
尽管胆碱和维生素 B-12 参与重叠的代谢途径，但它们之间的关系，尤其是在怀孕期间，尚未得到很好的描述。我们试图确定母体胆碱补充对人类和小鼠妊娠中维生素 B-12 状态生物标志物的影响，假设增加胆碱的摄入会改善维生素 B-12 状态。在人类中还探索了胆碱代谢基因中的常见遗传变异与维生素 B-12 状态生物标志物之间的关联。健康的妊娠晚期妇女（n=26）作为为期 12 周的对照喂养研究的一部分，分别摄入 480 或 930 mg 胆碱/天。野生型 NSA 和 Dlx3 杂合子（Dlx3+/-）小鼠，表现出胎盘功能不全，消耗 1×、2×或 4×胆碱饮食，并在妊娠第 15.5 和 18.5 天被处死。所有样本均测量血清维生素 B-12、甲基丙二酸（MMA）和同型半胱氨酸；人类测量全转钴胺素（holotranscobalamin），小鼠测量肝脏维生素 B-12。孕妇补充 12 周 2×胆碱可使血清全转钴胺素浓度升高，维生素 B-12 的生物活性形式（约 24%，P=.01）。胆碱脱氢酶（CHDH）和甜菜碱-同型半胱氨酸 S-甲基转移酶（BHMT）中的遗传变异妇女血清 MMA 浓度较高（31%，P=.03），血清全转钴胺素浓度较低（34%，P=.03）。4×胆碱剂量可降低 NSA 和 Dlx3+/- 小鼠的血清同型半胱氨酸浓度（分别约为36%和43%，P≤.015）。总之，由于补充或遗传变异导致的胆碱供应差异会调节妊娠期间的维生素 B-12 状态，支持这些营养素之间存在功能关系。
