Maternal choline supplementation alters vitamin B-12 status in human and murine pregnancy
2019
King, Julia H | Kwan, Sze Ting Cecilia | Bae, Sajin | Klatt, Kevin C | Yan, Jian | Malysheva, Olga V | Jiang, Xinyin | Roberson, Mark S | Caudill, Marie A.
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. Wildtype NSA and Dlx3 heterozygous (Dlx3+/−) mice, which display placental insufficiency, consumed a 1X, 2X or 4X 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. 2X 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 4X 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.
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