Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans

Yan, Jian; Jiang, Xinyin; West, Allyson A.; Perry, Clifton; Malysheva, Olga; Devapatla, Srisatish; Pressman, Eva; Vermeylen, Françoise; Stabler, Sally P.; Allen, Robert H.; Caudill, Marie A.

doi:10.3945/ajcn.111.022772

Cited by 146 publications

(216 citation statements)

References 32 publications

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“…In a 12-wk feeding study examining the impact of pregnancy on biomarkers of choline metabolism, we observed alterations in the concentrations of several choline metabolites (primary endpoint variables) in pregnant (compared with nonpregnant) women including plasma depletion of choline-derived methyl donors and elevations in plasma choline (5). By using stable isotope methodology performed after our initial report (5), the current study sought to provide mechanistic insights into the underlying causes of the pregnancy-induced alterations in choline metabolism. Specifically, we measured the isotopic enrichment of choline-related metabolites in the blood and urine (primary endpoint variables) of our study participants who had consumed methyl-d9-choline during the last half of the 12-wk feeding study (5).…”

Section: Introductionmentioning

confidence: 96%

“…By using stable isotope methodology performed after our initial report (5), the current study sought to provide mechanistic insights into the underlying causes of the pregnancy-induced alterations in choline metabolism. Specifically, we measured the isotopic enrichment of choline-related metabolites in the blood and urine (primary endpoint variables) of our study participants who had consumed methyl-d9-choline during the last half of the 12-wk feeding study (5). As shown in Figure 1, methyl-d9-choline is labeled with deuterium on all 3 methyl groups, which enables assessment of the partitioning of choline (d9-choline metabolite) and its methyl groups (d3metabolites) among the various choline-related metabolic pathways (2) as well as evaluations of PC biosynthesis via the PEMT pathway (6,7).…”

Section: Introductionmentioning

confidence: 99%

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Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women

Yan

Jiang

West

et al. 2013

The American Journal of Clinical Nutrition

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women

Yan

Jiang

West

et al. 2013

The American Journal of Clinical Nutrition

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“…Methionine, betaine, choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine, in frozen liver extracts, were measured with the use of liquid chromatography-mass spectrometry (36)(37)(38). SAM and SAH, in frozen liver and whole embryo extracts, were determined with the use of liquid chromatography-mass spectrometry (39,40).…”

Section: Female Mthfd1smentioning

confidence: 99%

Moderate folic acid supplementation and MTHFD1-synthetase deficiency in mice, a model for the R653Q variant, result in embryonic defects and abnormal placental development

Christensen

Hou

Bahous

et al. 2016

The American Journal of Clinical Nutrition

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Background: Moderately high folic acid intake in pregnant women has led to concerns about deleterious effects on the mother and fetus. Common polymorphisms in folate genes, such as methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolaseformyltetrahydrofolate synthetase (MTHFD1) R653Q, may modulate the effects of elevated folic acid intake. Objectives: We investigated the effects of moderate folic acid supplementation on reproductive outcomes and assessed the potential interaction of the supplemented diet with MTHFD1-synthetase (Mthfd1S) deficiency in mice, which is a model for the R653Q variant. Design: Female Mthfd1S +/+ and Mthfd1S +/2 mice were fed a folic acid-supplemented diet (FASD) (5-fold higher than recommended) or control diets before mating and during pregnancy. Embryos and placentas were assessed for developmental defects at embryonic day 10.5 (E10.5). Maternal folate and choline metabolites and gene expression in folate-related pathways were examined. Results: The combination of FASD and maternal MTHFD1-synthetase deficiency led to a greater incidence of defects in E10.5 embryos (diet 3 maternal genotype, P = 0.0016; diet 3 embryonic genotype, P = 0.054). The methylenetetrahydrofolate reductase (MTHFR) protein and methylation potential [ratio of S-adenosylmethionine (major methyl donor):S-adenosylhomocysteine) were reduced in maternal liver. Although 5-methyltetrahydrofolate (methylTHF) was higher in maternal circulation, the methylation potential was lower in embryos. The presence of developmental delays and defects in Mthfd1S +/2 embryos was associated with placental defects (P = 0.003). The labyrinth layer failed to form properly in the majority of abnormal placentas, which compromised the integration of the maternal and fetal circulation and presumably the transfer of methylTHF and other nutrients. Conclusions: Moderately higher folate intake and MTHFD1-synthetase deficiency in pregnant mice result in a lower methylation potential in maternal liver and embryos and a greater incidence of defects in embryos. Although maternal circulating methylTHF was higher, it may not have reached the embryos because of abnormal placental development; abnormal placentas were observed predominantly in abnormally developed embryos. These findings have implications for women with high folate intakes, particularly if they are polymorphic for MTHFD1 R653Q.

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“…Notably, increased consumption of dietary choline during pregnancy can improve biomarkers of choline metabolism. For example, consumption of 930 versus 480 mg choline/day by third-trimester pregnant women led to higher circulating concentrations of several choline-derived methyl donors and restored choline partitioning between the CDP-choline and betaine pathways (which compete for choline as a substrate) to a nonpregnant state [6,19].…”

Section: Discussionmentioning

confidence: 99%

Polymorphic variants of genes involved in choline pathway and the risk of intrauterine fetal death

Drews¹,

Różycka²,

Barlik³

et al. 2017

Ginekol Pol

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Objectives: Choline and folate metabolism disturbances may be involved in the occurrence of intrauterine fetal death (IUFD). The proper activity of this metabolism could be determined by genetic variants involved in choline pathway e.g. CHKA (gene encoding choline kinase α), PCYT1A (gene encoding CCTα) and CHDH (gene encoding choline dehydrogenase). Our study aimed at determining the genotype and allele frequencies of CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms in mothers with IUFD occurrence. Material and methods:The study involved 76 mothers with IUFD occurrence and 215 mothers of healthy children. Genetic analysis was performed with the use of PCR/RFLP method. Results:The frequency of genotypes and alleles of studied polymorphisms was similar in both groups. The study revealed no association of PCYT1A, CHKA and CHDH polymorphisms in analysed groups of women. While evaluating the co-existence of analysed polymorphisms statistically significant correlation was revealed. Co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes was observed statistically more frequently in the study group than in the control group (p = 0,031). Conclusions:There is no correlation between single CHKA rs7928739, PCYT1A rs712012, PCYT1A rs7639752, CHDH rs893363 and CHDH rs2289205 polymorphisms and the incidence of intrauterine fetal death. However, revealed statistically significant difference between co-existence of CHKA rs7928739 AC/CHDH rs2289205 AA genotypes between study groups suggest the need of further analysis.

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Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans

Cited by 146 publications

References 32 publications

Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women

Pregnancy alters choline dynamics: results of a randomized trial using stable isotope methodology in pregnant and nonpregnant women

Moderate folic acid supplementation and MTHFD1-synthetase deficiency in mice, a model for the R653Q variant, result in embryonic defects and abnormal placental development

Polymorphic variants of genes involved in choline pathway and the risk of intrauterine fetal death

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