Choline Metabolome Response to Prenatal Choline Supplementation Across Pregnancy: A Randomized Controlled Trial
Overview
Authors
Affiliations
Pregnancy places a unique stress upon choline metabolism, requiring adaptations to support both maternal and fetal requirements. The impact of pregnancy and prenatal choline supplementation on choline and its metabolome in free-living, healthy adults is relatively uncharacterized. This study investigated the effect of prenatal choline supplementation on maternal and fetal biomarkers of choline metabolism among free-living pregnant persons consuming self-selected diets. Participants were randomized to supplemental choline (as choline chloride) intakes of 550 mg/d (500 mg/d d0-choline + 50 mg/d methyl-d9-choline; intervention) or 25 mg/d d9-choline (control) from gestational week (GW) 12-16 until Delivery. Fasting blood and 24-h urine samples were obtained at study Visit 1 (GW 12-16), Visit 2 (GW 20-24), and Visit 3 (GW 28-32). At Delivery, maternal and cord blood and placental tissue samples were collected. Participants randomized to 550 (vs. 25) mg supplemental choline/d achieved higher (p < .05) plasma concentrations of free choline, betaine, dimethylglycine, phosphatidylcholine (PC), and sphingomyelin at one or more study timepoint. Betaine was most responsive to prenatal choline supplementation with increases (p ≤ .001) in maternal plasma observed at Visit 2-Delivery (relative to Visit 1 and control), as well as in the placenta and cord plasma. Notably, greater plasma enrichments of d3-PC and LDL-C were observed in the intervention (vs. control) group, indicating enhanced PC synthesis through the de novo phosphatidylethanolamine N-methyltransferase pathway and lipid export. Overall, these data show that prenatal choline supplementation profoundly alters the choline metabolome, supporting pregnancy-related metabolic adaptations and revealing biomarkers for use in nutritional assessment and monitoring during pregnancy.
Scherbinsky K, Rasmussen B, Li B, Kong D, Ball R, Pencharz P Am J Clin Nutr. 2024; 120(4):973-983.
PMID: 39128498 PMC: 11473503. DOI: 10.1016/j.ajcnut.2024.07.034.
Enzymes of sphingolipid metabolism as transducers of metabolic inputs.
Velazquez F, Luberto C, Canals D, Hannun Y Biochem Soc Trans. 2024; 52(4):1795-1808.
PMID: 39101614 PMC: 11783705. DOI: 10.1042/BST20231442.
Obeid R, Schon C, Derbyshire E, Jiang X, Mellott T, Blusztajn J Nutrients. 2024; 16(2).
PMID: 38257153 PMC: 10820518. DOI: 10.3390/nu16020260.
Clementson M, Hurley L, Coonrod S, Bennett C, Marella P, Pascual A Neural Regen Res. 2023; 18(11):2443-2448.
PMID: 37282475 PMC: 10360112. DOI: 10.4103/1673-5374.371375.
Alldred M, Pidikiti H, Heguy A, Roussos P, Ginsberg S FASEB J. 2023; 37(6):e22944.
PMID: 37191946 PMC: 10292934. DOI: 10.1096/fj.202202111RR.