Reproductive state and choline intake influence enrichment of plasma lysophosphatidylcholine-DHA: a post hoc analysis of a controlled feeding trial

Abstract

The major facilitator superfamily domain 2a protein was identified recently as a lysophosphatidylcholine (LPC) symporter with high affinity for LPC species enriched with DHA (LPC-DHA). To test the hypothesis that reproductive state and choline intake influence plasma LPC-DHA, we performed a post hoc analysis of samples available through 10 weeks of a previously conducted feeding study, which provided two doses of choline (480 and 930 mg/d) to non-pregnant (n 21), third-trimester pregnant (n 26), and lactating (n 24) women; all participants consumed 200 mg of supplemental DHA and 22 % of their daily choline intake as 2H-labelled choline. The effects of reproductive state and choline intake on total LPC-DHA (expressed as a percentage of LPC) and plasma enrichments of labelled LPC and LPC-DHA were assessed using mixed and generalised linear models. Reproductive state interacted with time (P = 0·001) to influence total LPC-DHA, which significantly increased by week 10 in non-pregnant women, but not in pregnant or lactating women. Contrary to total LPC-DHA, patterns of labelled LPC-DHA enrichments were discordant between pregnant and lactating women (P < 0·05), suggestive of unique, reproductive state-specific mechanisms that result in reduced production and/or enhanced clearance of LPC-DHA during pregnancy and lactation. Regardless of the reproductive state, women consuming 930 v. 480 mg choline per d exhibited no change in total LPC-DHA but higher d3-LPC-DHA (P = 0·02), indicating that higher choline intakes favour the production of LPC-DHA from the phosphatidylethanolamine N-methyltransferase pathway of phosphatidylcholine biosynthesis. Our results warrant further investigation into the effect of reproductive state and dietary choline on LPC-DHA dynamics and its contribution to DHA status.

Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial

“…Administration of d9 ‐choline allows tracing of its methyl groups (generated d3 ‐ and d6 ‐deuterium labeled choline metabolites) and the intact choline molecule (generated d9 ‐deuterium labeled choline metabolites) as diagramed previously 3,25,26 . The enrichment percentage of isotopically labeled choline metabolites was calculated as follows:…”

The distribution of dietary choline intake and serum choline levels in Australian women during pregnancy and associated early life factors

“…Greater daily choline intake was associated with increased blood concentrations of choline and betaine, increasing the methyl donor pool for DNA methylation that is essential to foetal development [ 45 ]. Choline supplementation also has an effect on other essential nutrients such as vitamin B-12 [ 47 ] and lysophosphatidylcholine enriched with DHA [ 48 ] status during pregnancy, supporting a functional relationship between these nutrients. Further clinical trial with higher dose intervention (930 mg/day vs 480 mg/day during third trimester) during pregnancy showed improved child memory at year seven [ 49 ].…”

Prenatal choline supplementation improves biomarkers of maternal docosahexaenoic acid (DHA) status among pregnant participants consuming supplemental DHA: a randomized controlled trial

“…As a major consumer of SAM, it is unsurprising that, during the timing of this large increase in estrogen and PEMT activity, plasma biomarkers of choline-derived methyl donors are reduced in human pregnancy ( 10 ), despite “adequate” choline intakes. A higher choline intake (930 vs. 480 mg/d), administered during the third trimester of pregnancy, has been shown to 1 ) attenuate this decline ( 10 ), 2 ) restore choline partitioning between betaine and cytidine diphosphate (CDP)-PC pathways to concentrations observed in nonpregnant women ( 5 ), and 3 ) enhance the generation of PEMT-derived lysophosphatidylcholine (LPC) that is enriched with DHA ( 11 ), and preferentially taken up by fetal brain ( 12 , 13 ). Nonetheless, this higher level of choline intake among third-trimester pregnant women failed to increase PC-DHA ( 7 ) in circulating erythrocytes, possibly because PEMT is already operating at maximal capacity in the last third of gestation.…”