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

Kevin C Klatt, Melissa Q McDougall, Olga V Malysheva, Siraphat Taesuwan, Aura Alex P Loinard-González, Julie E H Nevins, Kara Beckman, Ruchika Bhawal, Elizabeth Anderson, Sheng Zhang, Erica Bender, Kristina H Jackson, D Janette King, Roger A Dyer, Srisatish Devapatla, Ramesh Vidavalur, J Thomas Brenna, Marie A Caudill, Kevin C Klatt, Melissa Q McDougall, Olga V Malysheva, Siraphat Taesuwan, Aura Alex P Loinard-González, Julie E H Nevins, Kara Beckman, Ruchika Bhawal, Elizabeth Anderson, Sheng Zhang, Erica Bender, Kristina H Jackson, D Janette King, Roger A Dyer, Srisatish Devapatla, Ramesh Vidavalur, J Thomas Brenna, Marie A Caudill

Abstract

Background: Dietary methyl donors (e.g., choline) support the activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway, which generates phosphatidylcholine (PC) molecules enriched in DHA that are exported from the liver and made available to extrahepatic tissues.

Objectives: This study investigated the effect of prenatal choline supplementation on biomarkers of DHA status among pregnant participants consuming supplemental DHA.

Methods: Pregnant participants (n = 30) were randomly assigned to receive supplemental choline intakes of 550 mg/d [500 mg/d d0-choline + 50 mg/d deuterium-labeled choline (d9-choline); intervention] or 25 mg/d (25 mg/d d9-choline; control) from gestational week (GW) 12-16 until delivery. All participants received a daily 200-mg DHA supplement and consumed self-selected diets. Fasting blood samples were obtained at baseline, GW 20-24, and GW 28-32; maternal/cord blood was obtained at delivery. Mixed-effects linear models were used to assess the impact of prenatal choline supplementation on maternal and newborn DHA status.

Results: Choline supplementation (550 vs. 25 mg/d) did not achieve a statistically significant intervention × time interaction for RBC PC-DHA (P = 0.11); a significant interaction was observed for plasma PC-DHA and RBC total DHA, with choline supplementation yielding higher levels (+32-38% and +8-11%, respectively) at GW 28-32 (P < 0.05) and delivery (P < 0.005). A main effect of choline supplementation on plasma total DHA was also observed (P = 0.018); its interaction with time was not significant (P = 0.068). Compared with controls, the intervention group exhibited higher (P = 0.007; main effect) plasma enrichment of d3-PC (d3-PC/total PC). Moreover, the ratio of d3-PC to d9-PC was higher (+50-67%; P < 0.001) in the choline intervention arm (vs. control) at GW 20-24, GW 28-32, and delivery.

Conclusions: Prenatal choline supplementation improves hepatic DHA export and biomarkers of DHA status by bolstering methyl group supply for PEMT activity among pregnant participants consuming supplemental DHA. This trial is registered at www.clinicaltrials.gov as NCT03194659.

Keywords: PEMT pathway; docosahexaenoic acid; omega-3 polyunsaturated fatty acids; pregnancy; prenatal choline supplementation; stable isotope.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study. CONSORT, Consolidated Standards of Reporting Trials.
FIGURE 2
FIGURE 2
Effect of prenatal choline supplementation (n = 15 per group) on maternal RBC PC-DHA (A), maternal plasma PC-DHA (B), maternal RBC total DHA (C), and maternal plasma total DHA (D) among pregnant participants consuming 200 mg supplemental DHA/d. The effect of prenatal choline supplementation on maternal RBC and plasma DHA outcomes was assessed using mixed linear models that included choline intervention × time interaction terms as well as baseline values for the respective outcome. Estimated marginal means and 95% CIs derived from the baseline adjusted models are shown. Statistically significant differences (P < 0.05) between the choline intervention and control values at a study time point are indicated by “*” for models with a significant (P < 0.05) choline intervention × time interaction term (i.e., maternal plasma PC-DHA and maternal total RBC DHA) and by “±” at study end for models with a significant main effect of the choline intervention (i.e., maternal plasma total RBC DHA). GW, gestational week; PC, phosphatidylcholine.
FIGURE 3
FIGURE 3
Effect of prenatal choline supplementation (n = 15 per group) on maternal plasma total PC (A), d3-PC (B), d9-PC (C), and d3:d9-PC (D). The effect of prenatal choline supplementation on maternal total and labeled PC was assessed using mixed linear models that included choline intervention × time interaction terms. Estimated marginal means and 95% CIs are shown; total PC concentrations represented models adjusted for visit 1 plasma PC. Statistically significant differences (P < 0.05) between the choline intervention and control values at a study time point are indicated by “*” for models with a significant (P < 0.05) choline intervention × time interaction term (i.e., maternal plasma total PC and d3:d9-PC) and by “±” at study end for models with a significant main effect of the choline intervention (i.e., d3-PC and d9-PC). d3, tri-deuterated; d9, nona-deuterated; GW, gestational week; PC, phosphatidylcholine.

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