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Choline supplementation for preterm infants: metabolism of four Deuterium-labeled choline compounds
Katrin A Böckmann1, Wolfgang Bernhard2, Michaela Minarski2
1Department of Neonatology, Faculty of Medicine, Eberhard Karls University, Calwer Straße 7, 72076, Tuebingen, Germany. katrin.boeckmann@med.uni-tuebingen.de.
Insights
Choline supplementation in preterm infants is crucial. Different forms of deuterated choline were compared, with D9-POPC showing a unique metabolic shift towards phosphatidylcholine (PC) and potential for enhanced poly-unsaturated fatty acid (PUFA) delivery.
Area of Science:
- Biochemistry
- Neonatology
- Nutritional Science
Background:
- Choline is essential for preterm infant development, involved in cell membrane formation (phosphatidylcholine - PC), fatty acid transport (PUFA-PC), and methylation (betaine).
- Inadequate choline supply in preterm infants may lead to developmental issues.
- This study investigated the kinetics of various deuterated choline forms in enterally fed preterm infants.
Purpose of the Study:
- To compare the kinetics of deuterated choline (D9-choline), D9-betaine, and D9-phosphatidylcholine (D9-PC) after administration of different D9-choline components.
- To evaluate the metabolic fate of D9-choline chloride, D9-glycerophosphorylcholine (D9-GPC), and D9-1-palmitoyl-2-oleoyl-PC (D9-POPC) in preterm infants.
- To inform optimal choline supplementation strategies for preterm infants.
Main Methods:
- A prospective study involving 32 enterally fed preterm infants (gestational age 28 0/7–32 0/7 weeks).
- Infants received a single enteral dose of a D9-choline equivalent as D9-choline chloride, D9-GPC, or D9-POPC.
- Plasma concentrations of D9-choline, D9-betaine, and D9-PC were analyzed using tandem mass spectrometry at 1, 12, 24, and 60 hours post-administration.
Main Results:
- D9-Choline chloride, D9-GPC, and D9-phosphoryl-choline similarly increased plasma D9-choline and D9-betaine levels.
- D9-POPC administration did not result in detectable plasma D9-choline but led to the highest plasma D9-PC concentrations.
- Fatty-acyl remodeling of D9-POPC was observed, with a predominance of linoleic acid in D9-PC, suggesting preferential incorporation of poly-unsaturated fatty acids (PUFAs).
Conclusions:
- D9-Choline chloride, D9-GPC, and D9-phosphoryl-choline are effective in increasing plasma D9-choline and D9-betaine.
- D9-POPC uniquely shifts choline metabolism towards D9-PC formation and may facilitate PUFA delivery.
- Combined supplementation strategies, potentially including GPC and (PO)PC, could optimize choline and PUFA supply in preterm infants.
Background:
Supply of choline is not guaranteed in current preterm infant nutrition. Choline serves in parenchyma formation by membrane phosphatidylcholine (PC), plasma transport of poly-unsaturated fatty acids (PUFA) via PC, and methylation processes via betaine. PUFA-PC concentrations are high in brain, liver and lung, and deficiency may result in developmental disorders. We compared different deuterated (D9-) choline components for kinetics of D9-choline, D9-betaine and D9-PC.
Methods:
Prospective study (1/2021-12/2021) in 32 enterally fed preterm infants (28 0/7-32 0/7 weeks gestation). Patients were randomized to receive enterally a single dose of 2.7 mg/kg D9-choline-equivalent as D9-choline chloride, D9-phosphoryl-choline, D9-glycerophosphorylcholine (D9-GPC) or D9-1-palmitoyl-2-oleoyl-PC(D9-POPC), followed by blood sampling at 1 + 24 h or 12 + 60 h after administration. Plasma concentrations were analyzed by tandem mass spectrometry. Results are expressed as median (25th/75th percentile).
Results:
At 1 h, plasma D9-choline was 1.8 (0.9/2.2) µmol/L, 1.3 (0.9/1.5) µmol/L and 1.2 (0.7/1.4) µmol/L for D9-choline chloride, D9-GPC and D9-phosphoryl-choline, respectively. D9-POPC did not result in plasma D9-choline. Plasma D9-betaine was maximal at 12 h, with lowest concentrations after D9-POPC. Maximum plasma D9-PC values at 12 h were the highest after D9-POPC (14.4 (9.1/18.9) µmol/L), compared to the other components (D9-choline chloride: 8.1 [5.6/9.9] µmol/L; D9-GPC: 8.4 (6.2/10.3) µmol/L; D9-phosphoryl-choline: 9.8 (8.6/14.5) µmol/L). Predominance of D9-PC comprising linoleic, rather than oleic acid, indicated fatty-acyl remodeling of administered D9-POPC prior to systemic delivery.
Conclusion:
D9-Choline chloride, D9-GPC and D9-phosphoryl-choline equally increased plasma D9-choline and D9-betaine. D9-POPC shifted metabolism from D9-betaine to D9-PC. Combined supplementation of GPC and (PO) PC may be best suited to optimize choline supply in preterm infants. Due to fatty acid remodeling of (PO) PC during its assimilation, PUFA co-supplementation with (PO) PC may increase PUFA-delivery to critical organs. This study was registered (22.01.2020) at the Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020502.
Study Registration:
This study was registered at the Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020502.
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