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European Journal of Nutrition
Published in: European Journal of Nutrition 2/2020

01-03-2020 | Nutrition | Original Contribution

Combined choline and DHA supplementation: a randomized controlled trial

Authors: Wolfgang Bernhard, Katrin Böckmann, Christoph Maas, Michaela Mathes, Julia Hövelmann, Anna Shunova, Verena Hund, Erwin Schleicher, Christian F. Poets, Axel R. Franz

Published in: European Journal of Nutrition | Issue 2/2020

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Abstract

Objective

Choline and docosahexaenoic acid (DHA) are essential nutrients for preterm infant development. They are metabolically linked via phosphatidylcholine (PC), a constitutive plasma membrane lipid and the major transport form of DHA in plasma. Plasma choline and DHA-PC concentrations rapidly decline after preterm birth. To improve preterm infant nutrition, we evaluated combined compared to exclusive choline and DHA supplementation, and standard feeding.

Design

Randomized partially blinded single-center trial.

Setting

Neonatal tertiary referral center in Tübingen, Germany.

Patients

24 inborn preterm infants < 32 week postmenstrual age.

Interventions

Standard nutrition (control) or, additionally, enteral choline (30 mg/kg/day), DHA (60 mg/kg/day), or both for 10 days. Single enteral administration of 3.6 mg/kg [methyl-D9-] choline chloride as a tracer at 7.5 days.

Main outcome measures

Primary outcome variable was plasma choline following 7 days of supplementation. Deuterated and unlabeled choline metabolites, DHA-PC, and other PC species were secondary outcome variables.

Results

Choline supplementation increased plasma choline to near-fetal concentrations [35.4 (32.8–41.7) µmol/L vs. 17.8 (16.1–22.4) µmol/L, p < 0.01] and decreased D9-choline enrichment of PC. Single DHA treatment decreased DHA in PC relative to total lipid [66 (60–68)% vs. 78 (74–80)%; p < 0.01], which was prevented by choline. DHA alone increased DHA-PC only by 35 (26–45)%, but combined treatment by 63 (49–74)% (p < 0.001). D9-choline enrichment showed preferential synthesis of PC containing linoleic acid. PC synthesis via phosphatidylethanolamine methylation resulted in preferential synthesis of DHA-containing D3-PC, which was increased by choline supplementation.

Conclusions

30 mg/kg/day additional choline supplementation increases plasma choline to near-fetal concentrations, dilutes the D9-choline tracer via increased precursor concentrations and improves DHA homeostasis in preterm infants.

Trial registration

clinicaltrials.gov. Identifier: NCT02509728.
Appendix
Available only for authorised users
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Metadata
Title
Combined choline and DHA supplementation: a randomized controlled trial
Authors
Wolfgang Bernhard
Katrin Böckmann
Christoph Maas
Michaela Mathes
Julia Hövelmann
Anna Shunova
Verena Hund
Erwin Schleicher
Christian F. Poets
Axel R. Franz
Publication date
01-03-2020
Publisher
Springer Berlin Heidelberg
Keyword
Nutrition
Published in
European Journal of Nutrition / Issue 2/2020
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-019-01940-7

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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