lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Potential Clinical Impact of Choline Supplementation in Cystic Fibrosis Patients

99 Pages Posted: 11 Sep 2018

See all articles by Wolfgang Bernhard

Wolfgang Bernhard

University of Tuebingen - Department of Neonatology

Robert Lange

University of Tuebingen - Department of Neonatology

Ute Graepler-Mainka

University of Tuebingen - Department of Hematology and Oncology

Corinna Engel

University of Tuebingen - Center for Pediatric Clinical Studies

Jürgen Machann

University of Tuebingen - Department of Diagnostic and Interventional Radiology

Verena Hund

University of Tuebingen - Faculty of Medicine

Anna Shunova

University of Tuebingen - Department of Neonatology

Andreas Hector

University of Tuebingen - Department of Hematology and Oncology

Joachim Riethmüller

University of Tuebingen - Department of Hematology and Oncology

More...

Abstract

Rationale: In cystic fibrosis (CF) exocrine pancreas insufficiency results in impaired cleavage of bile phosphatidylcholine and faecal choline loss. Choline is essential for phosphatidylcholine synthesis, and in choline deficiency the liver accretes choline/phosphatidylcholine at the expense of the lungs. Hence, plasma choline and phosphatidylcholine concentrations correlate with lung function.  

Objective: We investigated the effect of choline supplementation on hepatic PC secretion (primary outcome), lung function, liver fat and choline metabolism.  Methods: 10 adult male CF patients were recruited from 11/2014-1/2016 for oral supplementation with 3x1g choline chloride for 84(84-91)d. Pre/post supplementation, patients were spiked with 3.6mg/kg [methyl-D9]choline to assess choline/PC metabolism. Mass spectrometry, spirometry and hepatic nuclear resonance spectrometry served for analysis.  

Main Results: Supplementation decreased plasma D9-PC from 17.7(15.5- 22.4)µmol/L to 12.2(10.5-18.3)µmol/L (t=33h, p<0.01), indicating D9- tracer dilution by higher choline metabolite pools. Whereas plasma PC was unchanged, choline increased from 4.8(4.1-6.2)µmol/L to 14.7(11.8- 16.2)µmol/L at d49, and was 10.5(8.5-15.5)µmol/L at d84 (p<0.01). Supplementation increased forced expiratory volume of 1s percent of predicted (ppFEV1) from 70.0(50.9-74.8)% to 78.3(60.1-83.9)% (p<0.05), and decreased hepatosteatosis from 1.58(0.37-8.82)% to 0.84(0.56-1.17)% liver fat (p<0.01). Post-interventionally, plasma choline returned to baseline concentrations within 60h.

Conclusions: Choline supplementation normalized plasma choline concentration, and increased choline-containing PC precursor pools in adult CF patients. Improved lung function, and resolution of hepatosteatosis, suggest that correcting choline deficiency is clinically important in a systemic approach. Choline supplementation may be a therapeutic perspective for CF patients that should be addressed in prospective, randomized and placebo-controlled trials.  

Clinical Trial Number: Clinical trial registered with clinicaltrials.gov (NCT 03312140).

Funding Statement: Margerete-Müller-Bull-Stiftung, Stuttgart, Germany, for project granting.

Declaration of Interests: The authors have no conflicts of interest to disclose.

Ethics Approval Statement: The protocol was approved by The Institutional Review Board, and registered at ClinicalTrials.gov (Identifier: NCT 03312140). Data collection and management was performed by the Centre for Paediatric Clinical Studies (CPCS) III&IV, University Children’s Hospital, University of Tübingen.

Keywords: cystic fibrosis; choline deficiency; choline supplementation; lung function; magnetic resonance spectroscopy; steatosis; stable isotope labelling

Suggested Citation

Bernhard, Wolfgang and Lange, Robert and Graepler-Mainka, Ute and Engel, Corinna and Machann, Jürgen and Hund, Verena and Shunova, Anna and Hector, Andreas and Riethmüller, Joachim, Potential Clinical Impact of Choline Supplementation in Cystic Fibrosis Patients (July 20, 2018). Available at SSRN: https://ssrn.com/abstract=3218734

Wolfgang Bernhard (Contact Author)

University of Tuebingen - Department of Neonatology ( email )

Calwer Straße 7
Tübingen, D-72076
Germany

Robert Lange

University of Tuebingen - Department of Neonatology

Calwer Straße 7
Tübingen, D-72076
Germany

Ute Graepler-Mainka

University of Tuebingen - Department of Hematology and Oncology

Tübingen
Germany

Corinna Engel

University of Tuebingen - Center for Pediatric Clinical Studies

Tübingen
Germany

Jürgen Machann

University of Tuebingen - Department of Diagnostic and Interventional Radiology

Tübingen
Germany

Verena Hund

University of Tuebingen - Faculty of Medicine

Germany

Anna Shunova

University of Tuebingen - Department of Neonatology

Calwer Straße 7
Tübingen, D-72076
Germany

Andreas Hector

University of Tuebingen - Department of Hematology and Oncology

Tübingen
Germany

Joachim Riethmüller

University of Tuebingen - Department of Hematology and Oncology

Tübingen
Germany

Click here to go to TheLancet.com

Paper statistics

Abstract Views
87
Downloads
8