Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact firstname.lastname@example.org.
Potential Clinical Impact of Choline Supplementation in Cystic Fibrosis Patients
99 Pages Posted: 11 Sep 2018More...
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: Suggested Citation