Background: Choline is essential for the synthesis of liver phosphatidylcholine (PC), parenchymal maintenance, bile formation, and lipoprotein assembly to secrete triglycerides. In choline deficiency, the liver accretes choline/PC at the expense of lung tissue, thereby impairing pulmonary PC homoeostasis. In cystic fibrosis (CF), exocrine pancreas insufficiency results in impaired cleavage of bile PC and subsequent fecal choline loss. In these patients, the plasma choline concentration is low and correlates with lung function. We therefore investigated the effect of choline supplementation on plasma choline/PC concentration and metabolism, lung function, and liver fat. Methods: 10 adult male CF patients were recruited (11/2014–1/2016), and orally supplemented with 3 × 1 g choline chloride for 84 (84–91) days. Pre-/post-supplementation, patients were spiked with 3.6 mg/kg [methyl-D₉]choline chloride to assess choline/PC metabolism. Mass spectrometry, spirometry, and hepatic nuclear resonance spectrometry served for analysis. Results: Supplementation increased plasma choline from 4.8 (4.1–6.2) µmol/L to 10.5 (8.5–15.5) µmol/L at d84 (p < 0.01). Whereas plasma PC concentration remained unchanged, D₉-labeled PC was decreased (12.2 [10.5–18.3] µmol/L vs. 17.7 [15.5–22.4] µmol/L, p < 0.01), indicating D₉-tracer dilution due to higher choline pools. Supplementation increased Forced Expiratory Volume in 1 second percent of predicted (ppFEV1) from 70.0 (50.9–74.8)% to 78.3 (60.1–83.9)% (p < 0.05), and decreased liver fat from 1.58 (0.37–8.82)% to 0.84 (0.56–1.17)% (p < 0.01). Plasma choline returned to baseline concentration within 60 h. Conclusions: Choline supplementation normalized plasma choline concentration and increased choline-containing PC precursor pools in adult CF patients. Improved lung function and decreased liver fat suggest that in CF correcting choline deficiency is clinically important. Choline supplementation of CF patients should be further investigated in randomized, placebo-controlled trials.

Background: Exocrine pancreatic insufficiency in cystic fibrosis (CF) increases fecal choline losses, but the postnatal course of plasma choline and its metabolites in these patients is unknown. While choline homeostasis is crucial for cellular, bile, and lipoprotein metabolism, via phosphatidylcholine (PC) and via betaine as a methyl donor, choline deficiency is associated with impaired lung and liver function, including hepatic steatosis. Objective: The goal of our study was to evaluate the plasma levels of choline, betaine, trimethylamine oxide (TMAO), PC, and PC subclasses in CF patients from infancy to adulthood and compare those with exocrine pancreatic insufficiency (EPI) to those with pancreatic sufficiency (EPS). Methods: Retrospective analysis of target parameters in plasma samples (July 2015–November 2023) of CF patients (0.64–24.6 years) with tandem mass spectrometry. Results: A total of 477 samples from 162 CF patients were analyzed. In CF patients with EPI (N = 148), plasma choline and betaine concentrations were lower and decreased with age compared to EPS patients showing normal values. TMAO concentrations, indicating intestinal choline degradation by bacterial colonization, were frequently elevated in EPI from infancy onwards, and inversely related to plasma choline and betaine levels. PC-containing linoleic acid levels were lower in EPI, but arachidonic and docosahexaenoic acid content was similar in both patient groups. Conclusion: CF patients with EPI are at risk of choline and betaine deficiency compared to exocrine pancreas-sufficient CF patients. Elevated TMAO concentrations in EPI patients indicate increased bacterial colonization leading to choline degradation before absorption. These findings indicate that laboratory testing of choline, betaine, and TMAO as well as clinical trials on choline supplementation are warranted in CF patients.

Background: Sufficient choline supply is essential for tissue functions via phosphatidylcholine and sphingomyelin within membranes and secretions like bile, lipoproteins and surfactant, and in one-carbon metabolism via betaine. Choline requirements are linked to age and genetics, folate and cobalamin via betaine, and arachidonic (ARA) and docosahexaenoic (DHA) acid transport via the phosphatidylcholine moiety of lipoproteins. Groups at risk of choline deficiency include preterm infants, children with cystic fibrosis (CF) and patients dependent on parenteral nutrition. Fortifiers, formula and supplements may differently impact their choline supply. Objective: To evaluate added amounts of choline, folate, cobalamin, ARA and DHA in fortifiers, supplements and formula used in pediatric care from product files. Methods: Nutrient contents from commonly used products, categorized by age and patient groups, were obtained from public sources. Data are shown as medians and interquartile ranges. Results: 105 nutritional products including fortifiers, formula and products for special indications were analyzed. Choline concentrations were comparable in preterm and term infant formulas (≤6 months) (31.9 [27.6–33.3] vs. 33.3 [30.8–35.2] mg/100 kcal). Products for toddlers, and patients with CF, kidney or Crohn’s disease showed Choline levels from 0 to 39 mg/100 kcal. Several products contain milk components and lecithin-based emulsifiers potentially increasing choline content beyond indicated amounts. Conclusions: Choline addition is standardized in formula for term and preterm infants up to 6 months, but not in other products. Choline content may be higher in several products due to non-declared sources. The potential impact of insufficient choline supply in patients at risk for choline deficiency suggests the need for biochemical analysis of products.

Background: Exocrine pancreatic insufficiency in Cystic Fibrosis (CF) increases fecal choline losses, but the postnatal course of plasma choline and its metabolites in these patients is un-known. While choline homeostasis is crucial for cellular, bile, and lipoprotein metabolism, via phosphatidylcholine (PC) and via betaine as a methyl donor, choline deficiency is associated with impaired lung and liver function, including hepatic steatosis. Objective: To assess plasma levels of choline, betaine, trimethylamine oxide (TMAO), PC, and PC subclasses in CF patients from infancy to adulthood, comparing those with exocrine pancreatic insufficiency (EPI) and sufficiency (EPS). Methods: Retrospective analysis of target parameters in plasma samples (7/2015-11/2023) of CF patients (0.64-24.6 years) with tandem mass spectrometry. Results: A total of 477 samples from 162 CF patients were analyzed. In CF patients with EPI (N=148), plasma choline and betaine concentrations were lower, and decreased with age compared to EPS pa-tients showing normal values. TMAO concentrations, indicating intestinal choline degradation by bacterial colonization, were frequently elevated in EPI from infancy onwards, and inversely related to plasma choline and betaine levels. PC-containing linoleic acid levels were lower in EPI, but arachidonic and docosahexaenoic acid content was similar in both patient groups. Con-clusion: CF patients with EPI are at risk of choline and betaine deficiency compared to exocrine pancreas-sufficient CF patients. Elevated TMAO concentrations in EPI patients indicate in-creased bacterial colonization leading to choline degradation before absorption. These findings indicate that laboratory testing of choline, betaine and TMAO, and clinical trials on choline supplementation are warranted in CF patients.