Choline Supplementation in Cystic Fibrosis—The Metabolic and Clinical Impact

Abstract

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.

Differential metabolism of choline supplements in adult volunteers

“…Choline is an essential nutrient, and its supply is regarded as critical in parts of the general population and certain medical conditions [1][2][3]. It is required for the formation of phosphatidylcholine (PC) and sphingomyelin (SPH), two phospholipids with tightly regulated concentrations in the cell membranes of all tissues and many secretions (bile, lipoproteins, surfactant).…”

Choline Content of Term and Preterm Infant Formulae Compared to Expressed Breast Milk—How Do We Justify the Discrepancies?

“…Analysis was performed as previously described [ 20 , 22 , 26 ] with minor modifications. The mass spectrometry device imbedded a Finnigan Surveyor Autosampler Plus, a Finnigan Surveyor MS Pump Plus, and a TSQ Quantum Ultra equipped with a heated electrospray ionization interface (H-ESI) (Thermo Fisher Scientific, Dreieich, Germany).…”

“…Individual molecular species were analyzed at positive ionization in the selected reaction monitoring (SRM) mode. Phosphocholine ( m / z = +184) was used as the diagnostic fragment for PC, SPH, and lyso-PC analysis, where individual molecular species were summed up, as previously described [ 20 , 22 ].…”

“…Choline supply is regarded as being critical in preterm infants, i.e., after untimely cessation of trans-placental supply [ 2 , 19 , 20 ]. PC and SPH concentrations are high in parenchymal organs, such as the liver, lungs, and brain, so that choline accretion is high during the third trimester and should be high in preterm infants to enable physiologic parenchymal growth [ 8 , 16 ].…”

“…Comparable components for free choline supplementation are choline salts, such as choline chloride or bitartrate. With the start of breast milk feeding (after both preterm and term delivery), however, choline is mainly provided in the form of glycerophosphocholine (GPC) and phosphocholine, with minor contributions of PC, lyso-PC, SPH, and free choline [ 20 , 29 ]. After weaning, PC is the major organic choline component in fresh meat, fish, eggs, legume seeds, nuts, and cereals [ 30 ].…”