Introduction
breast milk
CYSTIC FIBROSIS, CHOLINE DEFICIENCY
Nutritional supply of choline as an essential nutrient is often not sufficient [In preterm infants, plasma levels of choline rapidly fall by 50% after birth, leading to an unphysiological decrease during a time of exponential growth and choline requirements [The liver’s choline homeostasis is important to secrete bile PC for triglyceride emulsification and to synthesise lipoprotein PC for the assembly and secretion of very low-density lipoproteins (VLDL). Notably, choline can be mobilised from the lung as high-density lipoprotein PC, which may become ‘choline-exhausted’ as it comprises only ¼ of the hepatic choline pool, to compensate for the liver’s choline deficiency [Choline requirement is not covered by endogenous synthesis. Choline was, therefore, defined as an essential nutrient by the US-Food and Drug Administration (FDA) and National Academy of Medicine of the USA (NAM) in 1998 and European Food Safety Authority (EFSA) by 2016. NAM defined the adequate intake (AI) for male adults as 550 mg/d (= ~ 7–8 mg/kg/d) [In contrast to choline salts (like choline chloride) as common components in choline supplements, nutritional choline is physiologically provided as organic esters, with phosphorylcholine and GPC dominating in breast milk and PC dominating in regular food after weaning. We aimed to analyse differences in the metabolism and kinetics of these different choline supplements to define their differences in assimilation and effects on plasma concentration of choline and its metabolites and on TMAO formation. Aim was finding an effective and safe supplement resulting in low levels of TMAO in plasma after administration. This will be important for patient groups with typically low levels of choline like preterm infants or patients with cystic fibrosis. Beyond this, we found that PC as a choline supplement, other than water-soluble compounds, substantially affected the metabolism of polyunsaturated fatty acids (LC-PUFA), therefore possibly being a tool in concert with LC-PUFA supplementation. We used D9-choline chloride, D9-phosphorylcholine, D9-GPC and D9-POPC as stable-isotope-labelled analogues of the respective natural choline supplements.