289 Effect of choline and related supplements on methionine-homocysteine metabolism and glutathione status in children with Cystic Fibrosis

Abstract

Introduction: Liver triglyceride accumulation is common in Cystic Fibrosis (CF) and is also a characteristic feature of choline deficiency due to lack of choline for phosphatidylcholine (PC) synthesis via CDP-choline. An alternative PEMT pathway (phosphoethanolamine methyl transferase) to form PC uses phosphatidylethanolamine and methyl groups from methionine via S-adenosylmethionine (SAM) with generation of S-adenosylhomocysteine (SAH). We have also previously shown increased fecal PC excretion, increased plasma homocysteine (HC) and SAH, and decreased SAM/SAH in CF children [1]. Aim: The aim of this study was to assess effects on plasma thiols of choline or choline related dietary supplementation. Subjects and Methods: Pediatric CF patients were given either 14 days lecithin (2g/d, n 13), choline (2 g/d, n 10) or betaine (3 g/d, n 10). Plasma thiols and phospholipids were determined before and after supplementation, and in non-CF children receiving no supplement (n 15). Results: CF children had significantly higher plasma HC and SAH; and lower methionine, SAM/SAH and glutathione GSH/GSSG ratios than children without CF (p < 0.05). Plasma methionine, SAM/SAH and GSSH/GSSG ratios were significantly increased by supplementation with lecithin, choline, or betaine (n 35). All supplements increased SAM/SAH, and supplementation with choline increased GSH/GSSG ratio. Conclusions: These results suggest that supplementation aimed at increasing choline improves altered thiol metabolism and may reduce oxidant stress in CF children. 7. Metabolic complications of CF