Choline-related supplements improve abnormal plasma methionine-homocysteine metabolites and glutathione status in children with cystic fibrosis

Background: Liver triacylglycerol accumulation and oxidative stress are common in cystic fibrosis (CF) and also occur in choline deficiency. Previously, we showed an association between elevated plasma homocysteine, reduced ratios of S-adenosylmethionine to S-adenosylhomocysteine (SAM:SAH) and of phosphatidylcholine to phosphatidylethanolamine, and phospholipid malabsorption in children with CF. Objective: The objective was to address a possible relation between altered methionine-homocysteine metabolism and choline metabolism in children with CF. Design: Children with CF were assigned without bias to supplementation with 2 g lecithin/d (n = 13), 2 g choline/d (n = 12), or 3 g betaine/d (n = 10) for 14 d. Plasma concentrations of methionine, adenosine, cysteine, cysteinyl-glycine, glutathione, glutathione disulfide (GSSG), and fatty acids; SAM:SAH; and red blood cell phospholipids were measured within each group of children with CF before and after supplementation. Plasma from healthy children without CF (n = 15) was analyzed to obtain reference data. Results: Children with CF had higher plasma homocysteine, SAH, and adenosine and lower methionine, SAM:SAH, and glutathione: GSSG than did children without CF. Supplementation with lecithin, choline, or betaine resulted in a significant increase in plasma methionine, SAM, SAM:SAH, and glutathione:GSSG and a decrease in SAH (n = 35). Supplementation with choline or betaine was associated with a significant decrease in plasma SAH and an increase in SAM:SAH, methionine, and glutathione:GSSG. Supplementation with lecithin or choline also increased plasma methionine and SAM. Conclusion: We showed that dietary supplementation with choline-related compounds improves the low SAM:SAH and glutathione redox balance in children with CF.