Cystic fibrosis and nutrition: linking phospholipids and essential fatty acids with thiol metabolism

Abstract

Cystic fibrosis (CF) is the most common lethal inherited disorder among Caucasians and results from mutation in the gene encoding the CF transmembrane conductance regulator. In addition to its multisystem clinical effects, the disease is characterized by increased proinflammatory mediators and oxidant stress, and systemic redox imbalance with reduced glutathione (GSH), together with alterations in circulating and tissue (n-6) and (n-3) fatty acids, particularly a decrease in docosahexaenoic acid. The metabolism of phospholipids and fatty acids is closely related to GSH through the methionine-homocysteine cycle, in which choline via betaine provides methyl groups to regenerate S-adenosylmethionine, important in generating phosphatidylcholine and amino acid precursors for GSH. Current research focuses both on fatty acid supplementations to normalize altered (n-6) to (n-3) fatty acid balance and decrease generation of (n-6) fatty acid-derived inflammatory mediators, and strategies to improve oxidant defenses and redox balance. However, further research is needed before such strategies can be included in clinical care of individuals with CF.