Essential Fatty Acid Deficiency in Cystic Fibrosis Disease Progression: Role of Genotype and Sex

Adequate intake of nutrients such as essential fatty acids (EFA) are critical in cystic fibrosis (CF). The clinical course of deterioration of lung function in people with CF has been shown to relate to nutrition. Independent of the higher energy consumption and malabsorption due to pancreatic insufficiency, EFA deficiency is closely associated with the risk of pulmonary infection, the most significant pathology in CF. This review will focus on the EFA deficiency identified in people with CF, as well as the limited progress made in deciphering the exact metabolic pathways that are dysfunctional in CF. Specifically, people with CF are deficient in linoleic acid, an omega 6 fatty acid, and the ratio of arachidonic acid (omega 6 metabolite) and docosahexaenoic acid (omega 3 metabolite) is increased. Analysis of the molecular pathways in bronchial cells has identified changes in the enzymes that metabolise EFA. However, fatty acid metabolism primarily occurs in the liver, with EFA metabolism in CF liver not yet investigated, indicating that further research is required. Despite limited understanding in this area, it is well known that adequate EFA concentrations are critical to normal membrane structure and function, and thus are important to consider in disease processes. Novel insights into the relationship between CF genotype and EFA phenotype will be discussed, in addition to sex differences in EFA concentrations in people with CF. Collectively, investigating the specific effects of genotype and sex on fatty acid metabolism may provide support for the management of people with CF via personalised genotype- and sex-specific nutritional therapies.

Automated summary

Adequate intake of essential fatty acids (EFA) is critical in cystic fibrosis (CF) patients. EFA deficiency is closely associated with the risk of pulmonary infection, a significant pathology in CF. Although some progress has been made in understanding the dysfunctional metabolic pathways in CF, further research is needed, particularly in investigating EFA metabolism in the liver. Adequate EFA concentrations are important for normal membrane structure and function, and investigating the effects of genotype and sex on fatty acid metabolism may support personalized nutritional therapies for CF management.