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

Abstract

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.

Differences in Plasma Fatty Acid Composition Related to Chronic Pancreatitis

“…However, our data align with previously published studies suggesting there is a dysregulation of linoleic acid metabolism, indicated by increased metabolites in CP, 53 or a reduction in linoleic acid absorption, and an increased de novo lipogenesis in CP and changes of FA composition, including linoleic acid, in diabetes and CP 6,8 . Unexpectedly, we did not observe any differences in FA composition in CP with and without EPD, often seen in patients with cystic fibrosis-associated pancreatitis 54 . Although this study did not have subjects with cystic fibrosis or hyperlipidemia, a future study including these additional forms of pancreatic disease would further determine if our findings can also apply to these subsets of patients.…”

“…6,8 Unexpectedly, we did not observe any differences in FA composition in CP with and without EPD, often seen in patients with cystic fibrosis-associated pancreatitis. 54 Although this study did not have subjects with cystic fibrosis or hyperlipidemia, a future study including these additional forms of pancreatic disease would further determine if our findings can also apply to these subsets of patients.…”

Elevated Prostaglandin E2 Synthesis Is Associated with Clinical and Radiological Disease Severity in Cystic Fibrosis

“…Various CFTR variants related with fatty acid metabolism abnormalities have been reported in CF, such as an abnormally high arachidonic acid (AA) to docosahexaenoic acid (DHA) ratio and a linoleic acid (LA) deficiency, which is directly related to the severity of the CFTR variants [11,[15][16][17].…”

Impact of 1-Year Supplementation with High-Rich Docosahexaenoic Acid (DHA) on Clinical Variables and Inflammatory Biomarkers in Pediatric Cystic Fibrosis: A Randomized Double-Blind Controlled Trial

“…Adequate nutrition, including the intake of essential fatty acids (EFAs), particularly omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs), is essential in patients with cystic fibrosis (CF) because of the high incidence of EFA deficiency and the role played by this deficiency in fat malabsorption and symptoms and the progression of pulmonary disease [1,2]. Although the prognosis of CF has remarkably improved with the introduction of modulators to target the specific mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene [3], there has been limited progress in defining the underlying mechanisms involved in altered EFA metabolic pathways [4,5] and the anti-inflammatory effect of the dietary modulation of EFA deficiency [6,7].…”