Evolving nutrition therapy in cystic fibrosis: Adapting to the CFTR modulator era

Abstract

Cystic fibrosis transmembrane regulator (CFTR)-directed therapies, such as modulators, have transformed the medical management of people with CF, resulting in better lung function, weight, and body mass index in recent years. With improved nutrition status in people on CFTR modulators, the emphasis on a high-energy, high-fat diet (the legacy CF diet) is declining, with an increased focus on a healthy diet. The increased survival and median predicted age of people with CF have created a need for more attention to metabolic diseases, including hypertension, dyslipidemia, and cardiovascular diseases. The effects of modulators on extrapulmonary manifestations associated with CF, such as CF-related diabetes, CF hepatobiliary involvement, gastrointestinal tract disorders, and pancreatic manifestations, are currently unknown. Approximately 95% of people with CF qualify for treatment with a CFTR modulator. This review discusses the basics of CFTR gene mutations and changes in nutrition status related to treatment with CFTR modulators.

Keywords: CFTR gene mutations; CFTR modulators; CF‐related diabetes; CF‐related liver disease; aging; cardiometabolic risk; cystic fibrosis (CF); elexacaftor/tezacaftor/ivacaftor (ETI); exocrine pancreatic insufficiency; fat‐soluble vitamin; gastrointestinal manifestations; ivacaftor; legacy CF diet; nutritional therapy; obesity; overweight; vanzacaftor.

Figure 1

Illustration of CFTR function. (A) People without CF. (B) CFTR class mutations in people with CF. CF, cystic fibrosis; CFTR, cystic fibrosis transmembrane regulator. Created in BioRender. Used with permission under BioRender's Academic License. © Sankararaman, S. 2025. https://biorender.com/j00t453.

Figure 2

Data from the Cystic Fibrosis Foundation Patient Registry, 2023 Annual Data Report. Used with permission from the Cystic Fibrosis Foundation.

Figure 3

Cystic fibrosis gut manifestations. CFHBI, cystic fibrosis hepatobiliary involvement; CFLD, cystic fibrosis–related liver disease; CFRD, cystic fibrosis–related diabetes; DIOS, distal intestinal obstruction syndrome; EPI, exocrine pancreatic insufficiency; GERD, gastroesophageal reflux disease; SIBO, small intestinal bacterial overgrowth. Created in BioRender. Used with permission under BioRender's Academic License. © Sankararaman, S. 2025. https://biorender.com/8rotgw5.