Nutritional Status and Circulating Levels of Fat-Soluble Vitamins in Cystic Fibrosis Patients: A Cohort Study and Evaluation of the Effect of CFTR Modulators

Abstract

Background: Improved therapy in CF has led to an overall improvement in nutritional status. The objectives of our study are: to cross-sectionally assess nutritional status and serum levels of fat-soluble vitamins; to retrospectively evaluate the efficacy of modulators on nutritional status and fat-soluble vitamin levels. Methods: In patients younger than 2 years of age, we evaluated growth, in patients aged 2–18 years, we assessed BMI z-scores, and in adults, we assessed absolute BMI values. Levels of 25(OH)D, vitamins A, and E were measured. Results: A cross-sectional analysis was conducted on 318 patients, 109 (34.3%) with pancreatic sufficiency. Only three patients were under 2 years old. In 135 patients aged 2–18 years, the median BMI z-score was 0.11, and 5 (3.7%) patients had malnutrition (z-score ≤ 2SD). In 180 adults, the median BMI was 21.8 kg/m2. Overall, 15 (13.7%) males (M) and 18 (25.3%) females (F) were underweight (18 < BMI > 20); 3 (2.7%) M and 5 (7.0%) F had a BMI < 18. Suboptimal 25(OH)D levels were found in patients with pancreatic insufficiency. The prevalence of deficiency of vitamins A and E is low. After one year of treatment with modulators, the increase in BMI was more consistent (M: 1.58 ± 1.25 kg/m2 F: 1.77 ± 1.21 kg/m2) in elexacaftor/tezacaftor/ivacaftor (ETI)-treated patients compared with other modulators, with a significant increase in levels of all fat-soluble vitamins. Conclusions: Malnutrition is present in a limited number of subjects. The prevalence of subjects with suboptimal 25(OH)D levels is high. ETI showed a beneficial effect on nutritional status and circulating levels of fat-soluble vitamins.

Nutritional management of people living with cystic fibrosis throughout life and disease continuum: Changing times, new challenges

“…There were no differences in levels of tocopherol and 25hydroxyvitamin D before and after ETI treatment. 41 In other studies examining the impact of ETI treatment on vitamin status, Wright et al 42 observed a modest increase in vitamin D levels in 76 adults after 1 year of treatment whereas Francalanci et al 43 showed significant increases in vitamin A, E and D levels in 29 adults who had been using modulators for at least 1 year. The mechanisms by which ETI affects vitamin levels remain poorly understood but may relate to improved absorption and metabolism of these vitamins combined with a decrease in the adherence to supplementation as patients start to feel better.…”

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

“…It has been suggested that such improvements in the long term might lead to a reduction of osteopenia and fracture risk in adults with CF. Moreover, Fancalanci and collaborators reported in a recent study that ETI therapy not only increased BMI and vitamin D absorption but also vitamins A and E absorption in PwCF, demonstrating the ability of this therapy in improving nutritional status [ 107 ].…”

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

“…Parameters related to nutrient absorption such as weight, BMI, cholesterol and albumin were all significantly increased and the lipid profile improved independent of the diet composition ( Carnovale et al, 2022 ; Petersen et al, 2022 ). Serum levels of fat-soluble vitamins increased ( Wright et al, 2022 ; Francalanci et al, 2023 ) even leading to singular cases of hypervitaminosis ( Miller and Foroozan, 2022 ; Wisnieweski et al, 2022 ). These findings call for adjustments in vitamin supplementation.…”

“…Sweat chloride ppFEV1 Body weight increased (Wright et al, 2022;Francalanci et al, 2023) even leading to singular cases of hypervitaminosis (Miller and Foroozan, 2022;Wisnieweski et al, 2022). These findings call for adjustments in vitamin supplementation.…”