Low-dose ketone monoester administration in adults with cystic fibrosis.
Low-Dose Ketone Monoester Administration in Adults with Cystic Fibrosis: A Pilot and Feasibility Study.
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Abstract
INTRODUCTION: Cystic fibrosis transmembrane conductance regulator () modulators have greatly improved outcomes in persons with CF (pwCF); however, there is still significant heterogeneity in clinical responses, particularly with regard to respiratory infection and inflammation. Exogenous administration of ketones has profound systemic anti-inflammatory effects and produces several nutrient-signaling and metabolic effects that may benefit multiple organ systems affected in pwCF. This pilot study was designed to determine the feasibility of administration of a ketone monoester (KME) to increase circulating D-beta hydroxybutyrate concentrations (D-βHB) and to improve subjective measures of CF-specific quality of life and markers of inflammation in serum and sputum in adults with CF. METHODS: Fourteen participants receiving modulator therapy were randomized to receive either KME (n = 9) or placebo control (PC, n = 5) for 5-7 days during hospitalization for treatment of acute pulmonary exacerbation or as outpatients under standard care. RESULTS: The KME was well tolerated, with only mild reports of gastrointestinal distress. D-βHB concentrations increased from 0.2±0.1 mM to 1.6±0.6 mM in the KME group compared to 0.2±0.0 to 0.3±0.1 in the PC group (= 0.011) within 15 min following consumption and remained elevated, relative to baseline, for over 2 h. Pulmonary function was not altered after single- or short-term KME administration, but participants in the KME group self-reported higher subjective respiratory scores compared to PC in both cases (= 0.031). Plasma inflammatory markers were not statistically different between groups following the short-term (5-7 d) intervention (>0.05). However, an exploratory analysis of plasma pre- and post-IL-6 concentrations was significant (= 0.028) in the KME group but not PC. Sputum IFNγ(= 0.057), IL-12p70 (= 0.057), IL-1β(= 0.100), IL-15 (= 0.057), IL-1α(= 0.114), and MPO (= 0.133) were lower in the KME group compared to PC but did not achieve statistical significance. CONCLUSIONS: With the emerging role of exogenous ketones as nutrient signaling molecules and mediators of metabolism, we showed that KME is well tolerated, increases circulating D-βHB concentrations, and produces outcomes that justify the need for large-scale clinical trials to investigate the role of KME on whole-body and tissue lipid accumulation and inflammation in pwCF.
Affiliation
Eric P Plaisance
External References
- PubMed ID:
- 39599743
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