Daily consumption of ketone ester, bis octanoyl (R)-1,3-butanediol does not impact functional and quality of life outcomes in healthy older adults, a randomized, parallel arm, double-blind, placebo-controlled study

Abstract

Background: Ketone bodies are metabolites produced during fasting or on a ketogenic diet that have pleiotropic effects on inflammatory and metabolic aging pathways that underpin frailty in laboratory animal models. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, that have been suggested to impact physical and cognitive function in young adults. The functional effects of KEs have not been studied in older adults. Objectives: Our long-term goal is to examine if KEs modulate aging biology mechanisms and clinical outcomes relevant to frailty in older adults. Here we report the exploratory functional and quality of life outcome measures collected during a 12-week safety and tolerability study of KE (NCT05585762) Design: Randomized, placebo-controlled, double-blinded, parallel-group, pilot trial of 12-weeks of daily KE ingestion. Setting: The Buck Institute for Research on Aging, Northern California. Participants: Community-dwelling older adults (≥ 65 years), independent in activities of daily living, with no unstable acute medical conditions (n = 30). Intervention: Subjects were randomly allocated (1:1) to consume 25 g of either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil daily. Measurements: Physical function, cognitive function and quality of life were assessed before and after the intervention as exploratory outcomes in n = 23 completers. A composite functional outcome was calculated based on previous reports. Heart rate and activity was measured throughout the study. Results: There were no consistent differences between groups in the change in exploratory functional, activity-based or quality of life outcomes. Conclusion: Daily ingestion of 25 g of KE did not affect our exploratory functional or quality of life end points in this pilot cohort of healthy older adults. Future work will address these endpoints as primary and secondary outcomes in a larger trial of pre-frail older adults.