Exploratory functional and quality of life outcomes with daily consumption of the ketone ester bis-octanoyl (R)-1,3-butanediol 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 the inflammatory and metabolic aging pathways underpinning frailty in vivo models. Ketone esters (KEs) are compounds that induce hyperketonemia without dietary changes and that may 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 Clinical Research Unit at the Buck Institute for Research on Aging, California.

Participants: Community-dwelling older adults (≥65 years), independent in activities of daily living, with no unstable acute medical conditions (n = 30).

Intervention: Participants were randomly allocated (1:1) to consume 25 g daily of either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil.

Measurements: Longitudinal change in physical function, cognitive function and quality of life were assessed as exploratory outcomes in n = 23 completers (n = 11 PLA, n = 12 KE). A composite functional outcome intended for interventional frailty trials was derived and calculated. Heart rate and activity was measured throughout the study using digital wearables.

Results: There were no statistically significant longitudinal differences between groups in exploratory functional, activity-based or quality of life outcomes.

Conclusion: Daily ingestion of 25 g of KE did not affect 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.

Keywords: BO-BD; Beta-hydroxybutyrate; Cognition; Exogenous ketone; Frailty; Geroscience; Ketone di-ester; Ketone ester; Ketones; Physical function; Quality of life; Strength.