Abstract
Objectives
Ketone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this trial was to determine tolerability and safety of KE ingestion in older adults.
Design
Randomized, placebo-controlled, double-blinded, parallel-arm trial, with a 12-week intervention period ( NCT05585762 ).
Setting
General community, Northern California, USA.
Participants
Community-dwelling older adults, independent in activities of daily living, with no unstable acute medical conditions (n=30) were randomized and n=23 (M= 14, F=9) completed the protocol.
Intervention
Participants were randomly allocated to consume either KE (bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil.
Measurements
Tolerability was assessed using a composite score from a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events.
Results
There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n =2 (14.3% [90% CI = 2.6 – 38.5]); PLA n=1 (7.1% [90% CI = 0.4 – 29.7]). Dropouts numbered four in the PLA group and two in the KE group. A greater number of symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2 – 12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group.
Conclusions
This KE was safe and well-tolerated in healthy older adults. These results provide a foundation for use of KEs in aging research.
Highlights
Ketones esters induce ketosis without dietary changes and may target aging biology
Studies of ketone esters were limited in duration and focused on younger adults
We found ketone esters were safe and tolerable for 12 weeks in healthy older adults
Full Text Availability
The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.