Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults in a randomized, parallel arm, double-blind, placebo-controlled, pilot study

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 assess the tolerability and safety of KE ingestion in a cohort of older adults.

Design

Randomized, placebo-controlled, double-blinded, parallel-arm trial (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; M = 15, F = 15; age = 76 y, range 65–90 y) were randomized and n = 23 (M = 14, F = 9) completed the protocol.

Intervention

Participants were randomly allocated to consume either KE (25 g bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched placebo (PLA) containing canola oil daily for 12 weeks.

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 and 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 this study of healthy older adults. These results provide an initial foundation for use of KEs in clinical research with older adults.