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.

Autor:	Stubbs BJ; Buck Institute for Research on Aging, Novato, CA, USA., Stephens EB; Buck Institute for Research on Aging, Novato, CA, USA., Senadheera C; Buck Institute for Research on Aging, Novato, CA, USA., Diaz SR; Buck Institute for Research on Aging, Novato, CA, USA., Peralta S; Buck Institute for Research on Aging, Novato, CA, USA., Alexander L; Buck Institute for Research on Aging, Novato, CA, USA., Silverman-Martin W; Buck Institute for Research on Aging, Novato, CA, USA., Kurtzig J; Buck Institute for Research on Aging, Novato, CA, USA., Fernando BA; Phenome Health, Seattle, WA, USA., Yurkovich JT; Buck Institute for Research on Aging, Novato, CA, USA.; Phenome Health, Seattle, WA, USA., Garcia TY; Buck Institute for Research on Aging, Novato, CA, USA., Yukawa M; Veteran's Affairs Medical Center, San Francisco, CA, USA., Morris J; Veteran's Affairs Medical Center, San Francisco, CA, USA., Johnson JB; Independent Researcher, Greenbrae, CA, USA., Newman JC; Buck Institute for Research on Aging, Novato, CA, USA.; Division of Geriatrics, University of California, San Francisco, CA, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Sep 18. Date of Electronic Publication: 2024 Sep 18.
DOI:	10.1101/2024.09.17.24313811
Abstrakt:	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 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: Subjects 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 to describe the vigor-frailty continuum was 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. Competing Interests: Author Declarations and Conflict Management: The Buck Institute holds shares in BHB Therapeutics (Ireland) and Selah Therapeutics. B.J.S. has stock in H.V.M.N Inc, and stock options in Selah Therapeutics Ltd, BHB Therapeutics (Ireland) Ltd., and Juvenescence Ltd. J.C.N. has stock options in Selah Therapeutics Ltd and BHB Therapeutics (Ireland) Ltd. J.C.N and B.J.S. are inventors on patents related to the use of ketone bodies that are assigned to The Buck Institute. Individual and institutional conflict management plans were developed and approved by the Buck Institute and submitted to the reviewing IRB. Actions and decisions important to participant safety and study integrity were carried out by ‘honest brokers’ with no potential financial conflict. Participant consent was obtained by licensed registered nurses (L.A and W.S.M) who have no financial conflict. Decisions on participant enrollment, continuation, and were made by independent medical officers (J.M and M.Y) unaffiliated with Buck Institute and with no financial conflict. All other authors have no conflicts to report.
Databáze:	MEDLINE
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