Stubbs Brianna J, Stephens Elizabeth B, Senadheera Chatura, Diaz Stephanie Roa, Peralta Sawyer, Alexander Laura, Silverman-Martin Wendie, Kurtzig Jamie, Fernando B Ashen, Yurkovich James T, Garcia Thelma Y, Yukawa Michi, Morris Jennifer, Johnson James B, Newman John C
Buck Institute for Research on Aging, Novato, CA, USA.
Phenome Health, Seattle, WA, USA.
medRxiv. 2024 Sep 18:2024.09.17.24313811. doi: 10.1101/2024.09.17.24313811.
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 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.
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).
Randomized, placebo-controlled, double-blinded, parallel-group, pilot trial of 12-weeks of daily KE ingestion.
The Clinical Research Unit at the Buck Institute for Research on Aging, California.
Community-dwelling older adults (≥ 65 years), independent in activities of daily living, with no unstable acute medical conditions (n = 30).
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.
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.
There were no statistically significant longitudinal differences between groups in exploratory functional, activity-based or quality of life outcomes.
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.
酮体是在禁食或生酮饮食期间产生的代谢产物，在模型中对导致虚弱的炎症和代谢衰老途径具有多效性作用。酮酯（KEs）是在不改变饮食的情况下诱导高酮血症的化合物，可能会影响年轻人的身体和认知功能。KEs对老年人的功能影响尚未得到研究。
我们的长期目标是研究KEs是否能调节与老年人虚弱相关的衰老生物学机制和临床结局。在此，我们报告了在一项为期12周的KE安全性和耐受性研究（NCT05585762）中收集的探索性功能和生活质量结局指标。
每日摄入KE 12周的随机、安慰剂对照、双盲、平行组试点试验。
加利福尼亚州巴克衰老研究所临床研究室。
社区居住的老年人（≥65岁），日常生活活动独立，无不稳定的急性疾病（n = 30）。
受试者被随机分配（1:1），每天摄入25 g的KE（双辛酰基（R）-1,3-丁二醇）或含有菜籽油的口味、外观和热量匹配的安慰剂（PLA）。
在n = 23名完成者（n = 11名PLA，n = 12名KE）中，评估身体功能、认知功能和生活质量的纵向变化作为探索性结局。计算了一个描述活力-虚弱连续体的综合功能结局。在整个研究过程中使用数字可穿戴设备测量心率和活动。
在探索性功能、基于活动的或生活质量结局方面，两组之间没有统计学上的显著纵向差异。
在这个健康老年人的试点队列中，每日摄入25 g的KE不会影响探索性功能或生活质量终点。未来的工作将在更大规模的虚弱前期老年人试验中把这些终点作为主要和次要结局来研究。
