Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945-1400, USA.
Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945-1400, USA.
J Nutr Health Aging. 2024 Sep;28(9):100329. doi: 10.1016/j.jnha.2024.100329. Epub 2024 Aug 12.
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.
Randomized, placebo-controlled, double-blinded, parallel-arm trial (NCT05585762).
General community, Northern California, USA.
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.
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.
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.
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.
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.
酮体是在禁食或生酮饮食期间产生的内源性代谢物，对衰老途径具有多效性。酮酯（KEs）是一种在不改变饮食的情况下诱导酮症的化合物，但尚未在老年人群中进行研究。本试验的主要目的是评估 KE 在老年人群中的摄入的耐受性和安全性。
随机、安慰剂对照、双盲、平行臂试验（NCT05585762）。
美国北加州的普通社区。
独立进行日常生活活动的社区居住的老年人，无不稳定的急性医疗条件（n = 30；M = 15，F = 15；年龄 = 76 岁，范围 65-90 岁）被随机分配，n = 23（M = 14，F = 9）完成了方案。
参与者每天随机摄入 KE（25 克双辛酰基（R）-1,3-丁二醇）或含有菜籽油的味道、外观和热量匹配的安慰剂（PLA），持续 12 周。
耐受性通过 2 周的每日日志综合评分进行评估，然后通过每两周一次的电话访谈进行评估。安全性通过筛选和第 0、4 和 12 周的生命体征和实验室检查进行评估，并列出不良事件。
在为期两周的报告期内，报告一天以上中度或重度恶心、头痛或头晕的参与者比例没有差异，这是预先指定的主要结果（KE 组 n = 2（14.3% [90%CI = 2.6-38.5]）；PLA 组 n = 1（7.1% [90%CI = 0.4-29.7]）。PLA 组有 4 人退出，KE 组有 2 人退出。在最初的两周内，两组都报告了更多的症状；在 2 至 12 周期间，症状报告的频率较低。两组的安全性实验室或生命体征均无临床相关变化。
在这项对健康老年人的研究中，这种 KE 是安全且耐受良好的。这些结果为在老年人群中进行 KE 的临床研究提供了初步基础。
