目的:酮体是在禁食或生酮饮食过程中产生的内源性代谢产物,对衰老途径具有多效性作用。酮酯(KE)是在不改变饮食的情况下诱导酮症的化合物,但是KE尚未在老年人群中进行研究。该试验的主要目的是评估老年人群摄入KE的耐受性和安全性。
方法:随机化,安慰剂对照,双盲,平行臂试验(NCT05585762)。
方法:一般社区,北加州,美国。
方法:社区居住的老年人,独立于日常生活活动,没有不稳定的急性医疗条件(n=30;M=15,F=15;年龄=76岁,范围65-90y)随机分配,n=23(M=14,F=9)完成了方案。
方法:参与者被随机分配食用KE(25克二辛酰基(R)-1,3-丁二醇)或口味,外观,和每天含有菜籽油的卡路里匹配安慰剂(PLA),持续12周。
方法:使用2周每日日志的综合评分评估耐受性,然后通过双周电话采访.通过筛选和第0、4和12周时的生命体征和实验室测试以及不良事件的表格来评估安全性。
结果:报告中度或重度恶心的参与者的预设主要结局比例没有差异,头痛,或在两周报告期内超过一天的头晕(KEn=2(14.3%[90%CI=2.6-38.5]);PLAn=1(7.1%[90%CI=0.4-29.7])。解放军组的退学人数为4,KE组的退学人数为2。在前两周,两组均报告了更多的症状;在2到12周之间,症状的报告频率较低。两组的安全性实验室或生命体征均无临床相关变化。
结论:在这项健康老年人的研究中,该KE是安全且耐受性良好的。这些结果为在老年人的临床研究中使用KEs提供了初步基础。
OBJECTIVE: 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.
METHODS: Randomized, placebo-controlled, double-blinded, parallel-arm trial (NCT05585762).
METHODS: General community, Northern California, USA.
METHODS: 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.
METHODS: 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.
METHODS: 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.