使用药理动力学模型优化口服3-基酸盐剂量,以改善健康受试者的认知功能和情绪
Kentaro Nishioka1,2,3, Takahiro Ishimoto2, Mariko Sato1
1Research Institute, Suntory Global Innovation Center Ltd., Kyoto, Japan.
Frontiers in nutrition
|January 27, 2025
概括
口服3 - 甲酸 (3-HB) 可能有助于大脑健康. 一次3.5微克的3-HB剂量改善了健康成年人的认知功能和情绪,证明了它对维持大脑健康的潜力.
科学领域:
- 神经科学是一个神经科学.
- 生物化学 生化学
- 人体生理学 人体生理学
背景情况:
- 大脑利用子,主要是3-甲酸 (3-HB),作为替代能源.
- 假设口服3-HB摄入量通过启动代谢来支持大脑健康.
- 之前的研究表明,血Cmax为0.28mM的3-HB足以触发大脑代谢.
研究的目的:
- 为了证明一个优化的单次口服剂量3-HB对认知功能和情绪的有效性.
- 为了建立口服3-HB的药理动力学模型.
- 为了确定达到大脑子代谢的目标Cmax所需的最低口服剂量.
主要方法:
- 一项涉及健康受试者摄入2和4微克3-HB的药理动力学研究,以开发一个隔间模型.
- 一项使用随机,双盲,安慰剂控制的交叉设计的疗效研究.
- 认知和情绪评估包括序列算术测试 (SAT),CogniTrax,情绪状态概况第二版 (POMS2) 和疲劳视觉模拟量表 (VAS).
主要成果:
- 一个单间模型预测了最低口服剂量为3.5μg的3-HB,以达到目标Cmax.
- 与安慰剂相比,在3.5μg 3-HB组的SAT总响应和正确答案中观察到显著的改善.
- 3.5微克的3-HB剂量显著改善了POMS2尺度 (混乱-困惑,疲劳-惯性,活力-活动,总情绪障碍) 并降低了疲劳VAS得分.
结论:
- 成功建立了一种口服3-HB摄入的单间模型.
- 在健康受试者中,单次口服3.5μg的3-HB剂量显示出对认知功能的部分疗效和对情绪的广泛疗效.
- 这些发现支持了优化口服3-HB剂量的潜力,以保持大脑健康.
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