Masedunskas Andrius, de Ciutiis Isabella, Hein Leanne K, Ge Anjie, Kong Yvonne X, Qi Miao, Mainali Drishya, Rogerson-Wood Lara, Kroeger Cynthia M, Aguirre Candia Yvonne A, Cagigas Maria L, Wang Tian, Hutchinson David, Sabag Angelo, Passam Freda H, Piccio Laura, Sargeant Timothy J, Fontana Luigi
Charles Perkins Centre, University of Sydney, Sydney, NSW 2006, Australia.
Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia.
Nutrients. 2024 Dec 12;16(24):4297. doi: 10.3390/nu16244297.
Although prolonged fasting has become increasingly popular, the favourable biological adaptations and possible adverse effects in humans have yet to be fully elucidated.
To investigate the effects of a three-day water-only fasting, with or without exercise-induced glycogen depletion, on autophagy activation and the molecular pathways involved in cellular damage accumulation and repair in healthy humans.
A randomised, single-centre, two-period, two-sequence crossover trial. The primary outcome is autophagic activity, assessed as flux in peripheral blood mononuclear cells (PBMCs) measured in the context of whole blood. Secondary outcomes include changes in body composition, heart rate variability, endothelial function, and genomic, epigenomic, metabolomic, proteomic, and metagenomic adaptations to fasting in plasma, platelets, urine, stools, and PBMCs. Detailed profiling of circulating immune cell populations and their functional states will be assessed by flow cytometry.
All clinical investigations will be undertaken at the Charles Perkins Centre Royal Prince Alfred Hospital clinic, University of Sydney, Australia.
Twenty-four individuals aged 18 to 70 years, with a BMI of 20-40 kg/m, free of major health conditions other than obesity.
While autophagic flux induction through fasting has garnered interest, there is a notable lack of human studies on this topic. This trial aims to provide the most detailed and integrated analysis of how three days of prolonged water-only fasting, combined with glycogen-depleting exercise, affects autophagy activation and other crucial metabolic and molecular pathways linked to cellular, metabolic, and immune health. Insights from this study may pave the way for safe and effective strategies to induce autophagy, offering potential preventive interventions for a range of chronic conditions.
尽管长时间禁食越来越普遍，但人类体内有利的生物学适应性和可能的不良影响尚未完全阐明。
研究为期三天的仅饮水禁食（无论有无运动诱导的糖原消耗）对健康人体内自噬激活以及细胞损伤积累和修复所涉及的分子途径的影响。
一项随机、单中心、两阶段、两序列交叉试验。主要结局是自噬活性，通过全血中测量的外周血单核细胞（PBMC）通量进行评估。次要结局包括身体成分、心率变异性、内皮功能的变化，以及血浆、血小板、尿液、粪便和PBMC中对禁食的基因组、表观基因组、代谢组、蛋白质组和宏基因组适应性。将通过流式细胞术评估循环免疫细胞群体及其功能状态的详细概况。
所有临床研究将在澳大利亚悉尼大学皇家阿尔弗雷德王子医院查尔斯·珀金斯中心诊所进行。
24名年龄在18至70岁之间、体重指数为20 - 40 kg/m²、除肥胖外无重大健康问题的个体。
虽然通过禁食诱导自噬通量引起了关注，但关于这一主题的人体研究明显不足。该试验旨在对为期三天的长时间仅饮水禁食与糖原消耗运动相结合如何影响自噬激活以及与细胞、代谢和免疫健康相关的其他关键代谢和分子途径进行最详细和综合的分析。这项研究的见解可能为诱导自噬的安全有效策略铺平道路，为一系列慢性疾病提供潜在的预防性干预措施。
