Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria.
Institute of Molecular Biosciences, NAWI Graz, University of Graz, Humboldtstraße 50, Graz 8010, Austria; BioTechMed Graz, Graz 8010, Austria.
Cell Metab. 2019 Sep 3;30(3):462-476.e6. doi: 10.1016/j.cmet.2019.07.016. Epub 2019 Aug 27.
Caloric restriction and intermittent fasting are known to prolong life- and healthspan in model organisms, while their effects on humans are less well studied. In a randomized controlled trial study (ClinicalTrials.gov identifier: NCT02673515), we show that 4 weeks of strict alternate day fasting (ADF) improved markers of general health in healthy, middle-aged humans while causing a 37% calorie reduction on average. No adverse effects occurred even after >6 months. ADF improved cardiovascular markers, reduced fat mass (particularly the trunk fat), improving the fat-to-lean ratio, and increased β-hydroxybutyrate, even on non-fasting days. On fasting days, the pro-aging amino-acid methionine, among others, was periodically depleted, while polyunsaturated fatty acids were elevated. We found reduced levels sICAM-1 (an age-associated inflammatory marker), low-density lipoprotein, and the metabolic regulator triiodothyronine after long-term ADF. These results shed light on the physiological impact of ADF and supports its safety. ADF could eventually become a clinically relevant intervention.
热量限制和间歇性禁食已被证实可延长模式生物的寿命和健康寿命，但其对人类的影响研究较少。在一项随机对照试验研究（ClinicalTrials.gov 标识符：NCT02673515）中，我们表明，严格的隔日禁食（ADF）4 周可改善健康中年人群的一般健康指标，同时平均减少 37%的卡路里。即使超过 6 个月，也没有出现不良反应。ADF 改善了心血管标志物，减少了脂肪量（特别是躯干脂肪），改善了脂肪与瘦肉的比例，并增加了β-羟基丁酸，即使在非禁食日也是如此。在禁食日，包括蛋氨酸在内的促衰老氨基酸会周期性地被消耗，而多不饱和脂肪酸会升高。我们发现长期 ADF 后 sICAM-1（与年龄相关的炎症标志物）、低密度脂蛋白和代谢调节剂三碘甲状腺原氨酸的水平降低。这些结果揭示了 ADF 的生理影响，并支持其安全性。ADF 最终可能成为一种具有临床相关性的干预措施。
