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随机试验:D-甘油酸激活50至60岁健康人群的线粒体代谢。

Randomized Trial: D-Glyceric Acid Activates Mitochondrial Metabolism in 50-60-Year-Old Healthy Humans.

作者信息

Hirvonen O Petteri, Kyröläinen Heikki, Lehti Maarit, Kainulainen Heikki

机构信息

Faculty of Sport and Health Sciences, Neuromuscular Research Center, University of Jyväskylä, Jyväskylä, Finland.

出版信息

Front Aging. 2021 Oct 29;2:752636. doi: 10.3389/fragi.2021.752636. eCollection 2021.

Abstract

Based on earlier studies, natural metabolite D-glyceric acid (DGA) does not seem to play any role in whole-body metabolism. Nevertheless, one ethanol oxidation-related rat study with controversial results raised our interest. According to preparatory studies for the regulatory approval of DGA, some highly conserved mechanism seems to subtly activate the cellular energy metabolism. Therefore, the present 25-days double-blind human study with placebo control was initiated. The main target in the present study with 27 healthy 50-60-year-old human volunteers was to find out whether an "acute" 4-days and a longer 21-days DGA regimen caused moderate activation of the mitochondrial energy metabolism. The simultaneous target was to find out whether a halved dose of DGA continued to be an effective regimen. The results revealed the following statistically significant findings: 1) plasma concentrations of metabolites related to aerobic energy production, especially lactate, were strongly reduced, 2) systemic inflammation was lowered both in 4- and 21-days, 3) mitochondria-related mRNA expressions in circulating immune cells were noticeably modulated at Day4, 4) cellular membrane integrity seemed to be sharply enhanced, and 5) cellular NADH/NAD -ratio was upregulated. Mitochondrial metabolism was clearly upregulated at the whole-body level in both 4- and 21 days. At the same time, the effect of DGA was very well tolerated. Based on received solid results, the DGA regimen may alleviate acute and chronic energy metabolic challenges in main organs like the liver, CNS, and skeletal muscles. Enhanced membrane integrity combined with lower systemic inflammation and activated metabolic flows by the DGA regimen may be beneficial especially for the aging population.

摘要

基于早期研究,天然代谢产物D-甘油酸(DGA)似乎在全身代谢中不起任何作用。然而,一项关于乙醇氧化的大鼠研究结果存在争议,这引起了我们的兴趣。根据DGA监管批准的前期研究,一些高度保守的机制似乎能微妙地激活细胞能量代谢。因此,开展了这项为期25天、有安慰剂对照的双盲人体研究。本研究以27名年龄在50至60岁之间的健康人类志愿者为主要对象,旨在探究4天的“急性”和更长时间的21天DGA方案是否会引起线粒体能量代谢的适度激活。同时,目标是确定减半剂量的DGA是否仍然是有效的方案。结果显示了以下具有统计学意义的发现:1)与有氧能量产生相关的代谢产物血浆浓度,尤其是乳酸,大幅降低;2)在4天和21天时全身炎症均有所降低;3)循环免疫细胞中线粒体相关的mRNA表达在第4天有明显调节;4)细胞膜完整性似乎大幅增强;5)细胞NADH/NAD比率上调。在4天和21天时,全身水平的线粒体代谢均明显上调。同时,DGA的效果耐受性良好。基于所获得的可靠结果,DGA方案可能缓解肝脏、中枢神经系统和骨骼肌等主要器官的急性和慢性能量代谢挑战。DGA方案增强的膜完整性、较低的全身炎症和激活的代谢流可能对老年人群尤其有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffb0/9261421/6347a3c0c546/fragi-02-752636-g006.jpg

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