在老年人中补充甘氨酸和N-乙酰半胱氨酸（GlyNAC）可改善谷胱甘肽缺乏、氧化应激、线粒体功能障碍、炎症、胰岛素抵抗、内皮功能障碍、基因毒性、肌肉力量和认知：一项试点临床试验的结果。

Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial.

作者信息

Kumar Premranjan, Liu Chun, Hsu Jean W, Chacko Shaji, Minard Charles, Jahoor Farook, Sekhar Rajagopal V

机构信息

Translational Metabolism Unit, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas, 77030, USA.

USDA/ARS Children's Nutritional Research Center, Houston, Texas, USA.

出版信息

Clin Transl Med. 2021 Mar;11(3):e372. doi: 10.1002/ctm2.372.

DOI:10.1002/ctm2.372

PMID:33783984

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8002905/

Abstract

BACKGROUND

Oxidative stress (OxS) and mitochondrial dysfunction are implicated as causative factors for aging. Older adults (OAs) have an increased prevalence of elevated OxS, impaired mitochondrial fuel-oxidation (MFO), elevated inflammation, endothelial dysfunction, insulin resistance, cognitive decline, muscle weakness, and sarcopenia, but contributing mechanisms are unknown, and interventions are limited/lacking. We previously reported that inducing deficiency of the antioxidant tripeptide glutathione (GSH) in young mice results in mitochondrial dysfunction, and that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improves naturally-occurring GSH deficiency, mitochondrial impairment, OxS, and insulin resistance. This pilot trial in OA was conducted to test the effect of GlyNAC supplementation and withdrawal on intracellular GSH concentrations, OxS, MFO, inflammation, endothelial function, genotoxicity, muscle and glucose metabolism, body composition, strength, and cognition.

METHODS

A 36-week open-label clinical trial was conducted in eight OAs and eight young adults (YAs). After all the participants underwent an initial (pre-supplementation) study, the YAs were released from the study. OAs were studied again after GlyNAC supplementation for 24 weeks, and GlyNAC withdrawal for 12 weeks. Measurements included red-blood cell (RBC) GSH, MFO; plasma biomarkers of OxS, inflammation, endothelial function, glucose, and insulin; gait-speed, grip-strength, 6-min walk test; cognitive tests; genomic-damage; glucose-production and muscle-protein breakdown rates; and body-composition.

RESULTS

GlyNAC supplementation for 24 weeks in OA corrected RBC-GSH deficiency, OxS, and mitochondrial dysfunction; and improved inflammation, endothelial dysfunction, insulin-resistance, genomic-damage, cognition, strength, gait-speed, and exercise capacity; and lowered body-fat and waist-circumference. However, benefits declined after stopping GlyNAC supplementation for 12 weeks.

CONCLUSIONS

GlyNAC supplementation for 24-weeks in OA was well tolerated and lowered OxS, corrected intracellular GSH deficiency and mitochondrial dysfunction, decreased inflammation, insulin-resistance and endothelial dysfunction, and genomic-damage, and improved strength, gait-speed, cognition, and body composition. Supplementing GlyNAC in aging humans could be a simple and viable method to promote health and warrants additional investigation.

摘要

背景

氧化应激（OxS）和线粒体功能障碍被认为是衰老的致病因素。老年人（OA）中氧化应激升高、线粒体燃料氧化（MFO）受损、炎症加剧、内皮功能障碍、胰岛素抵抗、认知能力下降、肌肉无力和肌肉减少症的患病率增加，但相关机制尚不清楚，且干预措施有限或缺乏。我们之前报道，在年轻小鼠中诱导抗氧化三肽谷胱甘肽（GSH）缺乏会导致线粒体功能障碍，而在老年小鼠中补充甘氨酸-N-乙酰半胱氨酸（GlyNAC，甘氨酸和N-乙酰半胱氨酸[NAC]的组合）可改善自然发生的GSH缺乏、线粒体损伤、氧化应激和胰岛素抵抗。在OA患者中进行的这项试点试验旨在测试补充和停用GlyNAC对细胞内GSH浓度、氧化应激、MFO、炎症、内皮功能、遗传毒性、肌肉和葡萄糖代谢、身体成分、力量和认知的影响。

方法

对8名OA患者和8名年轻人（YA）进行了一项为期36周的开放标签临床试验。所有参与者完成初始（补充前）研究后，YA退出研究。OA患者在补充GlyNAC 24周并停用12周后再次接受研究。测量指标包括红细胞（RBC）GSH、MFO；氧化应激、炎症、内皮功能、葡萄糖和胰岛素的血浆生物标志物；步速、握力、6分钟步行试验；认知测试；基因组损伤；葡萄糖生成和肌肉蛋白分解率；以及身体成分。