Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial

Authors

Premranjan Kumar
Chun Liu
James Suliburk
Jean W Hsu
Raja Muthupillai
Farook Jahoor
Charles G Minard
George E Taffet
Rajagopal V Sekhar

Publication Date

1-26-2023

Journal

The Journals of Gerontology: Series A

DOI

10.1093/gerona/glac135

PMID

35975308

PMCID

PMC9879756

PubMedCentral® Posted Date

8-17-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Mice, Animals, Aged, Acetylcysteine, Glycine, Health Promotion, Oxidative Stress, Aging, Glutathione, Dietary Supplements, Insulin Resistance, Inflammation, Mitochondria, Clinical trials, GlyNAC, Metabolism, Oxidative stress, Successful aging

Abstract

BACKGROUND: Elevated oxidative stress (OxS), mitochondrial dysfunction, and hallmarks of aging are identified as key contributors to aging, but improving/reversing these defects in older adults (OA) is challenging. In prior studies, we identified that deficiency of the intracellular antioxidant glutathione (GSH) could play a role and reported that supplementing GlyNAC (combination of glycine and N-acetylcysteine [NAC]) in aged mice improved GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR). To test whether GlyNAC supplementation in OA could improve GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks, we conducted a placebo-controlled randomized clinical trial.

METHODS: Twenty-four OA and 12 young adults (YA) were studied. OA was randomized to receive either GlyNAC (N = 12) or isonitrogenous alanine placebo (N = 12) for 16-weeks; YA (N = 12) received GlyNAC for 2-weeks. Participants were studied before, after 2-weeks, and after 16-weeks of supplementation to assess GSH concentrations, OxS, MFO, molecular regulators of energy metabolism, inflammation, endothelial function, IR, aging hallmarks, gait speed, muscle strength, 6-minute walk test, body composition, and blood pressure.

RESULTS: Compared to YA, OA had GSH deficiency, OxS, mitochondrial dysfunction (with defective molecular regulation), inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC (and not placebo) supplementation in OA improved/corrected these defects.

CONCLUSION: GlyNAC supplementation in OA for 16-weeks was safe and well-tolerated. By combining the benefits of glycine, NAC and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities to promote health in aging humans.

Comments

Clinical Trials Registration Number: NCT01870193

Associated Data