ArticleClinical and translational medicine2021
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.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- The impact of cysteine on lifespan in three model organisms: A systematic review and meta-analysis.Aging cell · 2025Pooled it
- Pooled it
- Metabolomic profiles impacted by brief mindfulness intervention with contributions to improved health.Scientific reports · 2025Trial
- 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.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Trial
- Trial
- Oxidative stress in neurodegeneration: from a simple insult to a dynamic regulator.Redox report : communications in free radical research · 2026Review
- Amino acid infusion and acute kidney injury after aortic surgery: a multicenter observational study with target trial emulation.Renal failure · 2026Observational
- Prodh2-Mediated Mitochondrial Stress Drives TNF-α-Induced Myoblast Dysfunction and Sarcopenia in COPD.Aging cell · 2026Article
- Hippocampal snRNA-seq in Collaborative Cross reveals molecular signatures of cognitive resilience independent of chronological aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Review
- Ferroptosis-related stress during aging and its relevance to disease.GeroScience · 2026Review
- eNOS Uncoupling, Shear-Stress Tolerance, and the Two-Threshold Model of Post-Exertional Malaise in Long COVID: A Mechanistic Hypothesis With Implications for Physiotherapy and Recovery Protocols.Microcirculation (New York, N.Y. : 1994) · 2026Review
- Circulating PBX1 and age-related sarcopenia phenotypes: metabolic mediation analyses in a community-based study.European geriatric medicine · 2026Article
- Bioactive Collagen Peptides in Veterinary and Biomedical Science-Part II: The Gut-Collagen Peptide Axis, Bile Acid Signaling, and Translational Therapeutic Applications.Veterinary sciences · 2026Review
- Bioactive Collagen Peptides in Veterinary and Biomedical Science-Part I: Molecular Identity, Gastrointestinal Bioavailability, and Receptor-Mediated Signaling, with Relevance to the Bile Acid Axis.Veterinary sciences · 2026Review
- Efficacy and Safety of Glutathione Supplementation in Type 2 Diabetes & Diabetes Complications.Nutrients · 2026Review
- Association between the cumulative average triglyceride glucose-BMI and hypertension incidence among the middle-aged and older population: a prospective nationwide cohort study in China.Journal of hypertension · 2026Article
- Expression Analysis of Mitochondrial Energy Metabolism-Related Genes Identifies IRS2 as a Key Modulator in M2 Synovial Macrophages of Osteoarthritis.Biomedicines · 2026Article
- Phytochemical-Based Therapeutic Strategies for Sarcopenia: From Molecular Mechanisms to Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeted Supplementation and Nutritional Strategies for Healthy Aging: A Review of Physiological and Molecular Benefits.Current nutrition reports · 2026Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOxidative 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.
methodsA 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.
resultsGlyNAC 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.
conclusionsGlyNAC 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.