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. 2023 Jan 26;78(1):75-89.
From a clinical perspective, GlyNAC could be utilized in a practice setting as a potential solution for a diverse range of age-related health issues. It acts in a myriad of ways, addressing the interplay between oxidative stress, mitochondrial dysfunction, and inflammatory pathways all of which are implicated in aging and a broad range of clinical conditions, including but not limited to cardiovascular disease, neurodegenerative diseases, chronic fatigue and diabetes.
With regard to cardiovascular health, GlyNAC’s antioxidant properties and its role in replenishing intracellular glutathione (GSH) are particularly relevant. Oxidative stress is a key factor in the development and progression of cardiovascular diseases. GlyNAC, by enhancing the cellular antioxidant defense system, holds the potential to mitigate oxidative damage to blood vessels and the heart. Additionally, GlyNAC’s ability to improve endothelial function, as observed in the study, suggests potential benefits in promoting cardiovascular health. This is crucial, as endothelial dysfunction is a common early marker of cardiovascular disease.
Neurodegenerative disorders, characterized by progressive degeneration of the structure and function of the nervous system, may also be influenced by GlyNAC. Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of conditions like Alzheimer’s and Parkinson’s diseases. Given GlyNAC’s capacity to address these factors, it may offer neuroprotective effects. By supporting mitochondrial function and reducing oxidative stress, GlyNAC could potentially contribute to the preservation of neuronal health and function.
Chronic fatigue, a complex and often debilitating condition, is characterized by persistent fatigue that is not alleviated by rest. While the causes of chronic fatigue are multifaceted, mitochondrial dysfunction and oxidative stress have been suggested as contributing factors. GlyNAC’s role in optimizing mitochondrial function and combating oxidative stress positions it as a potential therapeutic avenue for addressing the energy deficits and fatigue associated with this condition.
In the context of diabetes, GlyNAC’s influence on insulin resistance, as highlighted in the study, underscores its relevance in metabolic health. Diabetes is characterized by impaired insulin action, leading to elevated blood glucose levels. GlyNAC’s potential to enhance insulin sensitivity and improve glucose metabolism suggests a role in diabetes management. The mechanisms underlying these effects may involve the modulation of molecular regulators of energy metabolism, optimizing cellular responses to insulin.
Aging is associated with elevated oxidative stress (OxS), mitochondrial dysfunction, and various hallmarks of aging. Addressing these challenges in older adults (OA) has proven difficult. Previous studies have implicated intracellular glutathione (GSH) deficiency as a potential contributor to these issues. The supplementation of GlyNAC, a combination of glycine and N-acetylcysteine (NAC), in aged mice demonstrated improvements in GSH deficiency, OxS, mitochondrial fatty-acid oxidation (MFO), and insulin resistance (IR).
To investigate the impact of GlyNAC supplementation on GSH deficiency, OxS, mitochondrial dysfunction, IR, physical function, and aging hallmarks in older adults, a placebo-controlled randomized clinical trial was conducted.
Twenty-four older adults (OA) and 12 young adults (YA) participated in the study. OA were randomized to receive either GlyNAC (N = 12) or an isonitrogenous alanine placebo (N = 12) for 16 weeks, while YA (N = 12) received GlyNAC for 2 weeks. Assessments were conducted before, after 2 weeks, and after 16 weeks of supplementation, measuring various parameters such as 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.
Compared to young adults, older adults exhibited GSH deficiency, OxS, mitochondrial dysfunction, inflammation, endothelial dysfunction, IR, multiple aging hallmarks, impaired physical function, increased waist circumference, and systolic blood pressure. GlyNAC supplementation in older adults, and not the placebo, demonstrated improvements in these defects.
The 16-week GlyNAC supplementation was found to be safe and well-tolerated in older adults. By leveraging the combined benefits of glycine, NAC, and GSH, GlyNAC emerged as an effective nutritional supplement capable of improving and reversing multiple age-associated abnormalities. The study supports the potential of GlyNAC to promote health in aging humans.