Glutathione (GSH) and its precursors (NAC and glycine) are critical in combating oxidative stress, inflammation, and mitochondrial dysfunction.

NAC and glycine supplementation shows promise in improving metabolic, reproductive, cardiovascular, and aging-related health outcomes.

Combined supplementation (e.g., GlyNAC) often yields synergistic benefits, particularly in aging and chronic disease contexts.

Future research should focus on long-term effects, pediatric populations, and broader clinical applications.

The Role of Glutathione and Its Precursors in Type 2 Diabetes – PMC

• Abstract: Type 2 diabetes (T2D) is a major worldwide health crisis affecting about 6.2% of the world’s population. Alarmingly, about one in five children in the USA have prediabetes. Glutathione (GSH) and its precursors play a promising role in the prevention and management of type T2D. Oxidative stress (OxS) is a probable factor in both T2D initiation and progression. GSH is the major cytosolic water-soluble chemical antioxidant and emerging evidence supports its role in improving T2D outcomes. Dietary supplementation with N-acetyl-cysteine (NAC) and/or glycine (GLY), which are GSH precursors, has also been studied for possible beneficial effects on T2D. This review will focus on the underlying pathophysiological and molecular mechanisms linking GSH and its precursors with T2D and OxS. In addition to their traditional antioxidant roles, the in vivo effects of GSH/NAC/GLY supplements will be evaluated for their potential abilities to modulate the complex pro-oxidant pathophysiological factors (e.g., hyperglycemia) driving T2D progression. Positive feedback loops that amplify OxS over long time intervals are likely to result in irreversible T2D micro- and macro-vascular damage. Most clinical studies with GSH/NAC/GLY have focused on adults or the elderly. Future research with pediatric populations should be a high priority since early intervention is critical.

Efficacy of N-acetyl- l-cysteine against glyphosate induced oxidative stress and apoptosis in testicular germ cells preventing infertility – PubMed

• The present era’s demand for continuous pesticides’ use to increase the agriculture outcome, has caused numerous health effects among which mammalian infertility, owing to reproductive toxicity, is serious. Thus, the present study emphasizes upon glyphosate (GLY) induced toxicity and mitigating effects of N-acetyl cysteine (NAC) in testicular cells of caprine by using various cytotoxic and biochemical parameters. GLY was found to induce several apoptotic attributes such as pyknotic nuclei, tubular degeneration, increased vacuolization, and so on, in testicular cells. GLY also decreased the cell viability and increased the incidence of apoptosis in testicular cells in a dose- and time-dependent manner as revealed by MTT assay and Fluorescence (ethidium bromide/acridine orange) assay, respectively. It also increased the level of oxidative stress as evident with an increase in lipid peroxidation and decline in antioxidant power along with the decreased enzymatic activity of different antioxidant enzymes (SOD, CAT, and GST). However, NAC supplementation showed antagonistic results in GLY-treated testicular tissues with maximum amelioration at the highest dose, thereby decreasing GLY-mediated apoptosis rate and oxidative stress. Maximum amelioration was reported at 10 mM NAC concentration. Reduced GLY toxicity due to NAC will prove NAC to be an excellent approach for dealing with male reproductive toxicity at the cellular level, benefiting the mammalian reproductive status.

Improved Cardiovascular Function in Old Mice After N-Acetyl Cysteine and Glycine Supplemented Diet: Inflammation and Mitochondrial Factors – PMC

• The NAC+Gly supplementation improved diastolic function, increasing peak early filling velocity, and reducing relaxation time, left atrial volume, and left ventricle end diastolic pressure. By contrast, cardiac function did not improve with NAC alone. Both diet supplementations decreased cardiac levels of inflammatory mediators; only NAC+Gly reduced leukocyte infiltration. Several mitochondrial genes reduced with aging were upregulated in hearts by NAC+Gly diet supplementation. These Krebs cycle and oxidative phosphorylation enzymes, suggesting improved mitochondrial function, and permeabilized cardiac fibers from NAC+Gly-fed mice produced ATP from carbohydrate and fatty acid sources, whereas fibers from control old mice were less able to utilize fatty acids. Our data indicate that NAC+Gly supplementation can improve diastolic function in the old mouse and may have potential to prevent important morbidities for older people.

Glycine: The Smallest Anti-Inflammatory Micronutrient – PMC

• It this review, we described the importance of glycine as an anti-inflammatory amino acid that not only has beneficial cosmetic effects but is also an alternative medicine for promoting homeostasis in an organism. It has been demonstrated that glycine can modulate the inflammatory response, using different targets in many cells in the entire organism. There are many studies that describe the indirect effects of glycine as a modulator of responses and mechanisms in the organism via dietary supplementation with glycine in animal models and in clinical trials. Another option is including the amino acid as a component of diet using animal models or in clinical trials, finally revealing the indirect role of glycine in reducing the inflammation process and decreasing some symptoms related to low-grade inflammation. However, there are few studies that have evaluated and followed changes due to glycine consumption in the diet over a long period of time, and those that have evaluated how glycine can decrease the risk or development of some diseases related to inflammation process or even the direct effects of glycine on cell activity and the response of cells to specific signals similar to an inflammatory environment.

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 – PMC

• 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 – PMC
• 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.