Glutathione is one of the main endogenous antioxidants, acting in the body to recycle other antioxidants and protect the body from free radicals, as well as support detoxification. It is found in virtually every cell of the body and plays a critical role in cell function. Increased glutathione levels have been linked to supporting a reduction in oxidative stress and DNA damage. Cysteine and glycine are necessary precursors for glutathione (GSH) synthesis, and co-supplementation of these nutrients promotes intracellular glutathione levels. The body requires amounts of cysteine and glycine that may not be met by dietary intake alone, particularly as we age. In a small study involving older individuals, two weeks of supplementation with N-acetyl-cysteine (NAC) and/or glycine indicated that the combination NAC + glycine raised red blood cell (RBC) glutathione levels more effectively than either amino acid alone. In one study, supplementation with the combination of NAC and glycine resulted in 32% higher RBC glycine, 46% higher RBC cysteine and a 53% increase in RBC GSH concentration. There was also a significant improvement in the ratio of reduced (active) GSH to oxidized glutathione (GSSG). Increased GSH was associated with improvement in antioxidant status as measured by F2-isoprostanes, as well as mitochondrial fatty acid oxidation. In another study comparing young and older subjects, elderly subjects had 55% lower RBC glycine, 24% lower RBC cysteine, and 46% lower RBC glutathione at baseline, as well as lower reduced (active) GSH to oxidized glutathione (GSSG) ratios. Supplementation with NAC and glycine in elderly subjects resulted in RBC levels of glycine, cysteine, and glutathione, as well as GSH:GSSG ratio, comparable to young unsupplemented subjects. NAC and glycine have been shown to maintain healthy cytokine release during times of metabolic stress. Research suggests that glycine may moderate TNF-a and promote IL-10 to support cytokine balance, and intake has been associated with cardiometabolic health. Studies indicate that supplementation with NAC supports mood and social functioning. It is believed that cysteine influences the reward-reinforcement pathway by modulating the glutamate system. NAC also promotes immune defense and support respiratory health, acting as a free radical scavenger to support epithelial cell health and healthy cilia activity in the respiratory tract. It has a high affinity for lung tissue, which it supports through mucolytic and antioxidant action. In a randomized, double-blind trial involving mostly older individuals, 600 mg of NAC twice daily showed significant support for respiratory and immune function.