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N-Acetyl-Cysteine and Glycine Co-Supplementation Supports Mitochondrial, Metabolic and Physical Function in Older Adults

Emerging evidence points to one of the body’s chief antioxidants—glutathione— as a modifiable target for supporting mitochondrial function, reducing oxidative stress and maintaining physical function in older adults.

Glutathione (GSH) is an abundant and essential antioxidant in nearly every cell of the body. It directly scavenges reactive oxygen species (ROS), which are byproducts of metabolism that can cause damage to cellular components. Glutathione also mitigates oxidative stress indirectly by regenerating vitamins C and E, and by supporting antioxidant and detoxification enzymes that metabolize reactive substances.

A growing understanding of the medical and nutritional significance of glutathione goes beyond its basic antioxidant functions. Evolving evidence underscores the role of glutathione in maintaining the function of mitochondria—critical energy-producing organelles that power the muscles, brain cells and other tissues. The abundance and efficiency of our mitochondria declines as we grow older (Son and Lee, 2019; Sekhar 2011).

It’s widely accepted that both oxidative stress and mitochondrial dysfunction are key contributors to aging, but vagaries remain regarding clinical translation of this knowledge. There remains an ongoing need for evidence-based dietary supplements for healthy adults hoping to maintain their wellness, strength and physical function into their later years.

It turns out that glutathione connects multiple dots in the antioxidant-mitochondrial constellation of aging and offers insights into nutritional measures to support healthy aging at its cellular roots.

Glutathione happens to be a highly modifiable, measurable and clinically informative marker. It’s also responsive to widely available nutritional factors that help the body make it more efficiently.


Older adults exhibit marked reductions in circulating glutathione compared to younger controls, owing to a decline in their ability to synthesize it from dietary precursors.

The body’s way of making glutathione isn’t very complicated. Cells take 3 amino acids—glycine, cysteine, and glutamic acid—and join them together with the help of certain enzymes. We obtain all three amino acids from the proteins in the foods we eat.

But the mix that reaches cells isn’t always optimal. Cysteine is often in short supply, making it “rate-limiting” or weakest step in the process.  This is why restoring intracellular cysteine levels with N-acetyl-cysteine (NAC) can significantly increase glutathione levels in the body (Pendyala et al, 1995; Tenório et al, 2021).

Compared to younger counterparts, glycine levels are also low in the red blood cells of older adults, suggesting the potential value of NAC-glycine combinations. NAC alone, or in combination with glycine, has been found to support glutathione levels and favorable immunological, respiratory and metabolic outcomes in clinical studies (Herzenberg et al., 1997; De Rosa et al., 2000; Nguyen et al., 2014; Gupta et al., 2016; Kumar et al., 2020; Zheng et al., 2014; Sekhar et al., 2011; Nguyen et al., 2013; Kumar et al., 2021a).


GlyNAC, a 1:1 combination of glycine and NAC, significantly increases intracellular (RBC) glutathione levels in preclinical and clinical studies.  In a small study of older individuals, two weeks of GlyNAC supplementation raised RBC glutathione levels more effectively than NAC or glycine alone (Guthikonda, et al. 2006).

GlyNAC also reduces markers of oxidative stress and promotes mitochondrial function (Kumar et al., 2021, Nguyen et al., 2013; Sekhar et al., 2011), particularly amongst older adults with high glutathione demand (Lizzo et al., 2022).

In a newly published double-blind placebo-controlled trial in the Journal of Gerontology Medical Sciences, 24 healthy older adults (aged 61-80 years) were randomized to receive a high dose of GlyNAC (100 mg/kg/day of glycine and NAC; about 14 g total/day) or placebo. After 16 weeks, GlyNAC increased circulating glutathione levels more than 2-fold (Figure 1) and increased intramuscular glutathione to levels comparable to younger adults.  Significant improvements in oxidative stress were detectable in as early as 2 weeks and reached levels comparable to younger adults by 16 weeks. GlyNAC supplementation also significantly enhanced mitochondrial function and markers of physical function, including grip strength and exercise capacity (Figure 1).

Bar chart depicting positive impacts of GlyNAC supplementation

Figure 1. GlyNAC supplementation increased muscle and red blood cell (RBC) glutathione levels, reduced oxidative stress (TBARS) and enhanced parameters of muscle function, including grip strength and exercise capacity (6-minute walk test).

Pure Encapsulations® NAC + Glycine Powder provides this 1:1 combination of NAC and glycine (3.6 g) to restore and promote glutathione synthesis and antioxidant support for healthy aging.‡

Learn more about the science behind this product.


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