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

Aging is linked to increased oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, and cognitive decline, all of which contribute to age-related diseases. In the scientific study by Kumar et al., titled 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, researchers investigated whether GlyNAC, a combination of glycine and N-acetylcysteine (NAC), could help counteract these aging-related defects. The study found that supplementing GlyNAC for 24 weeks significantly improved glutathione levels, oxidative stress, mitochondrial function, inflammation, muscle strength, and cognition in older adults. However, after stopping GlyNAC for 12 weeks, these benefits declined, suggesting that continuous supplementation may be necessary to maintain its effects. This research highlights GlyNAC as a potential nutritional strategy to promote healthy aging and reduce the risk of age-related health decline.

Aging leads to several health challenges, including oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, and cognitive decline. These factors contribute to conditions such as muscle weakness, reduced mobility, and an increased risk of chronic diseases like diabetes and neurodegeneration. This scientific study investigates whether supplementing with GlyNAC, a combination of glycine and N-acetylcysteine (NAC), can counteract these issues and promote healthier aging.

The results are promising—after 24 weeks of GlyNAC supplementation, older adults showed significant improvements in muscle strength, cognitive function, insulin resistance, and mitochondrial efficiency. However, when GlyNAC supplementation was stopped, most benefits disappeared, suggesting continuous use may be necessary to maintain the improvements.

Aging is linked to increased oxidative stress, which occurs when harmful molecules known as reactive oxygen species (ROS) build up in the body. Antioxidants normally neutralize these molecules, but our antioxidant defenses weaken as we age, leading to cellular damage. This damage contributes to mitochondrial dysfunction, inflammation, insulin resistance, muscle loss, and cognitive decline.

One of the body’s most important antioxidants is glutathione (GSH), which protects cells from oxidative stress and helps maintain overall cellular health. However, aging is associated with a sharp decline in GSH levels, which leads to increased oxidative damage and impaired mitochondrial function. This study states:

"Aging is associated with a severe glutathione deficiency, which contributes to increased oxidative stress, mitochondrial dysfunction, and metabolic decline."

Since the body requires glycine and cysteine to produce GSH, researchers examined whether supplementing these two nutrients in GlyNAC could help restore GSH levels and improve overall health.

Many studies have focused on NAC alone as a supplement to boost GSH, but research shows that NAC alone is not enough. GSH production also requires glycine; without it, the process remains incomplete. The study explains:

"Glutathione synthesis requires two biochemical steps—first, cysteine combines with glutamic acid to form glutamylcysteine; second, glycine is added to form GSH. Without glycine, GSH synthesis remains incomplete."

By providing both glycine and NAC, GlyNAC ensures the body has all the building blocks necessary to fully restore GSH levels.

This 36-week open-label clinical trial was conducted at Baylor College of Medicine and included eight older adults (aged 71–80) and eight young adults (aged 21–30) as a control group.

The study had three phases. First, researchers measured GSH levels, oxidative stress, mitochondrial function, inflammation, insulin resistance, muscle strength, and cognitive function in all participants. After this baseline measurement, the young adults were released from the study.

Next, the older adults took daily GlyNAC supplements for 24 weeks, and their health markers were re-evaluated at 12 and 24 weeks. Afterward, they stopped taking GlyNAC for 12 weeks to see if the benefits remained. The final measurements were taken at week 36.

To assess GlyNAC's effects, the study measured several health indicators, including oxidative stress markers, mitochondrial function, inflammation levels, insulin resistance, cognitive performance, muscle strength, and genomic damage.

The study revealed that GlyNAC supplementation significantly improved multiple aging-related health issues, but most benefits declined once supplementation stopped.

Before GlyNAC supplementation, older adults had 76% lower GSH levels than younger adults. After 24 weeks, GSH levels increased by 200%, bringing them back to youthful levels. This increase was accompanied by a 75% reduction in oxidative stress markers, suggesting that GlyNAC effectively restored antioxidant defenses and reduced cellular damage.

Older adults initially showed 54% lower mitochondrial efficiency, meaning their cells struggled to produce energy. GlyNAC supplementation corrected these defects, improving mitochondrial function to levels seen in young adults. This improvement is important because mitochondria are the body's powerhouses, responsible for generating the energy needed for muscle movement, brain function, and metabolism.

Inflammation markers such as IL-6, TNF-α, and hsCRP were significantly elevated in older adults before supplementation. After taking GlyNAC for 24 weeks, inflammation levels dropped dramatically. Additionally, fasting insulin levels decreased by 55%, and insulin resistance improved by 59%, suggesting that GlyNAC could help reduce the risk of type 2 diabetes and metabolic disorders.

Older adults who took GlyNAC showed improvements in memory, processing speed, and verbal fluency. Their Montreal Cognitive Assessment (MoCA) scores increased from 26.0 to 28.8, indicating better cognitive function. These results suggest that GlyNAC may help protect against age-related cognitive decline and neurodegenerative diseases.

Before supplementation, older adults had lower grip strength and slower walking speeds. After 24 weeks of GlyNAC, their grip strength improved, and their gait speed matched that of younger adults. These improvements suggest that GlyNAC may help reduce frailty and improve physical performance in aging individuals.

Twelve weeks after discontinuing GlyNAC, most of the improvements were lost. Oxidative stress increased again, mitochondrial function declined, inflammation worsened, and insulin resistance returned. Cognitive and physical improvements also faded. This indicates that continuous GlyNAC supplementation may be necessary to maintain its benefits.

The findings suggest that GlyNAC could be a powerful strategy for promoting healthy aging. By restoring glutathione levels and reducing oxidative stress, GlyNAC helps improve multiple aspects of health, including energy production, inflammation control, cognitive function, and muscle strength.

Because GlyNAC consists of two naturally occurring nutrients, it was well tolerated with no reported side effects. This makes it a safe and effective potential intervention for addressing aging-related health problems.

This scientific study provides strong evidence that GlyNAC supplementation may effectively combat aging-related health issues. GlyNAC offers potential benefits for brain health, muscle strength, and metabolic function by increasing glutathione levels, reducing oxidative stress, and improving mitochondrial function.

However, more research is needed to confirm these findings in larger studies and explore the long-term effects of GlyNAC supplementation. If future studies support these results, GlyNAC could become a key tool for slowing aging and reducing the risk of age-related diseases.