GlyNAC Supplementation Improves Aging Hallmarks in Older Adults: RCT

Aging is linked to increased oxidative stress, mitochondrial dysfunction, inflammation, and a decline in physical performance, all of which contribute to age-related diseases. In the study “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,” Kumar et al. investigated whether GlyNAC supplementation could counteract these aging-related defects. The researchers conducted a randomized, double-blind, placebo-controlled trial at Baylor College of Medicine, examining how GlyNAC affects glutathione levels, oxidative stress, mitochondrial function, and overall physical health in older adults. Previous studies in aged mice had shown promising results, but this study provided the first human clinical evidence that GlyNAC may help reverse multiple hallmarks of aging, improving health and function in older adults.

Aging brings many changes to the body, affecting everything from muscle strength to how cells produce energy. Scientists have long been searching for ways to slow down or even reverse some of these effects. This clinical study tested the benefits of GlyNAC, a combination of glycine and N-acetylcysteine (NAC), to see if it could improve key markers of aging in older adults.

The results? GlyNAC supplementation significantly improved oxidative stress, mitochondrial function, inflammation, and physical performance—factors that play a major role in aging. This study offers accurate clinical data suggesting that GlyNAC may help support healthier aging.

Aging is more than just getting older—it involves many biological changes that can lead to declining health. As people age, they often experience:

• Increased oxidative stress (damage from harmful molecules called free radicals)
• Declining mitochondrial function (cells lose efficiency in producing energy)
• Higher inflammation (linked to many age-related diseases)
• Weaker muscles and slower movement
• Insulin resistance (which can lead to diabetes)

One key problem in aging is the loss of glutathione (GSH), the body’s most powerful antioxidant. GSH helps neutralize oxidative stress, protects mitochondria, and supports overall health. Research shows older adults have lower GSH levels, making it harder for their bodies to fight cellular damage.

This study aimed to find out if supplementing with GlyNAC—which provides the amino acids needed to make glutathione—could reverse these aging-related problems. Previous studies in aged mice showed that GlyNAC improved oxidative stress, insulin resistance, and mitochondrial function, but no clinical trial had tested its effects in humans.

This was a randomized, double-blind, placebo-controlled clinical trial, which is one of the most reliable ways to test whether a treatment works. The study was conducted at Baylor College of Medicine and involved two groups of participants:

• 24 older adults (OA), aged 61 to 80
• 12 young adults (YA), aged 21 to 40

The older adults were randomly assigned to one of two groups:

• GlyNAC group (N=12): Took GlyNAC supplements for 16 weeks.
• Placebo group (N=12): Took an isonitrogenous alanine placebo for 16 weeks.

The young adults received GlyNAC for two weeks to compare their results with the older adults.

Participants were tested at the start, after two weeks, and after 16 weeks. Researchers measured:

• Glutathione levels in muscle and red blood cells
• Oxidative stress markers in the blood
• Mitochondrial function, including energy production
• Insulin resistance and inflammation levels
• Endothelial function, important for heart and blood vessel health
• Physical performance, including gait speed, grip strength, and a six-minute walking test

All participants were blinded to the supplement they received to ensure unbiased results.

Before taking GlyNAC, older adults had 66% lower muscle glutathione levels than young adults. However, after 16 weeks of GlyNAC supplementation, GSH levels increased by 164%, restoring them to youthful levels.

Oxidative stress was also much higher in older adults before treatment. The study found that levels of thiobarbituric acid-reactive substances (TBARS)—a marker of oxidative stress—were over 400% higher in older adults than in young adults. After GlyNAC supplementation, TBARS levels decreased by 72%, indicating a significant reduction in oxidative stress.

"Older adults had significantly elevated oxidative stress compared to young adults. GlyNAC supplementation effectively lowered these levels, demonstrating a reduction in cellular damage," the study states.

Mitochondria, often called the "powerhouses of the cell," are responsible for producing energy. As people age, mitochondrial function declines, leading to fatigue and weakness.

Before GlyNAC treatment, older adults had 42% lower mitochondrial fatty acid oxidation (a measure of how well cells produce energy). However, after 16 weeks of GlyNAC supplementation, mitochondrial function improved by 78%, bringing it closer to youthful levels.

The study also found that mitochondrial glucose oxidation (the process of using glucose for energy) was 144% higher in older adults before treatment, which is a sign of mitochondrial dysfunction. After GlyNAC, glucose oxidation dropped by 65%, indicating improved energy metabolism.

Aging often leads to weaker muscles and slower movement. This study measured physical performance using tests like walking speed, grip strength, and a six-minute walking test.

Before treatment, older adults had slower gait speed and lower muscle strength compared to young adults. After GlyNAC supplementation:

• Walking speed increased to youthful levels
• Upper and lower body strength improved
• Six-minute walking test distance increased

"These improvements suggest that GlyNAC enhances both muscle function and endurance in older adults," the study noted.

Inflammation plays a key role in aging and chronic diseases like diabetes and heart disease. The study found that key inflammatory markers, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were significantly lower after GlyNAC supplementation.

Insulin resistance, which can lead to diabetes, also decreased dramatically after 16 weeks of GlyNAC. This suggests that GlyNAC may help regulate blood sugar and reduce the risk of metabolic diseases.

The endothelium is a thin layer of cells that line blood vessels and help regulate circulation. Poor endothelial function is linked to high blood pressure and cardiovascular disease.

The study found that GlyNAC improved endothelial function, reducing markers of vascular dysfunction. This suggests that GlyNAC could help protect the heart and blood vessels.

The researchers also looked at the " hallmarks of aging ," including cellular stress, mitochondrial biogenesis (creating new mitochondria), and molecular repair processes.

After GlyNAC supplementation, older adults showed improvements in key proteins that regulate mitochondrial energy production and cellular repair. These changes indicate that GlyNAC is not just improving symptoms of aging but may be targeting the underlying biological processes that drive aging.

This study provides strong evidence that GlyNAC supplementation can reverse several aging-related problems, including oxidative stress, mitochondrial dysfunction, and inflammation.

"By combining the benefits of glycine, NAC, and GSH, GlyNAC is an effective nutritional supplement that improves and reverses multiple age-associated abnormalities," the study states.

Since aging is a significant risk factor for chronic diseases like diabetes, heart disease, and neurodegenerative conditions, improving these biological markers could have wide-ranging health benefits.

This clinical study suggests that GlyNAC supplementation may help older adults regain youthful glutathione levels, reduce oxidative stress, and improve mitochondrial function, muscle strength, and inflammation levels. Unlike many anti-aging products that lack scientific evidence, this study provides real clinical trial data showing measurable improvements in aging markers.

While more long-term studies are needed, these findings highlight GlyNAC’s potential as a powerful nutritional strategy for aging. If you’re looking for ways to support your body’s natural defenses against aging, GlyNAC could be a promising option.