GlyNAC supplementation improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, aging hallmarks, metabolic defects, muscle strength, cognitive decline, and body composition: Implications for healthy aging
Introduction
Ageing entails a progressive decline in mitochondrial function, antioxidant defences, and metabolic health, contributing to frailty, cognitive decline, and increased disease risk. A key factor in this process is oxidative stress, which occurs when the body's natural defences, such as glutathione, become depleted, leading to cellular damage.
Recent research has identified a critical role for glycine and cysteine, two amino acids essential for glutathione synthesis. GlyNAC (a combination of glycine and N-acetylcysteine) has been proposed as a strategy to restore glutathione levels, reduce oxidative stress, and improve multiple ageing-related defects.
This review summarises human clinical trials and animal studies investigating GlyNAC’s effects on ageing hallmarks, including mitochondrial dysfunction, inflammation, and metabolic health.
What did the review examine?
This review evaluates findings from published human clinical trials and rodent studies to determine how GlyNAC supplementation affects:
- Glutathione deficiency and oxidative stress
- Mitochondrial function and energy metabolism
- Inflammation and other hallmarks of ageing
- Muscle strength, cognition, and body composition
- Insulin resistance and metabolic health
Findings
Glutathione deficiency and oxidative stress
- Older adults exhibit significantly lower glutathione levels compared to younger individuals, contributing to increased oxidative stress and cellular damage.
- GlyNAC supplementation restores glutathione levels, leading to a significant reduction in oxidative stress markers and DNA damage.
- This antioxidant effect helps protect cells from free radical-induced damage, a key driver of ageing and chronic disease.
Mitochondrial dysfunction and energy metabolism
- Mitochondrial function declines with age, impairing fatty acid oxidation and cellular energy production.
- Studies in older humans and aged rodents show that GlyNAC improves mitochondrial function and reduces metabolic defects.
- Supplementation leads to enhanced exercise capacity and muscle endurance.
Inflammation and ageing hallmarks
- Chronic low-grade inflammation ("inflammaging") accelerates ageing and is associated with cardiovascular and neurodegenerative diseases.
- GlyNAC supplementation lowers pro-inflammatory cytokines (IL-6, TNF-α, CRP) and promotes anti-inflammatory responses.
- Improvements in genomic stability, cellular senescence, and nutrient sensing pathways suggest that GlyNAC may counteract multiple ageing hallmarks.
Muscle strength, cognition, and body composition
- Muscle weakness and cognitive decline are common with ageing.
- GlyNAC improves muscle strength, gait speed, and cognitive function, with effects becoming more pronounced after 24 weeks of supplementation.
- In animal models, GlyNAC reduces muscle protein degradation, suggesting potential benefits for sarcopenia prevention.
Insulin resistance and metabolic health
- Insulin resistance increases with age, increasing the risk of type 2 diabetes and cardiovascular disease.
- Human studies suggest that GlyNAC supplementation enhances insulin sensitivity and reduces fasting blood glucose levels.
- Improvements in endothelial function and cardiovascular health suggest a protective effect against metabolic syndrome.
Why does this matter?
As average life expectancy increases, finding effective strategies to support healthy ageing is becoming increasingly important. This review shows that GlyNAC supplementation can address multiple ageing-related defects, improving glutathione levels, mitochondrial function, and metabolic health.
