The Power of Three: How Glutathione, Glycine, and NAC Support Strong Bodies and Minds With Age

With increasing age comes a whole host of changes to the body.  These changes start internally, causing organ dysfunction and disease, while eventually manifesting as external aging. From declines in cognitive function to diminished muscle mass to increased inflammation, aging is characterized by a myriad of markers of degrading health.

While there are potentially many causes of these internal age-related defects, low levels of the antioxidant glutathione are thought to be a leading suspect. As glutathione levels markedly decrease with age, our bodies become less able to fight off damage and inflammation inside our cells — leading to much of the declines in heart, brain, muscle, immune, and metabolic health commonly found in older adults. If low glutathione levels are the problem, it may seem like simply adding more of the antioxidant could be a panacea for reversing these age-related health problems. However, most forms of glutathione supplements exhibit poor bioavailability — meaning, your body can’t readily absorb and utilize it.

Aiming to circumvent this issue, researchers out of Baylor College of Medicine in Houston, Texas, tested a supplement that instead uses two of glutathione’s precursors: the amino acids cysteine (in the form of N-acetylcysteine [NAC]) and glycine. Authored by Kumar and colleagues, this recent study published in Clinical and Translational Medicine finds that this combination supplement, coined as GlyNAC, may be just what our cells need to prevent or delay age-related dysfunction and remain healthy with each passing year.   

The Metabolic Mastery of Our Master Antioxidant 

As glutathione is referred to as our “master antioxidant,” inadequate levels of it will result in increased oxidative stress — the accumulation of inflammatory molecules called free radicals or reactive oxygen species (ROS) that damage cells, protein, fats, and DNA. Although we all create free radicals and ROS in our bodies, healthy individuals can neutralize them with antioxidants — primarily glutathione. Conversely, older adults are less able to eliminate these compounds due to inadequate glutathione, which can stem from the low availability of glycine and cysteine. 

Another hallmark of age-related physiological decline is dysfunctional mitochondria — our cells’ battery packs that create energy for all cellular processes by oxidizing (burning) fat molecules called fatty acids and glucose (sugar) from the food we eat. This process of burning food for energy naturally generates ROS, leading the mitochondria to be especially vulnerable to oxidative damage if there is insufficient glutathione around to neutralize the damaging compounds. 

Because mitochondria are dependent on glutathione, Kumar and colleagues speculate that increasing levels of this master antioxidant with GlyNAC could provide a one-two punch of reducing both the oxidative stress and mitochondrial dysfunction that cause age-related physiological decline. As proposed by the corresponding author on the study, Dr. Sekhar, "It is believed that correcting these aging hallmarks could improve or reverse many age-related disorders and help people age in a healthier way." 

GlyNAC Garners Health, From the Inside Out

In this small pilot clinical study, eight older adults between the ages of 71 and 80 took GlyNAC supplements for 24 weeks, with a 12-week post-supplementation period designed to assess if any benefits remained after stopping the treatment. Compared to a sample of eight younger adults in their 20s, the older adults had significantly altered internal markers of cell health. These abnormal markers included reduced levels of glutathione and anti-inflammatory signaling molecules called cytokines, combined with elevated levels of oxidative damage, pro-inflammatory cytokines, DNA damage, and dysregulated mitochondrial function.

After 24 weeks of supplemental GlyNAC, all of these abnormal biomarkers were reversed. Notably, the older adults’ glutathione levels doubled, translating to their markers of oxidative stress dropping by three-quarters and markers of DNA damage reducing by two-thirds. 

Although most of these markers elevated again in the 12 weeks after stopping GlyNAC supplementation, their levels of oxidative stress and inflammatory cytokines still remained much lower than pre-GlyNAC levels, suggesting that the supplement provides some long-term protection from oxidative damage and inflammation. This amelioration of oxidative stress also improved mitochondrial function, correcting the dysfunctional levels of fatty acid and glucose oxidation. 

Supporting Stronger Minds and Bodies 

The improved mitochondrial function from the boost in glutathione also translated to better physical and cognitive function, likely from the increase in energy creation from our cells’ battery packs. In the physical realm, GlyNAC supplementation reduced body fat mass by 4% and reduced waist circumference by 4 centimeters — improving two metabolic risk factors that substantially increase the risk of cardiovascular disease. Similarly, the glutathione precursors reduced fasting blood glucose levels and insulin resistance — which was almost six-fold higher than the young adults at the start of the study. 

The GlyNAC-supplemented adults also had improved markers of physical function, including stronger grip strengths, boosted exercise capacity in a walking test, and gait speed that increased to match the younger adults’ speed. However, these markers reverted to pre-supplementation levels during the 12 weeks after stopping GlyNAC.

Lastly, the glycine-NAC combination significantly boosted cognition, including their scores of verbal fluency, response speed, sustained attention, and visual-spatial skills — the ability to tell where objects are in relation to others. These improvements may be due to the older adults’ increases in BDNF (brain-derived neurotrophic factor), a protein essential for the growth, survival, and maintenance of neurons. High levels of BDNF strengthen neuroplasticity — the brain’s ability to grow and adapt by forming new neural connections — and improve memory and learning abilities.

Glutathione, Glycine, and NAC: The Future of the Power of Three

Despite its small size, the implications of this small study are potentially wide-reaching, as glycine and NAC are readily available and well-tolerated supplements. While more studies — especially randomized controlled trials — are warranted to gain more insight into how the glycine-NAC combination benefits mitochondrial, metabolic, cognitive, and physical health, these results suggest that preventing or reversing common signs of aging may soon be within reach with GlyNAC. However, it’s important to note that most of the beneficial results seen in this study were not sustained for long after the treatment ended, suggesting that intermittent or short-term GlyNAC supplementation may not be sufficient for improving health in the long term.

"The overall findings of the current study are highly encouraging," Sekhar summarizes. "They suggest that GlyNAC supplementation could be a simple and viable method to promote and improve healthy aging in older adults. We call this the 'Power of 3' because we believe that it takes the combined benefits of glycine, NAC, and glutathione to reach this far-reaching and widespread improvement. We also have completed a randomized clinical trial on supplementing GlyNAC vs. placebo in older adults, and those results will be forthcoming soon." Stay tuned!

References: 

Kumar P, Liu C, Hsu JW, et al. 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. Clin Transl Med. 2021;11(3):e372. doi:10.1002/ctm2.372