Longevity experts extol the value of strength training, improved nutrition, sleep, and stress management, but supplements are also being studied for specific benefits at the cellular level. What is the benefit of taking glycine (Gly) and N-acetyl-cysteine (NAC)? What is the evidence that GlyNAC can increase longevity?
Aging is related to declining cognition and physical capacity, and increased risk of inflammation, insulin resistance, and obesity.
Mitochondria are the cellular engines which produce energy for life.
Certain age-related impairments may be connected to mitochondrial dysfunction.
Another theory of aging relates to oxidative stress during energy generation.
Two amino acids — glycine and cysteine — are used to build an important repair molecule, an antioxidant called glutathione.
Taking glycine (Gly) and N-acetyl-cysteine (NAC) or GlyNAC may boost glutathione levels and reduce the stress of aging on cells.
How aging affects cellular energy
Some researchers interested in longevity have focused their work in two key areas: mitochondrial function to produce energy and removing the toxic waste byproducts of energy production.
Think of the mitochondria as cellular batteries that produce the energy we need for life. Having healthy mitochondria is critical for our long-term well-being. With age, the mitochondria may become less efficient. This finding prompted recent research on GlyNAC to investigate whether it can improve mitochondrial function and promote a longer, healthier life.
The second age-related challenge is cleaning up the potentially toxic residues created by energy production. These 'free radicals' may cause something called 'oxidative stress', which damages cells, membranes, lipids, proteins, and DNA. This oxidative stress is very common in aging. Glutathione (GSH) is an antioxidant made by our cells and may help protect them against oxidative stress, however, glutathione levels are much lower in older people.
How to evaluate research data
The gold standard for good evidence is the randomized controlled trial (RCT). This type of trial is important because it randomizes factors that might influence the outcome across both the treatment group receiving the supplement and the control group which did not receive the supplement.
Randomization allows us to see how much effect the supplement has while adjusting for unknown or unmeasurable factors which might also affect the outcome.
A decade ago, a study in aging mice found that glutathione is very important for mitochondrial function. More recent studies have focused on evaluating the benefit of glutathione for human brain function, physical capacity, obesity, insulin resistance, and mitochondrial function.
What evidence suggests GlyNAC is beneficial?
To test whether there is any benefit to supplementing with GlyNAC in humans, a recent RCT at Baylor College of Medicine was conducted over 36 weeks. The researchers recruited five women and three men ages 71 to 80 years, plus eight young adults ages 21 to 30 years. The participants did not have chronic conditions and were non-smokers with no abnormal lab tests.
The study participants were told to eat normally but refrain from alcohol while they received GlyNAC supplementation for 24 weeks. They were followed for an additional 12 weeks to look for wash-out effects after the supplementation period ended.
The study collected blood and urine samples and performed cognitive and physical function tests at baseline, again at 12 weeks (study midpoint), and at the end of the study (24 weeks). Data was also collected on body composition, glutathione concentration, and biomarkers of inflammation. The young adults did not receive supplementation but went through all the testing.
GlyNAC supplementation appears to have increased GSH concentrations in older adults by 200% and declined once supplementation ended. Markers for oxidative stress reduced during the study period but bounced back after supplementation stopped. Although this study has produced optimistic results, additional research is still needed.
How does GlyNAC affect human aging?
In a larger follow-up study led by the same team, this time double-blinded in addition to placebo-controlled, the researchers found that GlyNAC for 16 weeks increased glutathione concentrations and improved certain aging biomarkers.
The oxidative stress markers among the older adults dropped by 42% within two weeks and reached the same levels as the young adults within 16 weeks. Muscle strength, gait speed, exercise capacity, waist circumference, and blood pressure were also reported to be improved in older adults after GlyNAC supplementation.
The muscle tissue of the older adults taking GlyNAC showed improvements that were similar to what the Baylor team found in their preliminary mouse model. These two studies suggest that taking GlyNAC may have positive effects on cellular function in many different organ systems.
Is GlyNAC safe?
The blood tests conducted among the older adults in the Baylor study found no increases in liver function tests compared to placebo. The caveat here is the study was very small and only powered to detect a statistically significant change in blood levels of glutathione.
The younger adults were not given GlyNAC; thus, we do not have data on safety in a population younger than the participants in this study, who were, on average, 71.
What about taking NAC alone?
Cells do need some ROS to allow them to function and communicate. Too much ROS results in 'reductive stress.' Supplementing with NAC alone resulted in accelerated aging in a worm (C elegans), but GlyNAC supplementation in mice increased longevity.
The clinical trial found that GlyNAC in older adults lowered oxidative stress markers, but these did not decrease below the levels found in the young adult comparison group, avoiding the risk of reductive stress and accelerated aging.
Why does GlyNAC work?
The amino acids glycine and cysteine can be made by the body, but supplementation may correct deficiencies found in older adults. These two amino acids are important for GSH synthesis. Taking NAC alone or GSH alone does not seem to offer the same benefits as taking GlyNAC, which provides glycine and cysteine for the GSH production pipeline. These two amino acids are needed for multiple cellular reactions in addition to being building blocks for GSH.
How long should one take GlyNAC?
When the supplementation is discontinued, the biomarkers for aging go back to their baseline. These data suggest that long-term supplementation with GlyNAC may be beneficial for older adults.
Should younger adults supplement with GlyNAC?
There is no safety data on younger adults, and no evidence that GlyNAC supplementation is necessary. The building block amino acids — glycine and cysteine — are made by the body naturally.
The best way to ensure adequate mitochondrial function in younger adults is to eat a well-balanced diet of whole foods, which promote a diverse microbiome capable of extracting essential micronutrients.
Incorporating fermented foods like kefir, kimchi, yogurt, kombucha, sauerkraut, and miso provides the live microbes (probiotics) necessary for good gut health.
In addition, eating a diet rich in prebiotics, such as fruits, vegetables, barley, oats, whole grains, and soybeans, provides the microbes with the soluble fibers so important to fermentation and micronutrient extraction.
What supplements make sense for older adults to take?
While the best way to get enough vitamins, minerals, and antioxidants is to eat a well-balanced diet rich in whole foods, however in some cases, even the best diet may not provide enough essential nutrients. Therefore it is essential to consult with a healthcare provider or a dietitian, which nutrients may be lacking in your diet and can be potentially beneficial if supplemented.
Legal status of GlyNAC
It is important to be aware that GlyNAC products include the ingredient N-acetyl-cysteine (NAC), which is excluded from the definition of a dietary supplement as it is an approved drug compound.
In 2022, the FDA released updated guidance for the industry, informing them of their decision to exercise enforcement discretion with respect to the sale and distribution of products that contain NAC, such as GlyNAC.
Additionally, the agency has updated their 2023 fall/winter agenda to include a review of literature on NAC safety studies. If there is sufficient evidence, the agency might update the status of NAC and products containing NAC in the near future, allowing for such products to be legally sold as dietary supplements.
- Aging Cell. Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione.
- Clinical and Translational Medicine. 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.
- The Journals of Gerontology. 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.
- Frontiers in Nutrition. Effects of N-acetylcysteine on aging cell and obesity complications in obese adults: a randomized, double-blind clinical trial.