Amino acids and NRF2 activation: A new strategy for healthy aging?

NRF2 is a standout pathway in the sphere of age-related research. NRF2 (nuclear factor erythroid 2-related factor 2) is a transcription factor that helps control the body’s response to oxidative stress, a contributor to many processes related to aging. On a biochemical level, NRF2 regulates protein-to-protein interactions in antioxidant systems like glutathione and its related enzymes. Emerging research suggests that certain micronutrients, including amino acids obtained through common dietary sources including leafy greens, vegetables, and certain animal proteins, may help support longevity through the NRF2 pathway.

A 2024 review article by Egbujor and colleagues explored the potential impact of amino acids on the NRF2 pathway. In addition, while many amino acids influence the NRF2 pathway, the authors suggest there is a bidirectional relationship–meaning that the NRF2 pathway also influences amino acid activity. For instance, NRF2 influences glutamine uptake, the TCA cycle, and metabolism. NRF2 also modulates the availability of amino acids for use in the body through its influence on transcription, transporters, and other aspects of amino acid biosynthesis.   

Glycine is the smallest amino acid and is a major component of collagen. It also acts as a calming neurotransmitter; clinical studies suggest that glycine may support certain aspects of sleep efficiency. In laboratory and animal studies, glycine was observed to help activate the NRF2 pathway and influence certain aspects of cellular health. Dietary sources of glycine include collagen-rich animal protein sources, dairy, and certain legumes.*  

N-acetyl cysteine (NAC) is a derivative of the amino acid cysteine. Cysteine is a building block for glutathione, the body’s master antioxidant agent. NAC is a more biostable form of cysteine and has been shown to help activate NRF2 pathways. In a clinical study, oral NAC supplementation was shown to help increase the expression of NRF2 genes and enzymes related to antioxidant activity.*  

Taurine, often studied for its role in healthy aging, supports mitochondrial function and cellular health. It helps support mitochondrial homeostasis and many other aspects of cellular health. On the biochemical level, taurine has been shown in animal studies to help activate the NRF2/HO-1 signaling pathway and help support antioxidative status. Taurine can be found in certain meats, fish, and dairy products.*   

Tryptophan is a well-known precursor for melatonin synthesis. It also supports serotonin and NAD biosynthesis. Animal studies suggest that tryptophan may also activate the NRF2 pathway, suggesting that tryptophan has many supportive actions in the body related to longevity and overall wellness.*  

While more research is needed, particularly in the clinical setting, amino acids may help support optimal NRF2 activity. In turn, NRF2 activity may help optimize amino acid availability in the body–both of which may help support vitality and healthy aging.* 

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* These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.