NAC can be an effective remedy for asthma, bronchitis and other respiratory conditions by clearing mucus from the lungs. Furthermore, its expectorant effect helps replenish glutathione stores as well as control glutamate levels in the brain.
NAC has been shown to extend the lives of worms, flies and mice through various hormetic mechanisms that include activating stress-responsive pathways like heat shock proteins, antioxidant enzymes and DNA repair mechanisms [2]. However, its lifespan-extending effects vary by species and gender.
1. Reduces oxidative stress
Glutathione (GSH) is the key endogenous intracellular antioxidant and its deficiency can hasten biological aging. N-acetylcysteine (NAC), one of the precursors for glutathione production, can reduce reactive oxygen species (ROS) that contribute to cell oxidative stress through studies in rodents.
NAC can restore the thiol content of mitochondrial matrix, protecting them from oxidative damage. Thus, NAC serves as an effective anti-oxidant and has been utilized as an antidote against overdose of acetaminophen, as well as being studied as potential therapy against cognitive decline where oxidative stress plays a role.
A randomized, controlled clinical trial with healthy older adults demonstrated that oral supplementation of GlyNAC significantly corrected GSH deficiency, OxS, insulin resistance, mitochondrial dysfunction, physical function, waist circumference and 7 hallmarks of aging including mitochondrial damage/oxidative DNA damage/telomere shortening/cell mitophagy/genome damage/inflammation and IR (Sekhar et al, 2021a).
In this study, 117 elderly participants aged 60-85 years were randomly assigned either placebo or 2.4, 4.8, or 7.2 grams daily of oral Glycine + NAC treatment in two doses. Primary outcomes were GSH-T levels in circulation, while concentrations of malondialdehyde and the ratio between reduced and oxidized glutathione (GSH-F/GSSG) were assessed as secondary efficacy outcomes. Glycine and NAC are quickly absorbed when taken orally, reaching blood levels within one hour at all three active doses tested. This rapid absorption can be attributed to their respective fast absorption mechanisms: Glycine’s lipid-soluble nature allows it to cross through intestinal barrier easily while water-soluble NAC readily metabolized by liver enzymes before excreting through urine.
2. Reduces inflammation
N-Acetylcysteine (NAC) is an extremely potent antioxidant that directly attacks reactive oxygen species while simultaneously stimulating GSH biosynthesis1. NAC has become a go-to treatment for acetaminophen overdose, as its antidote to restore liver function after overdose and has also been found effective against inflammation related to atherosclerosis, inflammatory bowel disease and transplant rejection – and may even benefit cognitive decline and aging where oxidative stress plays a part.
NAC can have a profound effect on cell redox balance and modulate several transcription factors. Direct scavenging of ROS by NAC has been shown to improve protein stability and cell proliferation2. On the other hand, however, NAC may act as an agonist for nuclear factor-kappaB (NF-B) pathways, leading to proinflammatory responses3.
In this study, we found that chronically supplementing worms with low molecular weight thiols (such as glutathione) significantly extended their lifespan. Subsequently, 5 mM NAC proved an extremely potent inhibitor of DAF-16 and SKN-1-regulated genes; consequently resulting in reduced endogenous cytoprotective gene networks and shorter lifespan. We speculate that its adverse effect may stem from its ability to scavenge specific parts of their thiol pool while simultaneously blunting their endogenous signaling network.
To verify that NAC had an effect solely due to its decreased thiol group, we added an equal concentration of N-acetyl serine (NAS) into their diet and found no reduction in lifespan; thus confirming NAC as having an antithiol-specific impact.
Supplementing old mice with either regular diets or GlyNAC, we measured multiple brain outcomes (GSH, OxS, mitochondrial energetics, autophagy/mitophagy, glucose transporter function, genomic damage, inflammation and neurotrophic growth factors). Our results provide proof of concept that GlyNAC supplements can enhance cognition in aging by correcting many defects associated with Alzheimer’s-like dementia (ACD). Furthermore, they reduced inflammation markers significantly as well as improving many defects related to age-related cognitive dysfunctions associated with ACD; additionally they ameliorated other defects related to natural occurring Alzheimer’s-like dementia (ACD). Furthermore, they improved functions that corresponded with reduced inflammation markers as well as amelioration of other defects related to ACD.
3. Strengthens the immune system
NAC is a powerful antioxidant, capable of neutralizing free radicals while replenishing glutathione stores naturally produced in your body. GSH plays a critical role in protein synthesis and cell redox maintenance while reducing oxidative stress and supporting healthy aging through various means. NAC has been shown to improve insulin resistance, decrease inflammation levels, treat an acetaminophen overdose intravenously, as well as reducing lung scarring from chronic obstructive pulmonary disease patients.
NAC may help protect against and treat certain cancers, such as lung tumors that form in mice with K-Ras and B-Raf1 mutations that trigger lung tumor development. Furthermore, NAC is also thought to decrease cancer cell proliferation.
4. Reduces cognitive decline
Finding ways to slow or reverse the natural decline of cognitive abilities with age is one of the greatest challenges facing medicine today. A team at Baylor College of Medicine recently demonstrated that supplementation with glycine and N-acetylcysteine, precursors of natural antioxidant glutathione, significantly improved cognitive function in old mice. They discovered this was linked to correction of various aging brain defects including oxidative stress, mitochondrial dysfunction, genomic damage, lower expression of neurotrophic factors and correction of other related problems.
Oral NAC feeding was found to restore hippocampal redox potential and protect spatial memory deficits caused by AbOs-induced downregulation of RyR2 and Arc as well as reduce frequency of RyR channels responsive to Ca2+ activation (Figure 1). Furthermore, NAC improved cognitive performance of water-restricted aged rats during an Oasis maze task with regards to both time taken and errors committed compared with controls (Figure 2).
Cognitive decline as we age may occur slowly but be hastened by life stressors or illnesses (e.g. pneumonia). While its development will eventually lead to debilitating dementia conditions, individuals can delay its onset by following healthy lifestyle habits and adopting healthier living practices.
GlyNAC supplementation significantly reversed cognitive ability decline in old mice when compared with controls and corrected multiple brain defects associated with aging, including restored mitochondrial energy, autophagy/mitophagy, glucose transporters, genomic damage and oxidative stress levels. Lowering elevated brain inflammation associated with aging likely contributed to this improvement; additionally oxidative stress reduction is thought to promote neurotrophic factors known for supporting cognitive health such as BDNF, GDNF and NGF production which in turn contribute towards cognitive enhancement.
5. Reduces heart disease
NAC supplements glutathione levels in your body – perhaps its most essential antioxidant – with replenished stores of glutathione. Glutathione helps neutralize free radicals that damage cells and tissues while supporting natural immunity and toxin removal processes in your immune system. Studies have also demonstrated its effects on improving heart disease symptoms.
NAC supplementation significantly attenuated atherosclerotic lesion progression in an animal model of atherosclerosis by suppressing pro-inflammatory cytokines and M2 macrophage polarization, as well as by decreasing LDL-cholesterol production while increasing apoptosis of vascular smooth muscle cells and decreasing CRP and IL-6 levels, thus decreasing overall inflammation levels while also neutralizing ROS production.
Other studies have demonstrated the power of NAC to regulate blood sugar and prevent HIV-1 reproduction in test-tube experiments, while also helping women living with polycystic ovary syndrome (PCOS), an hormonal condition which affects women of childbearing age.
One study showed that NAC and procysteine (another amino acid) administered intravenously improved glutathione levels among patients with acute respiratory distress syndrome (ARDS), an extreme form of lung injury. Patients receiving NAC or procysteine experienced less risk of death and reduced symptoms than those receiving placebo treatments.
NAC may help improve male fertility by stimulating production of testosterone and blocking conversion from cholesterol to triglycerides. This effect may be the result of its ability to boost antioxidant status and sperm function for men with inadequate intakes of folic acid, zinc and vitamin B12. Taking NAC may increase homocysteine levels which is associated with heart disease; to combat this it’s recommended taking multivitamins along with enough B vitamins dietary sources when taking NAC; always do this under medical advice.
