What Is It?

N-acetylcysteine, or NAC, is an amino acid, cysteine, with an acetyl group attached to it, which makes it more bioavailable. More importantly, it acts as a building block for a vital antioxidant made by our bodies—glutathione. This internally-made, or “endogenous,” antioxidant has many critical roles: it is present in all the cells in our bodies, where it protects them from free radical damage (i.e., oxidative stress); it helps detox heavy metals like mercury and lead; it helps regenerate the antioxidant vitamins E and C; it’s critical for normal detoxification in the liver and kidneys; and is vital for mitochondrial health, the energy-making “machines” in our cells. When glutathione levels are low, health issues arise. Glutathione depletion is implicated in chronic diseases like Alzheimer’s and Parkinson’s, lung and liver diseases, cardiovascular disease, age-related diseases like macular degeneration and arthritis, and even the “aging process itself.”^{2 3 4 5}

But if our bodies make glutathione, why do we need NAC? It’s pretty simple: Our modern lives, punctuated with diets of ultra-processed foods, lack of quality sleep, chronic stress, exposure to environmental toxins, drinking alcohol, smoking, and even the aging process, continuously deplete glutathione levels. On top of that, some people just can’t efficiently make enough of it. NAC provides a bioavailable form of cysteine that is rapidly absorbed by cells, where it is used to make glutathione, efficiently increasing and maintaining levels.^{6 7} And this is where the benefits begin.

NAC Is One of Your Best Defenses During Cold & Flu Season

By increasing glutathione levels, NAC naturally benefits immunity, but research has shown that NAC itself has a balancing effect on the immune system and helps to counteract age-related decline in immunity. A recent study supplemented 36 healthy postmenopausal women (50 and older) with 600mg of NAC daily for four months. At the end of four months, there was a significant improvement in immune cell function, a reduction in inflammatory cytokines, and increases in glutathione levels inside immune cells, bringing the older women’s immune function closer to that of the younger control group (women 30-49 years old). The benefits were still measurable three months after the end of the supplementation, suggesting that NAC has a lasting effect.⁸

Other research has suggested that NAC has the ability to interfere with the flu virus’s ability to replicate and spread.^{9 10} In fact, when it comes to fighting the flu, NAC may just be one of our best defenses. One placebo-controlled study including 262 men and women 65 and older found that 600mg of NAC twice daily for six months (during flu season) resulted in “a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group.”¹¹ And more recently, research is finding that NAC can play a protective role during COVID infection, due in part to its antioxidant, anti-inflammatory, and immune-balancing effects, which helps counteract the excessive immune activation, increased inflammation, and the oxidative damage COVID causes.¹² Preliminary research also indicates that NAC may be able to interfere with the virus’s ability to replicate.¹³

Our Lungs Love NAC!

NAC was first discovered to have mucolytic—mucus thinning—properties in the 1960s, leading to a burst of research specifically looking at its effect on pulmonary diseases, diseases that affect the lungs. Since then, the research has expanded and found that NAC is beneficial in other chronic respiratory issues, like chronic obstructive pulmonary disease (COPD), and also protects our lungs from environmental toxins like air pollution.^{14 15 16}

Like any chronic disease, lung disease has an underlying factor of excessive oxidative stress and inflammation, which depletes glutathione reserves in lung cells and damages delicate tissues.¹⁷ The respiratory system is particularly susceptible to oxidative injury, both from the high levels of oxygen in the lungs as well as from external pollutants like cigarette smoke, wildfire smoke, and diesel exhaust, which also increase inflammation. NAC directly counteracts this with its ability to replenish glutathione levels, restoring antioxidant balance. In clinical settings, it has been shown that oral administration of 600mg of NAC for five days significantly increased glutathione levels in lung fluid.

Chronic obstructive pulmonary disease (COPD) is caused by damage to the airways, which leads to inflammation and restricted air flow, making it hard to breathe. It’s most often caused by smoking, but can also be caused by long-term exposure to other fumes, smoke, or chemicals. The most common types are chronic bronchitis and emphysema.¹⁸ Multiple studies have found that daily supplementation with 600-1,200mg of NAC reduces harmful free radicals and inflammatory markers and significantly reduces flare-ups in subjects with COPD.¹⁹ A 2024 meta-analysis, including 20 randomized, controlled trials and 4,044 subjects with either chronic bronchitis or some other form of COPD, evaluated the effects of daily supplementation with NAC (doses ranged from 400-3,600mg). The subjects treated with NAC experienced fewer flare-ups, significantly fewer symptoms, and overall better quality of life.²⁰ Another study investigating NAC and chronic bronchitis found that 400mg per day administered during the winter months lead to a significant reduction in flare-ups, a significantly smaller percentage of “sick days” from work, and lower rates of hospitalizations.²¹

Exposure to air pollution, like wildfire smoke or car exhaust, can lead to the same damage as chronic lung disease—increases in oxidative damage and inflammation and reductions in glutathione. The research in this area is still fairly new, but results so far are promising. A 2022 study found that NAC reduced lung injury caused by fine particulate matter in exposed mice, reducing oxidative damage and lung inflammation.²² Fine particulate matter is particularly harmful because it can infiltrate deep into the lungs; one common source is car exhaust. A placebo-controlled trial including 13 patients with mild asthma found that 600mg of NAC three times a day, taken for five days leading up to exposure, reduced the oxidative damage and inflammation caused by diesel exhaust.²³

NAC Helps the Liver Function Its Best

Perhaps one of NAC’s most well-known uses is supporting liver health and detoxification. In fact, NAC is the first-line treatment for acetaminophen overdose, in which glutathione is quickly depleted in the liver, leading to major oxidative damage and mitochondrial dysfunction, which can cause acute liver injury and even death from acute liver failure. Administration of NAC in cases of acetaminophen overdose rapidly increases glutathione synthesis in the liver, increases the supply of oxygen to the liver, and reduces mitochondrial damage.^{24 25} NAC has also been used to effectively counteract mushroom, pesticide, and chloroform poisoning to prevent acute liver damage.^{26 27}

NAC also provides support in cases of chronic liver disease, such as non-alcoholic fatty liver disease (NAFLD), a growing health concern linked to a diet high in ultra-processed foods, in which excessive amounts of fat accumulate in the liver, driving oxidative damage and inflammation that can eventually lead to liver failure if left unchecked. A 2019 randomized controlled study found that daily supplementation of 1,200mg of NAC plus metformin in subjects with NASH (the most severe form of NAFLD) for about 11 months significantly improved liver fat, cell injury, markers of liver damage, and overall disease severity.²⁸ Unfortunately, NAFLD is a growing problem among children too, and a pilot study published in 2024 tested the effect of either 600mg or 1,200mg of daily NAC against a placebo in 13 children with NAFLD. Sixteen weeks of treatment with NAC (either dose) improved markers of inflammation, oxidative stress, and insulin resistance and reduced liver enzymes associated with liver damage, liver stiffness, and liver fat. The researchers also noted that NAC was “well tolerated” among the children.²⁹

And finally, NAC is critical to the body’s natural everyday detoxification processes. NAC directly neutralizes the free radicals produced during cellular and liver detoxification processes, and it rapidly replenishes the glutathione that is used to remove toxins from the body. In short, NAC not only helps eliminate harmful compounds from the body, but also protects the liver from injury during the detoxification process.

Metabolic Health, PCOS, and So Much More…

NAC’s benefits go on… and on… A small study including 35 patients with diagnosed metabolic syndrome (a cluster of metabolic abnormalities including high blood pressure, obesity, insulin resistance, and high triglycerides that are strongly associated with a risk of cardiovascular disease) found that 600mg of NAC twice daily for six weeks improved insulin resistance, blood pressure, triglyceride levels, and measures of inflammation. The researchers concluded, “This study has provided a new approach of management of MetS with NAC beyond controlling the disease with various drug therapies.”³⁰ Polycystic ovary syndrome (PCOS) is another metabolic disorder specifically affecting women of reproductive age that can include abnormal ovulation, elevated levels of testosterone, infertility, obesity, and insulin resistance. A meta-analysis including 11 randomized controlled trials found that NAC (at a dose of 1,500mg per day) improved body weight, fasting insulin, fasting blood glucose, total cholesterol, and triglycerides compared with metformin (commonly used to treat PCOS), overall improving the metabolic parameters in women with PCOS.³¹

NAC has also been successfully used to reduce cravings in substance abuse disorders;³² there is evidence that NAC may be protective in neurodegenerative diseases like Parkinson’s and Alzheimer’s;³³ research indicates that NAC may be therapeutic in mental health disorders including bipolar disorder, schizophrenia, and obsessive compulsive disorders;³⁴ and finally, multiple studies point to NAC’s potential in cardiovascular disease, including improving atherosclerosis and heart failure.^{35 36} Truly, a necessary supplement for our modern lives!

References

1. Alam, M. S., Hasan, M. N., Maowa, Z., Khatun, F., Nazir, K. H. M. N. H., & Alam, M. Z. (2023). N-acetylcysteine reduces severity and mortality in COVID-19 patients: A systematic review and meta-analysis. Journal of advanced veterinary and animal research, 10(2), 157–168. https://doi.org/10.5455/javar.2023.j665
2. Pizzorno J. (2014). Glutathione!. Integrative medicine (Encinitas, Calif.), 13(1), 8–12.
3. Matuz-Mares, D., Riveros-Rosas, H., Vilchis-Landeros, M. M., & Vázquez-Meza, H. (2021). Glutathione Participation in the Prevention of Cardiovascular Diseases. Antioxidants (Basel, Switzerland), 10(8), 1220. https://doi.org/10.3390/antiox10081220
4. Wu, G., Fang, Y. Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of nutrition, 134(3), 489–492. https://doi.org/10.1093/jn/134.3.489
5. Julius, Mara et al. Glutathione and morbidity in a community-based sample of elderly Journal of Clinical Epidemiology, Volume 47, Issue 9, 1021 - 1026
6. Rushworth, Gordon F.; Megson, Ian L. (2014). Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits. Pharmacology & Therapeutics, 141(2), 150–159. doi:10.1016/j.pharmthera.2013.09.
7. Santus, P., Corsico, A., Solidoro, P., Braido, F., Di Marco, F., & Scichilone, N. (2014). Oxidative stress and respiratory System: Pharmacological and clinical reappraisal of N-Acetylcysteine. COPD Journal of Chronic Obstructive Pulmonary Disease, 11(6), 705–717. https://doi.org/10.3109/15412555.2014.898040
8. Arranz, L., Fernández, C., Rodríguez, A., Ribera, J. M., & De la Fuente, M. (2008). The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free radical biology & medicine, 45(9), 1252–1262. https://doi.org/10.1016/j.freeradbiomed.2008.07.014
9. Tieu, S., Charchoglyan, A., Paulsen, L., Wagter-Lesperance, L. C., Shandilya, U. K., Bridle, B. W., Mallard, B. A., & Karrow, N. A. (2023). N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants, 12(10), 1867. https://doi.org/10.3390/antiox12101867
10. Schwalfenberg G. K. (2021). N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). Journal of nutrition and metabolism, 2021, 9949453. https://doi.org/10.1155/2021/9949453
11. De Flora, S., Grassi, C., & Carati, L. (1997). Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. European Respiratory Journal, 10(7), 1535–1541. https://doi.org/10.1183/09031936.97.10071535
12. Tieu, S., Charchoglyan, A., Paulsen, L., Wagter-Lesperance, L. C., Shandilya, U. K., Bridle, B. W., Mallard, B. A., & Karrow, N. A. (2023). N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants, 12(10), 1867. https://doi.org/10.3390/antiox12101867
13. Debnath, U., Mitra, A., Dewaker, V., Prabhakar, Y. S., Tadala, R., Krishnan, K., Wagh, P., Velusamy, U., Baliyan, A., Kurpad, A. V., Bhattacharyya, P., & Mandal, A. K. (2023). Conformational perturbation of SARS-CoV-2 spike protein using N-acetyl cysteine: an exploration of probable mechanism of action to combat COVID-19. Journal of Biomolecular Structure and Dynamics, 42(10), 5042–5052. https://doi.org/10.1080/07391102.2023.2234031
14. Schwalfenberg G. K. (2021). N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). Journal of nutrition and metabolism, 2021, 9949453. https://doi.org/10.1155/2021/9949453
15. Tieu, S., Charchoglyan, A., Paulsen, L., Wagter-Lesperance, L. C., Shandilya, U. K., Bridle, B. W., Mallard, B. A., & Karrow, N. A. (2023). N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants, 12(10), 1867. https://doi.org/10.3390/antiox12101867
16. Tenório, M. C. D. S., Graciliano, N. G., Moura, F. A., Oliveira, A. C. M., & Goulart, M. O. F. (2021). N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants (Basel, Switzerland), 10(6), 967. https://doi.org/10.3390/antiox10060967
17. Tieu, S., Charchoglyan, A., Paulsen, L., Wagter-Lesperance, L. C., Shandilya, U. K., Bridle, B. W., Mallard, B. A., & Karrow, N. A. (2023). N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants, 12(10), 1867. https://doi.org/10.3390/antiox12101867
18. COPD - Symptoms and causes. (n.d.). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/copd/symptoms-causes/syc…
19. Santus, P., Corsico, A., Solidoro, P., Braido, F., Di Marco, F., & Scichilone, N. (2014). Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine. COPD, 11(6), 705–717. https://doi.org/10.3109/15412555.2014.898040
20. Papi, A., Alfano, F., Bigoni, T., Mancini, L., Mawass, A., Baraldi, F., Aljama, C., Contoli, M., & Miravitlles, M. (2024). N-acetylcysteine treatment in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis/Pre-COPD: distinct meta-analyses. Archivos De Bronconeumología, 60(5), 269–278. https://doi.org/10.1016/j.arbres.2024.03.010
21. Grandjean, E. M., Berthet, P. H., Ruffmann, R., & Leuenberger, P. (2000). Cost-effectiveness analysis of oral N-acetylcysteine as a preventive treatment in chronic bronchitis. Pharmacological research, 42(1), 39–50. https://doi.org/10.1006/phrs.1999.0647
22. Lin, C., Huang, T., Chi, M., Guo, S., Lee, C., Hwang, S., & Shi, C. (2022). N-acetylcysteine alleviates fine particulate matter (PM2.5)-induced lung injury by attenuation of ROS-mediated recruitment of neutrophils and Ly6Chigh monocytes and lung inflammation. Ecotoxicology and Environmental Safety, 239, 113632. https://doi.org/10.1016/j.ecoenv.2022.113632
23. Yamamoto, M., Singh, A., Sava, F., Pui, M., Tebbutt, S. J., & Carlsten, C. (2013). MicroRNA expression in response to controlled exposure to diesel exhaust: attenuation by the antioxidant N-acetylcysteine in a randomized crossover study. Environmental health perspectives, 121(6), 670–675. https://doi.org/10.1289/ehp.1205963
24. Tieu, S., Charchoglyan, A., Paulsen, L., Wagter-Lesperance, L. C., Shandilya, U. K., Bridle, B. W., Mallard, B. A., & Karrow, N. A. (2023). N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals. Antioxidants, 12(10), 1867. https://doi.org/10.3390/antiox12101867
25. Tenório, M. C. D. S., Graciliano, N. G., Moura, F. A., Oliveira, A. C. M., & Goulart, M. O. F. (2021). N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants (Basel, Switzerland), 10(6), 967. https://doi.org/10.3390/antiox10060967
26. Schwalfenberg G. K. (2021). N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). Journal of nutrition and metabolism, 2021, 9949453. https://doi.org/10.1155/2021/9949453
27. El‐Ebiary, A. A., Elsharkawy, R. E., Soliman, N. A., Soliman, M. A., & Hashem, A. A. (2016). N‐acetylcysteine in acute organophosphorus pesticide poisoning: a randomized, clinical trial. Basic & Clinical Pharmacology & Toxicology, 119(2), 222–227. https://doi.org/10.1111/bcpt.12554
28. Oliveira, C. P., Cotrim, H. P., Stefano, J. T., Siqueira, A. C. G., Salgado, A. L. A., & Parise, E. R. (2019). N-Acetylcysteine And/Or Ursodeoxycholic Acid Associated With Metformin In Non-Alcoholic Steatohepatitis: An Open-Label Multicenter Randomized Controlled Trial. Arquivos de gastroenterologia, 56(2), 184–190. https://doi.org/10.1590/S0004-2803.201900000-36
29. Babu Balagopal, P., Kohli, R., Uppal, V., Averill, L., Shah, C., McGoogan, K., Di Guglielmo, M., Goran, M., & Hossain, M. J. (2024). Effect of N-acetyl cysteine in children with metabolic dysfunction-associated steatotic liver disease-A pilot study. Journal of pediatric gastroenterology and nutrition, 79(3), 652–660. https://doi.org/10.1002/jpn3.12312
30. Rani, M., Aggarwal, R., & Vohra, K. (2020). Effect of N-Acetylcysteine on metabolic profile in metabolic syndrome patients. Metabolic Syndrome and Related Disorders, 18(7), 341–346. https://doi.org/10.1089/met.2020.0017
31. Liu, J., Su, H., Jin, X., Wang, L., & Huang, J. (2023). The effects of N-acetylcysteine supplement on metabolic parameters in women with polycystic ovary syndrome: a systematic review and meta-analysis. Frontiers in Nutrition, 10, 1209614. https://doi.org/10.3389/fnut.2023.1209614
32. Morley, K. C., Baillie, A., Van Den Brink, W., Chitty, K. E., Brady, K., Back, S. E., Seth, D., Sutherland, G., Leggio, L., & Haber, P. S. (2018). N-acetyl cysteine in the treatment of alcohol use disorder in patients with liver disease: Rationale for further research. Expert Opinion on Investigational Drugs, 27(8), 667–675. https://doi.org/10.1080/13543784.2018.1501471
33. Tardiolo, G., Bramanti, P., & Mazzon, E. (2018). Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules (Basel, Switzerland), 23(12), 3305. https://doi.org/10.3390/molecules23123305
34. Schwalfenberg G. K. (2021). N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). Journal of nutrition and metabolism, 2021, 9949453. https://doi.org/10.1155/2021/9949453
35. Yazdi, A., Khansari, N., Mehrpooya, M., Mohammadi, Y., & Zareie, S. (2022). Oral N-acetylcysteine as an adjunct to standard medical therapy improved heart function in cases with stable class II and III systolic heart failure. Irish journal of medical science, 191(5), 2063–2075. https://doi.org/10.1007/s11845-021-02829-3
36. Cui, Y., Zhu, Q., Hao, H., Flaker, G. C., & Liu, Z. (2023). N-Acetylcysteine and Atherosclerosis: Promises and Challenges. Antioxidants (Basel, Switzerland), 12(12), 2073. https://doi.org/10.3390/antiox12122073