In our modern world, we are exposed to vast numbers of toxins every moment of our lives. We inhale pollutants such as nitrous oxide and benzene with the air we breathe, and ingest persistent organic pollutants (POPs) such as pesticides, dioxins and PCBs from the foods we put in our mouths. Heavy metals such as lead, mercury and cadmium can build up in our bodies to dangerous levels, and our own bodies produce free radicals and toxins during normal metabolism.¹ Toxins cannot be avoided, but thankfully our bodies are equipped with the means to deal with them. Xenobiotic metabolising enzymes such as Cytochrome P450 enzymes and glutathione transferase metabolise, detoxify and excrete toxins. It is only when these detoxifying systems become overwhelmed that disease and ill-health ensues.¹ It is therefore vitally important to ensure that we support our natural protective detoxification systems. A great way to do this is to supplement with N-acetylcysteine (NAC).  

Glutathione Synthesis

Much of NAC's therapeutic effect is due to its role in glutathione synthesis. Cysteine is the rate limiting nutrient in glutathione synthesis, and NAC supplementation has been shown to improve glutathione production. Glutathione is one of our most potent antioxidants and a vital detoxifier of xenobiotics and toxins. It also plays an important role in the regulation of cellular proliferation and apoptosis, mitochondrial function and DNA methylation. Disturbances in glutathione homeostasis have been implicated in neurodegenerative diseases, metabolic diseases such as diabetes and cardiovascular disease, liver disease, chronic lung conditions, autoimmunity, cancer and aging.²

NRF2 Activation

In addition to improving glutathione levels, NAC also exerts protective effects via activation of nuclear factor erythroid 2-related factor 2 (NRF2). NRF2 is a transcription factor that, when activated, up-regulates gene expression of powerful antioxidant and detoxification enzymes, including Superoxide Dismutase, Catalase and Glutathione-S-Transferase. NRF2 activation plays a significant role in protecting our cells from exposure to toxins, xenobiotics and pro-oxidants.^3,4

Heavy metal chelation

The antioxidant effects of NAC protect cells from oxidative damage induced by heavy metals. NAC can also bind to and chelate heavy metals, preventing their uptake into cells and aiding excretion.⁵ NAC has been shown to reduce markers of oxidative damage associated with lead exposure, and to reduce blood levels of lead in chronically exposed lead workers.^6,7

Hepato-protective Effects

NAC is used both orally and intravenously to prevent acute liver failure induced by paracetamol toxicity. Paracetamol is normally rapidly detoxified by glutathione; however in overdose hepatic glutathione levels are quickly depleted, and liver damage ensues. NAC reduces liver damage primarily by restoring glutathione levels.⁸ NAC is also used to treat other causes of acute liver damage, including amanita mushroom poisoning⁹, drug-induced liver injury, autoimmune hepatitis and Hepatitis B in both adults and children. ^10,11

NAC has also proven beneficial in the treatment of Non-Alcoholic Fatty Liver Disease (NAFLD), improving liver function and reducing steatosis and fibrosis.^12,13

Xenobiotic and oxidant exposure affects the health of every cell and organ in the body. Accordingly, NAC has shown benefit in a wide range of conditions, from Bipolar disorder to Metabolic Syndrome, lung disease to infertility.² Every one living in our modern world could benefit from the improved antioxidant protection of NAC. 

References

1. Kampa M, Castanas E. Human health effects of air pollution. Environmental pollution. 2008 Jan 31;151(2):362-7.Available at https://www.researchgate.net/profile/Elias_Castanas/publication/6192687_'Human_Health_Effects_of_Air_Pollution'/links/00b7d52caecc424493000000.pdf
2. Pizzorno JE, Katzinger JJ. Glutathione: Physiological and clinical relevance. Journal of Restorative Medicine. 2012 Sep 1; 1(1):24-37.. Available at http://www.ingentaconnect.com/content/aarm/jrm/2012/00000001/00000001/art00003?crawler=true
3. Ji L, Liu R, Zhang XD, Chen HL, Bai H, Wang X, Zhao HL, Liang X, Hai CX. N-acetylcysteine attenuates phosgene-induced acute lung injury via up-regulation of Nrf2 expression. Inhalation toxicology. 2010 Jun 1; 22(7):535-42. Available at http://web.a.ebscohost.com.ezproxy.csu.edu.au/ehost/pdfviewer/pdfviewer?sid=9cc0d6b5-ae79-4930-9710-ba0f5b602659%40sessionmgr4006&vid=1&hid=4002
4. Lee JM, Li J, Johnson DA, Stein TD, Kraft AD, Calkins MJ, Jakel RJ, Johnson JA. Nrf2, a multi-organ protector?. The FASEB Journal. 2005 Jul 1; 19(9):1061-6. Available at https://www.researchgate.net/profile/Thor_Stein/publication/7757481_Nrf2_a_multi-organ_protector/links/546ab17d0cf2397f78301bd0.pdf
5. Luczak MW, Zhitkovich A. Role of direct reactivity with metals in chemoprotection by N-acetylcysteine against chromium (VI), cadmium (II), and cobalt (II). Free Radical Biology and Medicine. 2013 Dec 31; 65:262-9. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823631/
6. Kasperczyk S, Dobrakowski M, Kasperczyk A, Ostałowska A, Birkner E. The administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to lead. Clinical Toxicology. 2013 Jul 1;51 (6):480-6.Available at https://www.researchgate.net/profile/Stawomir_Kasperczyk/publication/237015640_The_administration_of_N-acetylcysteine_reduces_oxidative_stress_and_regulates_glutathione_metabolism_in_the_blood_cells_of_workers_exposed_to_lead/links/5601a69d08aed9851827c978.pdf
7. Kasperczyk S, Dobrakowski M, Kasperczyk A, Romuk E, Rykaczewska-Czerwińska M, Pawlas N, Birkner E. Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers. Toxicology and industrial health. 2015 Mar 2:0748233715571152. Available at https://www.researchgate.net/profile/Stawomir_Kasperczyk/publication/273153910_Effect_of_N-acetylcysteine_administration_on_homocysteine_level_oxidative_damage_to_proteins_and_levels_of_iron_(Fe)_and_Fe-related_proteins_in_lead-exposed_workers/links/5536a87c0cf2058efdea9105.pdf
8. Heard KJ. Acetylcysteine for acetaminophen poisoning. New England Journal of Medicine. 2008 Jul 17; 359(3):285-92. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637612/
9. Enjalbert F, Rapior S, Nouguier-Soulé J, Guillon S, Amouroux N, Cabot C. Treatment of amatoxin poisoning: 20-year retrospective analysis. Journal of Toxicology: Clinical Toxicology. 2002 Jan 1; 40(6):715-57. Available at https://www.researchgate.net/profile/Sylvie_Rapior/publication/10997296_Treatment_of_amatoxin_poisoning_20-year_retrospective_analysis/links/09e41502a01a682369000000.pdf
10. Lee WM, Hynan LS, Rossaro L, Fontana RJ, Stravitz RT, Larson AM, Davern TJ, Murray NG, McCashland T, Reisch JS, Robuck PR. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009 Sep 30;137(3):856-64. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189485/
11. Kortsalioudaki C, Taylor RM, Cheeseman P, Bansal S, Mieli‐Vergani G, Dhawan A. Safety and efficacy of N‐acetylcysteine in children with non‐acetaminophen‐induced acute liver failure. Liver transplantation. 2008 Jan 1;14 (1):25-30. Available at http://onlinelibrary.wiley.com/doi/10.1002/lt.21246/epdf
12. Manouchehr K, Akbar A, Koorosh M, MohammadK T, Sara F, Hosain B, Javad K, Maryam Z, Farzad N. N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease. Hepatitis monthly. 2010 Jan; 2010 (1, Winter):12-6. Available at http://hepatmon.com/?page=article&article_id=377
13. De Oliveira CP, Stefano JT, De Siqueira ER, Silva LS, de Campos Mazo DF, Lima VM, Furuya CK, Mello ES, Souza FG, Rabello F, Santos TE. Combination of N‐acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non‐alcoholic steatohepatitis. Hepatology Research. 2008 Feb 1;38(2):159-65. Available at https://www.researchgate.net/profile/JOSE_TADEU_Stefano/publication/229974532_Combination_of_Nacetylcysteine_and_metformin_improves_histological_steatosis_and_fibrosis_in_patients_with_nonalcoholic_steatohepatitis/links/5502d2000cf2d60c0e64923c.pdf