N-Acetylcysteine (NAC) is a potent antioxidant and a derivative of the amino acid cysteine. It is the subject of scientific research going back 50 years and is used as a therapeutic agent for various medical conditions. NAC is a precursor to glutathione, a key molecule in cellular antioxidant defense, and it also has mucolytic properties, correspondingly making it useful in the treatment of respiratory conditions. In this article, we will explore what NAC is, how it is synthesized, its historical discovery, the research surrounding its potential health benefits and risks, and the potential health outcomes from its consumption.

What is N-Acetylcysteine?

N-Acetylcysteine (NAC) is an amino acid derivative of cysteine. It is a precursor to glutathione, an important antioxidant and detoxifying molecule in the body. NAC is available in supplement form and is also used as a prescription medication for several medical conditions.

How is N-Acetylcysteine synthesized?

N-Acetylcysteine is synthesized by acetylating the thiol group of cysteine, which is an amino acid that contains a sulfur atom. The acetylation reaction involves adding an acetyl group (-COCH3) to the thiol group (-SH) of cysteine, which creates N-Acetylcysteine. Producers carry out this process using chemical synthesis or through enzymatic reactions.

Historical discovery of N-Acetylcysteine

N-Acetylcysteine was first used in the 1960s as a mucolytic agent to treat respiratory conditions such as bronchitis and cystic fibrosis. Since then, the compound has been extensively studied and has been found to have a wide range of therapeutic effects.

In the 1980s, researchers discovered NAC to be a potent antioxidant and a precursor to glutathione. This discovery led to further research on the compound’s potential use in preventing and treating oxidative stress-related diseases such as Parkinson’s disease, Alzheimer’s disease, and cancer.

Research surrounding N-Acetylcysteine

N-Acetylcysteine has been extensively studied for its potential health benefits and risks. We discuss some of the most significant research findings below:

N-Acetylcysteine as an antioxidant

N-Acetylcysteine is a potent antioxidant, shown to protect against oxidative stress in various cell and animal models. One study shows that NAC reduces oxidative stress and improves mitochondrial function in the liver (1). Another study in mice finds that NAC supplementation reduces oxidative stress and inflammation in the brain (2). These findings suggest that NAC may have a protective effect against oxidative stress-related diseases.

N-Acetylcysteine and respiratory conditions

N-Acetylcysteine is commonly used as a mucolytic agent to treat respiratory conditions such as bronchitis and cystic fibrosis. It works by breaking down the disulfide bonds in mucoproteins, which helps to reduce the viscosity of mucus and improve its clearance from the respiratory tract. A systematic review of 49 NAC related studies shows that NAC reduces the number of exacerbations and improves lung function in patients with chronic obstructive pulmonary disease (COPD) (3). Another study finds that NAC reduces the risk of exacerbations in patients with cystic fibrosis (4).

N-Acetylcysteine and liver health

N-Acetylcysteine has protective effects on the liver by increasing glutathione levels and reducing oxidative stress. NAC improves liver function and reduces inflammation in patients with non-alcoholic fatty liver disease (5). Moreover, NAC’s therapeutic effects reduce liver damage and improve liver function in patients with alcoholic liver disease (6).

N-Acetylcysteine and mental health

N-Acetylcysteine has been studied for its potential use in treating various mental health conditions, including addiction, depression, and obsessive-compulsive disorder (OCD). A study conducted in patients with cocaine addiction finds that NAC reduces craving and relapse rates (7). Another study in patients with major depressive disorder finds that NAC improves symptoms of depression (8). A systematic review of 18 studies also shows that NAC may be effective in reducing symptoms of OCD (9).

N-Acetylcysteine and cancer

N-Acetylcysteine has been studied for its potential use in preventing and treating cancer. NAC may reduce the risk of lung cancer in smokers (10), however, other studies have found conflicting results, and more research is needed to determine the potential role of NAC in cancer prevention and treatment.

Risks and side effects of N-Acetylcysteine

While N-Acetylcysteine is generally considered safe when used in appropriate doses, there are some potential side effects and risks associated with its use. Some of the most common side effects include nausea, vomiting, and diarrhea. These side effects are typically mild and resolve on their own.

There have been some reports of more serious side effects, such as allergic reactions and anaphylaxis, particularly in individuals with a history of asthma or allergies. In rare cases, excessively high doses of NAC can lead to liver toxicity, particularly in individuals with pre-existing liver disease.

NAC may also interact with certain medications, including nitroglycerin, which is used to treat angina, and certain chemotherapy drugs. Therefore, individuals taking these medications should consult with their healthcare provider before using NAC.

Potential health outcomes from N-Acetylcysteine consumption

While N-Acetylcysteine has been studied extensively for its potential health benefits, there are also some speculated health outcomes associated with its consumption. One of the most significant speculated benefits is its potential use in extending lifespan and delaying the aging process. Some studies show that NAC supplementation can increase lifespan in various animal models (11). Researchers must conduct additional work to determine whether these findings translate to humans.

Another potential benefit of N-Acetylcysteine is its use in improving exercise performance and reducing muscle fatigue. Some studies show that NAC supplementation can improve exercise performance and reduce fatigue in athletes (12). However, other studies have found conflicting results, and more research is needed to determine the potential role of NAC in exercise performance.

Conclusion

N-Acetylcysteine (NAC) is a potent antioxidant and a derivative of the amino acid cysteine. It has been extensively studied for its potential health benefits and has been found to have therapeutic effects in various medical conditions, including respiratory conditions, liver disease, mental health conditions, and cancer. While NAC is generally considered safe when used in appropriate doses, there are some potential side effects and risks associated with its use. However, the speculated health outcomes associated with NAC consumption, such as extending lifespan and improving exercise performance, require further research to confirm. As always, individuals should consult with their healthcare provider before using any supplements or medications.

References:

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2. Cuzzocrea S., Mazzon E., Costantino G., Serraino I., Dugo L., Calabrò G., Cucinotta G., De Sarro A., Caputi A.P. Beneficial effects of n-acetylcysteine on ischaemic brain injury. Br. J. Pharmacol. 2000;130:1219–1226. doi: 10.1038/sj.bjp.0703421. https://pubmed.ncbi.nlm.nih.gov/10903958/ 
3. Huang C, Kuo S, Lin L, Yang Y. The efficacy of N-acetylcysteine in chronic obstructive pulmonary disease patients: a meta-analysis. Ther Adv Respir Dis. 2023 Jan-Dec;17:17534666231158563. doi: 10.1177/17534666231158563. PMID: 36927162; PMCID: PMC10026096. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026096/ 
4. C. Conrad, J. Lymp, V. Thompson. (2015). Long-term treatment with oral N-acetylcysteine: Affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial Journal of Cystic Fibrosis, VOLUME 14, ISSUE 2, P219-227.  https://www.cysticfibrosisjournal.com/article/S1569-1993(14)00208-2/fulltext 
5. Khoshbaten M, Aliasgarzadeh A, Masnadi K, Tarzamani MK, Farhang S, Babaei H, Kiani J, Zaare M, Najafipoor F. N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease. Hepat Mon. 2010 Winter;10(1):12-6. Epub 2010 Mar 1. PMID: 22308119; PMCID: PMC3270338. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270338/ 
6. Morgan TR. Treatment of Alcoholic Liver Disease. Gastroenterol Hepatol (N Y). 2017 Jul;13(7):425-427. PMID: 28867971; PMCID: PMC5572973. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572973/ 
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8. Andrade C. N-Acetylcysteine Augmentation for Patients With Major Depressive Disorder and Bipolar Depression. J Clin Psychiatry. 2021 Feb 18;82(1):21f13891. doi: 10.4088/JCP.21f13891. PMID: 33999540. https://pubmed.ncbi.nlm.nih.gov/33999540/ 
9. Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, Sarris J. N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review. Clin Psychopharmacol Neurosci. 2015 Apr 30;13(1):12-24. doi: 10.9758/cpn.2015.13.1.12. PMID: 25912534; PMCID: PMC4423164. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423164/ 
10. Breau M, Houssaini A, Lipskaia L, Abid S, Born E, Marcos E, Czibik G, Attwe A, Beaulieu D, Palazzo A, Flaman JM, Bourachot B, Collin G, Tran Van Nhieu J, Bernard D, Mechta-Grigoriou F, Adnot S. The antioxidant N-acetylcysteine protects from lung emphysema but induces lung adenocarcinoma in mice. JCI Insight. 2019 Oct 3;4(19):e127647. doi: 10.1172/jci.insight.127647. PMID: 31578304; PMCID: PMC6795405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795405/ 
11. Shaposhnikov MV, Zemskaya NV, Koval LA, Schegoleva EV, Zhavoronkov A , Moskalev AA. Effects of N-acetyl-L-cysteine on lifespan, locomotor activity and stress-resistance of 3 Drosophila species with different lifespans. Aging (Albany NY). 2018 Sep 20;10(9):2428-2458. doi: 10.18632/aging.101561. PMID: 30243020; PMCID: PMC6188487. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188487/ 
12. de Jesus Pires de Moraes A, Andreato LV, Branco BHM, da Silva EL, Gonçalves MA, Dos Santos RZ, Becker AM, da Silveira Cavalcante L, da Silva Casagrande F, Benetti M. Effects of N-acetylcysteine supplementation on cellular damage and oxidative stress indicators in volleyball athletes. J Exerc Rehabil. 2018 Oct 31;14(5):802-809. doi: 10.12965/jer.1836152.076. PMID: 30443526; PMCID: PMC6222163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222163/