The Wholesome Journal

Supplementation of NAC and its Therapeutic Potential for Women and Men

Showing promise as an adjunctive treatment for multiple health conditions, N-acetylcysteine (NAC) performs a broad array of actions that may alleviate issues ranging from respiratory to neurological.

NAC is an acetylated form of the amino acid L-cysteine, which is involved in the synthesis of glutathione (GSH), a powerful antioxidant that exhibits numerous functions to protect cells against damage and toxicity. [1] As a nutritional supplement, NAC has been used for several decades as a mucolytic agent (having the ability to dissolve thick mucus) and in the treatment of acetaminophen poisoning. [2] More recently, it has been highlighted for its antioxidant and anti-inflammatory properties to help treat conditions where oxidative stress (OS), is involved. [3]

The following briefly describes NAC’s main mechanisms of action and the conditions/diseases that may benefit from its supplementation. Multiple studies and reviews have reported that NAC is generally well-tolerated and safe to use (within appropriate dosages) without any considerable side effects. [4, 2, 3, 5]

Remember to talk with your primary care doctor before starting any supplements, especially if taking other medications.

Mucolytic properties

The sulfhydryl groups that are part of NAC’s structure breaks down specific proteins in mucus, making it less viscous/thick. [3, 6] NAC also acts as an expectorant to help clear out the mucus from lung airways. [3]

This mucolytic action has been shown to relieve symptoms of several conditions including cystic fibrosis, contrast-induced nephropathy, chronic obstructive pulmonary disease (COPD) and other chronic respiratory illnesses. [7, 8]

NAC’s mucolytic property has also been shown to retract the negative effect of clomiphene citrate (CC) on the cervical mucus of women suffering from CC-resistant PCOS, thus potentially creating a more fertile environment for conception. [4]

Anti-inflammatory and antioxidant properties

Anti-inflammatory: NAC has been shown to inhibit pathways that lead to inflammation and reduce the synthesis of inflammatory markers such as cytokines. [2, 7]

Antioxidant: NAC also has the ability to act directly and indirectly as an antioxidant.

Direct antioxidant: NAC directly scavenges for free radicals and certain reactive oxidative species (ROS), compounds that cause oxidative stress, inflammation and cell damage. [4]

Indirect antioxidant: as stated above, NAC is a precursor to GSH. Excessive OS can deplete the body’s antioxidant capacity and reduce cysteine’s availability – limited cysteine decreases the rate of GSH synthesis and lessens the cell’s protection against damage. [9, 5] NAC can rapidly deliver cysteine to cells in an exclusive form, replenishing GSH levels and restoring redox imbalance. [7]

These protective properties of NAC have been shown to positively affect multiple conditions.

Liver disorders:

A systematic review reported that 69 studies found both OS and inflammation to be common occurrences in the development of liver damage and diseases. [1] Thus therapeutic approaches would involve protecting the liver’s cell components against oxidative injury – a major role of antioxidants. [1] This review showed overall good results for NAC’s role in attenuating both OS and inflammation in the liver. [1]

In addition to protecting cells against oxidative injury, NAC can (1) bind with metal ions and excrete them from the body, and (2) inhibit xenobiotic transformations. [3, 2] This promotes liver detoxification and may prevent heavy metal toxicity. [3]

Psychiatric disorders:

Further, OS and reduced antioxidant status are common in psychiatric disorders (schizophrenia, mood disorders, etc.) and neurodegenerative diseases (particularly related to aging). [7, 11] NAC has the capability to cross the blood-brain barrier (BBB) to deliver cysteine to the brain for utilization in the synthesis of and to increase levels of GSH. [7] It’s been shown that the single supplementation of either GSH or cysteine did not have the same effect of recovering/increasing GSH levels in the brain. [7]

A research review looked at findings from other systematic reviews and meta-analyses of NAC’s effect on psychiatric conditions and concluded that promising evidence supports its use as an adjunctive therapy. [7]


In addition to its mucolytic action, NAC has shown to relieve COPD exacerbations. [9] GSH is concentrated in the epithelial lining fluid and protects the integrity of the lung’s airspace, but these protective effects are decreased with excessive OS. [5, 8] NAC can help lessen the chronic inflammation in the lung’s airways, improving its function. [5, 8]

Regulates glutamate in the brain

The dysregulation of glutamate (a neurotransmitter) plays a crucial role in the development of various psychiatric conditions – particularly substance abuse, addiction and obsessive-compulsive disorder (OCD). [7, 10] NAC can activate the systems that ultimately increase glutamate levels. [10] Clinical trials show promise for NAC to be a valuable component in these psychiatric therapies. [11]

Other conditions that can benefit from NAC

NAC was also shown to have insulin-sensitizing properties, thus may support individuals with hyperinsulinemia and women with PCOS. [4]

Through several other actions, NAC shows promise in benefiting heart conditions including atherosclerosis progression in individuals with hypertension and hypercholesterolemia [9] and having an anti-carcinogenic / anti-mutagenic effect on certain types of cancers. [2]



[1] Queiroz de Andrade, K., Moura, F. A., Marques dos Santos, J., Pimentel de Araujo, O. R., Celia de Farias Santos, J., & Fonseca Goulart, M. O. (2015). Oxidative stress and inflammation in hepatic diseases: Therapeutic possibilities of n-acetylcysteine. International Journal of Molecular Sciences, 16(12), 30269-30308. DOI: 10.3390/ijms161226225

[2] Pei, Y., Liu, H., Yang, Y., Jiao, Y., Tay, F. R., & Chen, J. (2018). Biological activities and potential oral applications of n-acetylcysteine: Progress and prospects. Oxidative Medicine and Cellular Longevity, 1-14. DOI: 10.1155/2018/2835787

[3] Thorne Research, Inc. (2000). N-acetylcysteine. Alternative Medicine Review, 5(5), 467-471.

[4] Mokhtari, V., Afsharian, P., Shahhoseini, M., Kalantar, S. M., & Moini, A. (2017). A review on various uses of n-acetyl cysteine. Cell Journal, 19(1), 11-17. DOI: 10.22074/cellj.2016.4872

[5] Tse, H. N., & Steven Tseng, C. Z. (2014). Update on the pathological processes, molecular biology, and clinical utility of n-acetylcysteine in chronic obstructive pulmonary disease. International Journal of Chronic Obstructive Pulmonary Disease, 9, 825-836. DOI: 10.2147/COPD.S51057

[6] Aldini, G., Altomare, A., Baron, G., Vistoli, G., Carini, M., Borsani, L., & Sergio, F. (2018). N-acetylcysteine as an antioxidant and disulphide breaking agent: The reasons why. Free Radical Research, 52(7), 751-762. DOI:

[7] Ooi, S., Green, R., & Pak, S. (2018). N-acetylcysteine for the treatment of psychiatric disorders: A review of current evidence. BioMed Research International, 1-8. DOI: 10.1155/2018/2469486

[8] 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. DOI: 10.3109/15412555.2014.898040

[9] Shahripour, R. B., Harrigan, M. R., & Alexandrov, A. V. (2014). N-acetylcysteine (NAC) in neurological disorders: Mechanisms of action and therapeutic opportunities. Brain and Behavior, 4(2), 108-122. DOI: 10.1002/brb3.208

[10] McClure, E. A., Gipson, C. D., Malcolm, R. J., Kalivas, P. W., & Gray, K. M. (2014). Potential role of n-acetylcysteine in the management of substance use disorders. CNS Drugs, 28(2), 95-106. DOI: 10.1007/s40263-014-0142-x

[11] Tardiolo, G., Bramanti, P., & Mazzon, E. (2018). Overview on the effects of n-acetylcysteine in neurodegenerative diseases. Molecules, 23(12), 1-20. DOI: 10.3390/molecules23123305

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