Optimal Sinus and Respiratory Health with N-Acetyl-L-Cysteine (NAC)

A vast and growing body of published medical research is pointing to the benefits of inhaled or intranasal NAC for the entire respiratory tract, from the upper (nose, sinuses, throat) to the lower (lungs).

Written by: Dr. Brian Weeks and Dr. Ashley Sikand, ENT Surgeons

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What is N-Acetyl-L-Cysteine (NAC)?

N-acetyl-L-cysteine (NAC) is a derivative of cysteine, a naturally occurring amino acid that is found in many foods and is synthesized by the human body. NAC has long been familiar to supplement users, primarily because it is a precursor to the body’s master antioxidant, glutathione. 1,2 But now, scientific research suggests a wide range of respiratory benefits for NAC when used as a sinus/nasal rinse or irrigation system.

WHAT YOU NEED TO KNOW

A vast and growing body of published medical research is pointing to the benefits of inhaled or intranasal NAC for the entire respiratory tract, from the upper (nose, sinuses, throat) to the lower (lungs). NAC works with a powerful six-way action:

  1. it reduces thick and excessive mucus
  2. it calms harmful inflammation
  3. it acts as an anti-infective agent for both bacteria and viruses
  4. it prevents development of dangerous biofilms
  5. it upregulates glutathione, the body’s master antioxidant
  6. it helps to maintain and restore the natural immune system within the respiratory tract

The Mucus Conundrum

Nobody likes to talk about mucus, but it’s actually not a bad thing. In fact, you could say that a healthy respiratory tract “runs” on mucus. By this we mean it relies on a thin, moving layer of mucus to protect the airway, remove unwanted particles (think dust, infection, pollutants, pollen) and provide lubrication in order for the underlying mucous membrane to function properly.

When mucus runs wild

Many conditions, including allergies, viral infections, bacterial sinus and lung diseases, can result in inflammation that causes the mucus system to become dysfunctional. Mucus becomes excessive, changes in character and color, and becomes sticky and dense. Symptoms can include congestion, nasal blockage, cough and difficulty in breathing.

NAC to the rescue!
N-acetyl-L-cysteine has been used by physicians since the 1960s to help remove excess mucus and infected secretions from the sinuses, windpipe and lungs. Studies show that it has a mucolytic action, thinning out thick mucus so it can be more easily removed from sinus passages and the respiratory tract.3,4 NAC helps to prevent crusting of mucus, and it also helps to restore the health of the mucous membrane lining of the respiratory tract.

Disrupts Dangerous Biofilms

In addition to thinning and clearing mucus, NAC also works to disrupt bacterial biofilms. Biofilms are sticky “slime layers” that are secreted by bacteria to help them adhere to any surface and to protect them from the immune system and antibiotics. If you’ve ever wondered why your teeth are filmy in the morning – even though you brushed them right before bedtime – that’s the result of fast-growing biofilms being produced by more than 500 types of bacteria in your mouth. If you don’t remove oral biofilms by regular brushing, they will continue to grow, hardening into plaque that can lead to tooth decay and gingivitis.

Biofilms are also found in the lungs, where they are involved in many respiratory infections, including ventilator-associated pneumonia, bronchitis and chronic obstructive pulmonary disease (COPD). You may not be able to “brush” your lungs, but NAC may be able to help. Many in vitro studies have demonstrated that NAC is effective in inhibiting biofilm formation, disrupting preformed biofilms (both initial and mature), and reducing bacterial viability in biofilms. These properties are currently being studied in human clinical trials on NAC, either alone or in combination with antibiotics.5

Fights Inflammation

The science of N-acetyl-L-cysteine has shown it to be a powerful anti-inflammatory agent. NAC calms down the inflammatory response by stopping the action of chemicals (cytokines and chemokines) produced in the nose, sinuses and lungs that cause inflammation and cell damage. Whether from allergies, infection or immune problems – NAC helps to limit inflammation, which can help reduce swelling, congestion, mucus production and irritation.6,7,8

A good example of NAC’s inflammation fighting properties can be seen in fibrosis, which is a type of scarring in the lungs caused by pro-inflammatory chemicals secreted by the body. Fibrosis scarring interferes with proper lung function. Laboratory studies have shown that N-acetyl-L-cysteine may help protect against fibrosis by limiting the production of the inflammatory compounds that initiate it.9,10,11

A Powerful Antioxidant

NAC has a well-established antioxidant effect. In addition, it is a critical building block for the body’s synthesis of the master antioxidant glutathione. Found in every cell in the body, glutathione combats the destructive free radical-mediated oxidative damage that is associated with most age-related chronic diseases.12,13

The glutathione-enhancing action of N-acetyl-L-cysteine is important for restoring the health of damaged cells and tissue. In fact, NAC is used by physicians to treat drug overdoses (acetaminophen) because of its potent effect in detoxifying the injured liver, preventing further oxidative stress, and restoring normal glutathione levels. For this reason, N-acetyl-L-cysteine is included in the World Health Organization Model List of Essential Medicines14,15,16

Respiratory Benefits

Oxidative stress and inflammation are often found together in respiratory conditions, contributing to their symptoms and development. In emphysema, for example, oxidative stress in the lungs evokes an inflammatory response, which constricts the airways and allows fluid and excess mucus to build in the lungs. The ultimate result is tissue damage, often irreversible. By a combination of its antioxidant and anti-inflammatory action, N-acetyl-L-cysteine can help limit the damage while also thinning and clearing the excess mucus to ease breathing.

In patients with chronic obstructive pulmonary disease (COPD), NAC has been associated with fewer incidences of flare-ups (exacerbations) and fewer days in hospital.17,18,19,20

N-acetyl-L-cysteine is also being studied in acute respiratory distress syndrome (ARDS). This is a very serious inflammatory condition of the lungs – particularly in instances of pneumonia and critical lung infections – in which fluid fills the lungs, leaving little if any room for life-giving oxygen. Patients with ARDS must often be placed on mechanical ventilators, which results in high mortality rates. After having shown promise in animal studies,21,22 several human studies have demonstrated significant improvement of symptoms with oral NAC, with clinical improvements and shorter ICU stays.23,24,25

NAC has also shown promise in the treatment of chronic bronchitis. This is a lingering condition marked by inflammation in the lungs and airways, and characterized by chest discomfort, wheezing, coughing up mucus, or a dry “smoker’s cough”. Several human studies have shown that oral NAC could reduce exacerbations and significantly improves symptoms.26,27

Protection against Infection

Numerous studies on the actions of NAC also indicate that it can have anti-infective action against a variety of harmful bacteria, viruses and even fungi. By thinning out the mucus layer, NAC makes it harder for harmful pathogens to adhere to the cells lining the respiratory tract. This effect has been demonstrated in multiple laboratory experiments.28,29,30 One study of particular interest was on respiratory syncytial virus (RSV). This is a particularly nasty and rapid-growing virus that attaches tenaciously to the cells lining the airways, causing damage to their structure of the airways. N-acetyl-L-cysteine was shown in the laboratory to prevent RSV-related cell damage and assist in cell recovery.31

NAC (N-acetyl-L-cysteine) has also been demonstrated to have biological actions against various viral strains that cause influenza (‘flu). According to a study published in a respected medical journal32, NAC stopped viruses from reproducing in cells infected with the H5N1 influenza virus (“avian flu”) under laboratory conditions. NAC also prevented inflammation in the respiratory tract caused by this virus. The authors concluded that N-acetyl-L-cysteine may be a potential treatment in the case of viral pandemics.

The deadliest pandemic in recorded history was the 1918 H1N1 “Spanish flu”, which, according to the Centers for Disease Control and Prevention, killed an estimated 50 million people worldwide.33 In an important study on H1N1 conducted in Italy on H1N1-positive patients, only 25% of those receiving NAC treatment developed symptoms versus 79% of patients not treated with NAC.34

In regard to COVID-19, global research efforts are continuing. Much attention in the scientific and medical communities has been given to a major study conducted at the University of North Carolina.35 Researchers there made a breakthrough discovery, finding that the SARS-CoV-2 virus that causes COVID-19 first infects the nasal cavity, from which it can spread to the throat and ultimately to the lungs, with potentially serious or fatal consequences.

In a university news release, the UNC study co-author Dr. Richard Boucher outlined the importance of clearing viruses from the area in which they first attach to cause disease, saying “If the nose is the dominant initial site from which lung infections are seeded, then the widespread use of masks to protect the nasal passages, as well as any therapeutic strategies that reduce virus in the nose, such as nasal irrigation or antiviral nasal sprays, could be beneficial.”36 The use of nose sprays and nasal rinses to protect against viral infections like COVID-19 was given a comprehensive review recently in the journal of the American Academy of Otolaryngology-Head and Neck Surgery. Conclusions stated that intranasal delivery represents an important area of research for COVID-19 and other viral diseases.37

Delivering NAC

Although NAC is often taken in pill form, it is now thought that many of its benefits for the respiratory system could be better gained by delivering it directly to where it is needed; the mucous membrane that lines the nose, sinuses, trachea, and the bronchi that feed into the lungs.
Intranasal or inhaled NAC therapy is not new. For decades, it has been administered by doctors and hospitals directly by mist, solution, nebulizer, even by IV. The safety of N-acetyl-L-cysteine is unquestioned, even at high doses.38

Disclaimer:
This site contains information that is of a general nature regarding NAC. We do not advertise or recommend any products for any specific uses. Consult your clinician if you are interested in learning more about the benefits of NAC

References:

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2 Sansone RA, Sansone LA. Getting a Knack for NAC: N-Acetyl-Cysteine. Innov Clin Neurosci. 2011 Jan;8(1):10-4.

3 Available at: https://www.webmd.com/lung/mucus-in-chest-overview#1. Accessed January 3, 2021.

4 Kalyuzhin OV. Effect of N-acetylcysteine on mucosal immunity of respiratory tract. Ter Arkh. 2018 Apr 19;90(3):89-95.

5 Blasi F, Page C, Rossolini GM, et al. The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections. Respir Med. 2016 Aug;117:190-7.

6 Santus P, Corsico A, Solidoro P, et al. Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine. COPD. 2014 Dec;11(6):705-17.

7 Aldini G, Altomare A, Baron G, et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res. 2018 Jul;52(7):751-62.

8 Zhang Q., Ju Y., Ma Y., Wang T. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: A randomized controlled trial. Medicine (Baltimore). 2018;97(45)

9 Cu A, Ye Q, Sarria R, et al. N-acetylcysteine inhibits TNF-alpha, sTNFR, and TGF-beta1 release by alveolar macrophages in idiopathic pulmonary fibrosis in vitro. Sarcoidosis Vasc Diffuse Lung Dis. 2009 Jul;26(2):147-54.

10 Gosset P, Wallaert B, Tonnel AB, et al. Thiol regulation of the production of TNF-alpha, IL-6 and IL-8 by human alveolar macrophages. Eur Respir J. 1999 Jul;14(1):98-105.

11 Pinar Karapinar S, Ulum YZ, Ozcelik B, et al. The effect of N-acetylcysteine and calcium hydroxide on TNF-alpha and TGF-beta1 in lipopolysaccharide-activated macrophages. Arch Oral Biol. 2016 Aug;68:48-54.

12 Available at: https://www.sciencedirect.com/topics/neuroscience/glutathione . Accessed October 2, 2020.

13 Aldini G, Altomare A, Baron G, et al. op. cit.

14 Heard KJ. Acetylcysteine for acetaminophen poisoning. N Engl J Med. 2008 July 359(3): 285-292.

15 Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen- induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther. 1973;187:211–7.

16 Available at https://apps.who.int/iris/rest/bitstreams/1237479/retrieve. Accessed January 9, 2021.

17 Pela R, Calcagni AM, Subiaco S, et al. N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD. Respiration. 1999 Nov-Dec;66(6):495-500.

18 Poole PJ, Black PN. Preventing exacerbations of chronic bronchitis and COPD: therapeutic potential of mucolytic agents. Am J Respir Med. 2003;2(5):367-70.

19 Tse HN, Raiteri L, Wong KY, et al. High-dose N-acetylcysteine in stable COPD: the 1-year, double-blind, randomized, placebo-controlled HIACE study. Chest. 2013 Jul;144(1):106-18.

20 Tse HN, Raiteri L, Wong KY, et al. ibid.

21 Kao SJ, Wang D, Lin HI, et al. N-acetylcysteine abrogates acute lung injury induced by endotoxin. Clin Exp Pharmacol Physiol. 2006 Jan-Feb;33(1-2):33-40.

22 Su CF, Kao SJ, Chen HI. Acute respiratory distress syndrome and lung injury: Pathogenetic mechanism and therapeutic implication. World J Crit Care Med. 2012 Apr 4;1(2):50-60.

23 Available at: https://www.webmd.com/lung/mucus-in-chest-overview#1. Accessed January 09, 2021.

24 Walsh TS, Lee A. N-acetylcysteine administration in the critically ill. Intensive Care Med. 1999 May;25(5):432-4.

25 Bernard GR, Wheeler AP, Arons MM, et al. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest. 1997 Jul;112(1):164-72.

26 Cazzola M, Calzetta L, Page C, et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015 Sep;24(137):451-61.

27 Wei J, Pang CS, Han J, et al. Effect of Orally Administered N-Acetylcysteine on Chronic Bronchitis: A Meta-analysis. Adv Ther. 2019 Dec;36(12):3356-67.

28 Zheng CH, Ahmed K, Rikitomi N, et al. The effects of S-carboxymethylcysteine and N-acetylcysteine on the adherence of Moraxella catarrhalis to human pharyngeal epithelial cells. Microbiol Immunol. 1999;43(2):107-13.

29 Riise GC, Qvarfordt I, Larsson S, et al. Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro. Respiration. 2000;67(5):552-8.

30 Kalyuzhin OV. Effect of N-acetylcysteine on mucosal immunity of respiratory tract. Ter Arkh. 2018 Apr 19;90(3):89-95.

31 Mata M, Sarrion I, Armengot M, et al. Respiratory syncytial virus inhibits ciliagenesis in differentiated normal human bronchial epithelial cells: effectiveness of N-acetylcysteine. PLoS One. 2012;7(10):e48037.

32 Geiler J, Michaelis M, Naczk P, et al. N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A. virus. Biochem. Pharmacol. 2010 Feb 1;79(3):413-20.

33 Available at https://www.cdc.gov/flu/pandemic-resources/reconstruction-1918-virus.html. Accessed January 9, 2021.

34 De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Resp J. 1997 Jul;10(7):1535-41.

35 Hou YJ, Okuda K, Edwards CE, et al. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell 2020 Jul 23;182(2):429-446.

36 Available at https://news.unchealthcare.org/2020/06/researchers-map-sars-cov-2-infection-in-cells-of-nasal-cavity-bronchia-lungs/. Accessed January 3, 2021.

37 Higgins TS, WU AW, et al. Intranasal antiviral drug delivery and coronavirus disease (COVID-19): A state of the art review. Otolaryngol Head Neck Surg. 2020 Oct;163(4):682-694.

38 Calverley P, Rogliani P, Papi A. Safety of N-acetylcysteine at high doses in chronic respiratory diseases: A review. Drug Saf. 2020 Dec 16 doi: 10.1007/s40264-020-01026-y. Online ahead of print.