The challenges of the COVID-19 pandemic have forced an intensified period of research over the last couple of years, with numerous compounds being investigated for their anti-inflammatory and immuno-modulatory effects. One such compound that has received attention is N-Acetyl-L-Cysteine (NAC), a relatively unknown semi-essential amino acid which has been showing some good results in the management of respiratory conditions and immune health. Many may not be aware of the importance of NAC, but one of its key functions in the body is to make the master antioxidant glutathione, arguably the most important antioxidant in the body and an essential nutrient for fighting cellular damage and optimizing immune health.

Mechanism of action

NAC helps to relieve symptoms by reducing inflammation and loosening mucous in the respiratory airways, thereby improving overall lung function. By thinning mucous and boosting glutathione levels, NAC may help to decrease the severity and frequency of wheezing, coughing and respiratory attacks in a number of conditions, and may be particularly useful in the elderly due to the fact that plasma cysteine and glutathione levels tend to decline with increasing age.

Chronic respiratory conditions

Because of its key role in the body, research on N-Acetyl-L-Cysteine has focused on a variety of therapeutic areas, not least among them respiratory health. Due to both its antioxidant and expectorant capabilities, NAC has been successfully investigated in patients suffering with a range of chronic respiratory conditions including COPD (chronic obstructive pulmonary disease)1-4, chronic bronchitis5-7, cystic fibrosis, asthma, pulmonary fibrosis and allergies8. Whilst several studies have demonstrated that NAC can reduce the rate of exacerbations in patients with later-stage COPD, a paper published in September 2020 showed a dose-dependent effect for NAC in early-stage COPD, suggesting that an increased dose might lead to improved outcomes when given at an earlier stage.9

Acute respiratory conditions

NAC has also shown promise in the treatment of more acute conditions and infections such as influenza and pneumonia, particularly in the elderly. In a 6-month placebo-controlled clinical study, elderly subjects receiving 600mg NAC daily experienced significantly fewer influenza-like episodes and days in bed than did the placebo group. In addition, significantly fewer of the NAC group developed symptoms despite the rate of infection between both groups being the same.10

In another study, 1200mg NAC daily helped to reduce oxidative stress and its associated inflammatory lung damage in patients with community-acquired pneumonia, a condition most often caused by bacterial or viral infection.11

A review of the data published in December 2020, concluded that NAC may indeed help improve outcomes in people with acute respiratory distress syndrome (ARDS) and acute lung injury following viral infection.12

Cytokine storm

We now know that at the heart of most severe cases of illness and death from COVID-19, is a dysregulated host immune response following infection with the virus, and much of the research has been centred around ameliorating the so-called “cytokine storm”. A cytokine storm is an extreme inflammatory response that can lead to acute respiratory distress, organ failure, and death. Research suggests that NAC among other compounds may help to reduce the inflammation in the lungs from RNA viruses and boost type 1 interferon response, thereby improving the body’s ability to create antibodies against these viruses. The researchers conclude that these compounds may indeed, “help provide relief to people infected with encapsulated RNA viruses such as influenza and coronavirus.”13

1. Pirabbasi E, Shahar S et al. Efficacy of Ascorbic Acid (Vitamin C) and/N-Acetylcysteine (NAC) Supplementation on nutritional and Antioxidant Status of Male Chronic Obstructive Disease (COPD) Patients. J Nutri Sci Vitaminol (Tokyo) 2016;62(1):54-61
2. PNR Dekhuijzen and WJC van Beurden. The role for N-acetylcysteine in the management of COPD. Int J Chron Obstruct Pulmon Dis. 2006 Jun; 1(2):99-106
3. Yanfei Shen, Wanru Cai, Shu Lei & Zhongheng Zhang. Effect of High/Low Dose N-Acetylcysteine on Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis. COPD: J Chron Obstruct Pulmon Dis. vol 11 2014 Issue 3:351-358
4. Claudio M Sanguinetti. N-acetylcysteine in COPD: why, how, and when? Multidiscip Respir Med. 2016; 11:8
5. Grandjean EM, Berthet P et al. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther. 2000 Feb;22(2):209-21
6. Reichenberger F, Tamm M. N-acetylcystein in the therapy of chronic bronchitis. Pneumologies. 2002 Dec;56(12):793-7
7. C Stey, J Steurer et al. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. European Respiratory Journal 2000 16:253-262
8. Tirouvanziam R, Conrad CK, Bottiglieri T et al. High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci USA. 2006 Mar 21; 103(12):4628-4633
9. Tian H, Zhou Y, Tang L et al. High-dose N-acetylcysteine for long-term, regular treatment of early-stage chronic obstructive pulmonary disease (GOLD I-II): study protocol for a multicenter, double-blinded, parallel-group, randomized controlled trial in China(2020) 21:780.
10. 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 Respir J. 1997 Jul;10(7):1535-41
11. Quianwen Zhang, Yuanrong Ju et al. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia. Medicine (Baltimore). 2018 Nov;97(45):e13087
12. Schloss J, Leach M, Brown D et al. The effects of N-acetyl cysteine on acute viral respiratory infections in humans: A rapid review2020 Dec; 7(4): 232–239
13. DiNicolantonio JJ & McCarty MF. Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus. Progress in Cardiovascular Diseases. Available online 12 February 2020.

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