The benefits of NAC to human health

N-acetylcysteine (NAC) is a supplement form of the non-essential amino acid, cysteine and is associated with antioxidant capability, immune support, detoxification and much more. NAC has received a lot of positive attention recently, particularly in light of the pandemic and vaccination roll out, and in this week’s blog we explore some of the evidence in relation to this and also its wider application.

Cysteine is found in most high-protein foods, such as poultry, eggs, dairy, seeds, and legumes. Additionally, cruciferous vegetables such as cabbage, Brussels sprouts, broccoli, and kale, are rich sources of sulphur-containing compounds important in the production of cysteine.

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NAC was introduced in the 1960s as a mucolytic drug for chronic respiratory diseases to loosen thick mucus in the lungs and is used in hospital settings in patients with acute bronchopulmonary disease (pneumonia, bronchitis). It is also used to treat paracetamol toxicity.

While oral cysteine does not make it through the digestive tract, supplemental cysteine in the form of NAC is effective at raising blood and tissue levels. The N-acetyl group attached to cysteine aids its absorption and also protects from stomach acid.

Precursor to Glutathione 1-3

One of the most important biological functions attributed to NAC, and its prime value, is its ability to boost the production of the most powerful antioxidant in the human body – glutathione.

Glutathione is a tripeptide made from three amino acids: cysteine, glutamate, and glycine. Our cysteine levels therefore determine how much and how fast we make glutathione.

Glutathione is known as the “master antioxidant” because of its dominance throughout the body and its capacity to support and regenerate other antioxidants.

As an antioxidant, glutathione helps to combat free radicals, which are molecules that can damage body cells and tissues at molecular level. It also plays a significant role in detoxification and reducing inflammation. Its vital roles include:

  • boosting the immune system
  • detoxification of both xenobiotic and endogenous compounds
  • cofactor for several antioxidant enzymes
  • regeneration of vitamins C and E
  • neutralization of free radicals
  • regulation of cellular proliferation and apoptosis
  • support for mitochondrial function and maintenance of mitochondrial DNA.

So why are so many of us depleted? – Common threats to glutathione levels include ageing, medications, poor nutrition, toxins, sedentary lifestyle, infections, and stress. With approximately half of the population in England now taking medications regularly, many of us relying on processed foods, and heightened levels of chronic stress, it is no wonder that so many of us are in poor health. In fact, the depletion of glutathione has been associated with a range of illnesses and chronic diseases including neurodegenerative, pulmonary, liver, immune, and cardiovascular disease. Furthermore, its antioxidant capabilities have been shown to protect DNA, cells, tissues, and organs from damage, inflammation, and toxins. The significant role of sufficient glutathione to health has therefore become ever more evident.

Mechanism of Action in Immune Function 1-6

Perhaps of particular concern at the moment is the many ways in which NAC can boost immune function. These include:

  • Increasing glutathione concentrations in the blood
  • Having its own antioxidative properties to protect against cellular damage
  • Breaking disulphide bridges between macromolecules, disrupting platelet aggregation and breaking bonds between blood cells and clotting factor, maintaining fluidity of blood and oxygen flow
  • Contributing to a reduction in mucus viscosity
  • Exhibiting vasodilatory properties by increasing cyclic GMP levels and by contributing to the regeneration of endothelial-derived relaxing factor (a potent vasodilator)
  • Reducing the formation of proinflammatory cytokines, such as IL-9 and TNF-α
  • Restoring Natural Killer cells
  • Thinning mucus in the bronchial tubes and boosting glutathione levels – helping to decrease the severity and frequency of wheezing, coughing and respiratory attacks

COVID-19 and other Viral Infections 1-15

The anti-inflammatory effects of glutathione in viral infection are employed through:

  • the decrease of reactive oxygen species (ROS) production
  • reduction of NF-kB activation
  • inhibition of ACE activity

ROS – Perhaps of most importance is NAC’s ability to combat oxidative stress in the body. Oxidative stress is a nonspecific pathological condition reflecting an imbalance between the increased production of ROS and an inability of biological systems to detoxify the reactive intermediates or to repair the resulting damage.

Mounting evidence supports the concept that oxidative stress and associated inflammation contribute to the pathogenesis of various chronic diseases, which are now known to increase the risk of severe illness in COVID-19 patients.

Cellular immunity is necessary to fight viral infections and is regulated by an oxidant/antioxidant balance. In the immune cells of immune-compromised people, or the elderly, ROS is often increased due to decreased glutathione levels, which causes dysregulation of immune responses, particularly of T cell-mediated functions. This may explain the depressed cell-mediated immunity and increased mortality found in elderly persons as a result of infectious diseases, such as pneumonia.

Decreased levels of glutathione occurring in COVID-19 patients with chronic diseases could therefore be an initiating factor that moves redox homeostasis toward oxidative stress, and in doing so, exacerbates lung inflammation, leading to acute respiratory distress syndrome (ARDS), organ failure, and even death.

As ROS play a crucial role in inflammatory responses and viral replication, antioxidants such as NAC, that exert antiviral and anti-inflammatory effects, are suggested as candidates for the treatment of a cytokine storm induced by severe influenza.

Cytokine Storm – when we encounter an antigen, our body launches various immune responses, one of which is the release of proteins called cytokines. Cytokines communicate with the immune system and are key to controlling the growth and activity of other immune system cells. They therefore help and direct the body’s immune and inflammation responses.

Cytokine responses are, however, elevated more so than normal in some COVID-19 patients, inducing an exaggerated and inappropriate immune response, and thus too much inflammation. This ‘cytokine storm’ can cause damage to organs, particularly the lungs. The immune system can therefore be more damaging in this respect than the virus itself.

The oxidative stress environment created by a cytokine storm may be attenuated by NAC’s antioxidant effect. For example, NAC inhibited both H5N1 replication and H5N1-induced production of pro-inflammatory molecules (e.g., IL6, CCL5, CXCL8, and CXCL10) in lung epithelial cells.

Glutathione has also been shown to improve the life span of T-cells (white blood cells) which is crucial as they can become worn out and die because of a cytokine storm. Furthermore, NAC can help to mediate inflammatory pathways, lessening the damaging effects on the body.

NF-κB pathway support – RNA viruses need active NF-κB pathway support within host cells to replicate. For human coronaviruses, suppression of NF-κB significantly reduced the replication rate. NAC has demonstrated to inhibit NF-κB, as well as the replication of human influenza viruses in human lung epithelial cells.   In theory therefore, NAC has the potential to inhibit SARS-Cov-2 because of its ability to negatively regulate NF-κB.

ACE Activity – The inflammatory response can be traced back to the pathway of viral entry through its receptor, angiotensin-converting enzyme 2 (ACE2). ACE2 is a protease that, with its companion the angiotensin-converting enzyme (ACE), takes part in the renin-angiotensin system. ACE2 counters the activity of ACE. The downstream effects of the two enzymes are opposite: ACE activity leads to vasoconstriction, oxidative stress, inflammation, and apoptosis, whereas ACE2 causes vasodilatation, angiogenesis and anti-inflammatory, anti-oxidative and anti-apoptotic effects. Reducing the oxidative stress secondary to the imbalance between ACE and ACE2 could be the best approach for the prevention and treatment of COVID-19.

Main protease – In SARS-Cov-2, main protease (Mpro) is required for viral replication. Research suggested that NAC may bind to Cys-145, an active site of Mpro, which could potentially inhibit its protease activity and thus inhibit viral replication.

Although most research into NAC supplementation has taken place on a small scale, clinical trials of NAC use on patients with respiratory problems and other viral infections provide promising results.

Further Studies

In human studies, a randomised double-blind trial was conducted on a total of 262 elderly subjects who received 600 mg NAC twice daily, as opposed to those receiving placebo. The group that received NAC experienced fewer influenza-like symptoms and days of bed confinement.

Another 2020 review study found that 600 mg/day of NAC could serve as a preventive measure against COVID-19, particularly for those who are likely to have repeated exposures (such as health care workers).

Further studies have researched the anti-viral activity of NAC against influenza A strains. Both in vitro and in vivo experiments show that NAC enhances glutathione levels, which reduce viral load by inhibiting viral replication in a number of viruses e.g. influenza A (H3N2).

At higher doses (≥1200mg), NAC acts as an antioxidant through complex mechanisms, which can combat conditions of oxidative stress. Its antioxidant activity is also key for addressing numerous other conditions caused by oxidative stress, such as heart disease and pulmonary disease, all of which have been identified as increasing the severity of viral infection.

A Note on Vitamin D and Selenium 1-3

Vitamin D has received a lot of positive attention with regards to COVID-19 and there are several studies that have reported on glutathione levels positively correlating with active vitamin D. A recent experimental study showed that glutathione deficiency, and the associated oxidative stress, epigenetically alters vitamin D regulatory genes, and as a result, the suppressed gene expression decreases vitamin D biosynthesis, leading to a secondary deficiency of vitamin D. This study shows that glutathione is essential for the control of endogenous vitamin D biosynthesis and demonstrates potential benefits of glutathione treatment in reducing vitamin D deficiency and conditions associated with it.

Selenium – to operate as an antioxidant, glutathione requires a group of enzymes known as the glutathione peroxidases. These are selenoproteins, meaning they are selenium dependent. Glutathione peroxidases functionally link selenium and glutathione, which both show correlations with clinical outcomes in COVID-19. Given their linked biochemical roles, there are likely to be common factors and mechanisms underlying the therapeutic importance of selenium and glutathione in viral infections.
Low levels of selenium, which are present among the population, are hence another reason for low glutathione levels in the body. It can take two years, however, for selenium pools in the body to fill. This makes NAC a useful protective interim to ensure adequate production of glutathione, as its action is immediate, whereas selenium will be slow to build up and be active.

Vaccinations

Vaccines help our immune systems to identify and destroy specific pathogens before they have an opportunity to cause us serious illness. Our immune response to vaccines involves the production of antibodies, which attack the invading pathogen, along with memory cells, which remain in the body. This provides defence against the same or related pathogens, should you be exposed again.

Inflammation is a fundamental part of immune system activation. Our immune reaction should, however, be appropriate, without being unduly prolonged or excessively inflammatory.

Each of us will have an individualised response to the vaccination but supporting your immune system before receiving the vaccination may help your body to respond appropriately. Moreover, a healthy immune response produces more antibodies and the development of memory cells to safeguard against future assault, increasing the effectiveness of the vaccine.

If you have decided to have the COVID-19 vaccination, there are many ways of supporting your immune system pre- and post-vaccination. This can be beneficial for all, but particularly those who are elderly, or may suffer with a compromised immune system, whose reaction to the vaccination maybe inappropriate.

For the immune system to generate good protection against a disease following vaccination, it needs adequate nutrition and micronutrients. It is beneficial therefore to stay well-nourished, as well as hydrated, to rest, and to manage your stress levels, both before and after the vaccination.

In addition to this, NAC may help in several ways:

Supports detoxificationLiver – most glutathione is produced intracellularly in the liver. The liver is crucial to the body’s detoxification, and immune system function and is required to filter pollutants, drugs, and medications, including vaccines. It functions by changing the chemical structure of toxins, rendering them harmless and removing them from the bloodstream.

Kidneys – our kidneys filter toxins out of the blood into urine and are highly dependent on an adequate supply of glutathione to support normal function. The kidneys are also exposed to high concentrations of oxidants.

If these organs are functioning sub-optimally, toxins can build up and overwhelm our detoxification systems, affecting our immunity, and well-being. NAC supports the detoxification of the kidneys and liver.

Reducing inflammationthe antioxidant capacity of NAC can help protect immune cells from being damaged and lessen the ill-effects of inflammation. NAC can help to support a healthy inflammatory response both in preparation for the vaccine and afterwards. Inflammation is one of the main reasons you may feel discomfort after the vaccine.

Wider Indications

Gut Health

Low levels of glutathione can increase oxidative stress and oxidative stress and inflammation can further deplete glutathione. This vicious cycle will potentially affect gut barrier function contributing to a systemic inflammatory state with widespread symptoms.

Chronic Disease

Low levels of glutathione go hand-in-hand with oxidative stress and are virtually universal among patients with chronic disease.

Lung Disease 1-5

Alterations in alveolar and lung glutathione metabolism are widely recognised as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, ARDS, cystic fibrosis and asthma.

Oral use of NAC may be implicated in chronic lung conditions as not only does it contribute antioxidant benefits but is also used as a mucolytic agent, reducing mucous viscosity and mucociliary clearance. One study showed that 600 mg of NAC twice a day significantly improved lung function and symptoms in those with COPD and a 2015 meta-analysis evaluating 13 studies concluded that 1,200 milligrams of NAC per day reduced the incidence and severity of flares in people with COPD compared to a placebo. In a further meta-analysis, NAC promoted the symptom improvement rate of patients with acute exacerbation COPD, improved lung function and enhanced the body’s antioxidant capacity. 

Kidney Disease 1

The results of a recent meta-analysis and systematic review found that NAC can benefit kidney function, relieve inflammation, and reduce cardiovascular events among people with chronic kidney disease.

Inflammatory Conditions 1

Arthritis – NAC may improve inflammatory conditions, such as arthritis, due to its antioxidant properties. Antioxidants can help reduce inflammation and stabilise tissue around the joints, which may lessen some of the pain associated with it.

IBD – Preliminary evidence has shown NAC supplementation reduces inflammation, alleviates oxidative stress, and ameliorates tissue damage in the intestines. These benefits are believed to be achieved through NAC helping to maintain intracellular concentrations of glutathione.

Neuroprotective 1

Glutathione is one of few compounds that can cross the blood-brain barrier, which makes it extremely important in regard to neurological disorders. Many neurodegenerative and psychological conditions have been associated with inflammation, oxidative stress, mitochondrial dysfunction, toxicity, and compromised integrity at both the gastrointestinal tract and blood-brain barrier, all of which can be linked to glutathione depletion. Glutathione also helps to regulate glutamate, a neurotransmitter, important for memory and learning.

Anti-ageing

As we age, glutathione production gradually decreases. We can therefore become susceptible to symptoms associated with ageing such as reduced physical and cognitive function, vulnerability to infections, muscle, joint and bone pain, age spots and wrinkles, and chronic diseases. Increasing glutathione levels and supplementing with NAC can help protect against oxidative stress, slowing down ageing at a cellular level.

Environmental Pollutants

By increasing levels of glutathione and combating oxidative stress, NAC may help protect from many environmental toxins and pollutants.

How to Boost Glutathione Levels 1-3

There are a number of reasons why our body’s glutathione levels may become depleted but maintaining adequate levels of this important antioxidant is incredibly important for numerous reasons as outlined above and for our overall health in general.  Below are some of the ways in which we can help to increase our levels:

  • Consume sulphur rich foods – sulphur is an important mineral that occurs in the amino acid cysteine and is found in cruciferous vegetables. Garlic and onions also have sulphur-containing compounds. Several studies have shown that eating sulfur-rich foods may reduce oxidative stress by boosting glutathione levels.
  • Eat foods rich in vitamin C – studies have shown that vitamin C helps to combat free radicals, meaning there is more glutathione available for the body to use. Vitamin C also helps to reprocess glutathione back to its active form.
  • Increase your intake of selenium-rich foods.
  • Consume foods that naturally contain glutathione such as spinach, avocados, and asparagus.
  • Exercise regularly – this is helpful in maintaining or increasing antioxidant levels, especially glutathione.
  • Supplement with NAC. Oral glutathione has poor bioavailability because enzymes break glutathione down during ingestion – taking NAC is a way to overcome this problem.

Note: Since NAC can impact the platelets and reduce coagulation, it may be contraindicated if you have a bleeding disorder or are taking blood-thinning medications

Key Takeaways

  • NAC is a supplement form of the non-essential amino acid, cysteine and is associated with antioxidant capability, immune support, and detoxification.
  • The N-acetyl group attached to cysteine facilitates the absorption of cysteine and it also protects it from stomach acid.
  • One of the most important biological functions of NAC is its ability to boost the production of the most powerful antioxidant known to the body – glutathione.
  • Common threats to glutathione levels include ageing, medications, poor nutrition, environmental toxins, sedentary lifestyle, infection, and stress.
  • Decreased levels of glutathione occurring in COVID-19 patients with chronic diseases could be a triggering factor that shifts redox homeostasis toward oxidative stress, exacerbating lung inflammation and leading to ARDS and multiorgan failure.
  • Cellular immunity is required to fight viral infections, and these are regulated by an oxidant-antioxidant balance.
  • NAC has demonstrated to inhibit NF-κB, as well as the replication of human influenza viruses in human lung epithelial cells.
  • NAC may help to support your immune system pre- and post-vaccination.
  • NAC can benefit the brain as it has a role in numerous pathways
  • NAC can break down mucus and replenish glutathione in the lungs, which helps to reduce airway damage and breathing difficulties.
  • NAC may improve inflammatory conditions such as symptoms of arthritisdue to its antioxidant properties.
  • Naturally boost glutathione levels by consuming sulphur rich foods, eating foods rich in vitamin C and exercising.

If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.

helen@cytoplan.co.uk
01684 310099

Amanda Williams and the Cytoplan Editorial Team


References

Introduction

  1. Shi, Z. and Puyo, C. A. (2020) “N-Acetylcysteine to Combat COVID-19: An Evidence Review,” Therapeutics and Clinical Risk Management, 16, p. 1047. doi: 10.2147/TCRM.S273700.
  2. Pizzorno, J. (2014) “Glutathione!,” Integrative Medicine: A Clinician’s Journal, 13(1), p. 8. Available at: /pmc/articles/PMC4684116/ (Accessed: September 7, 2021).

Precursor to Glutathione

  1. Mokhtari, V., Afsharian, P., Shahhoseini, M., Kalantar, S. M., & Moini, A. (2017). A Review on Various Uses of N-Acetyl Cysteine. Cell Journal (Yakhteh), 19(1), 11. https://doi.org/10.22074/CELLJ.2016.4872
  2. Pizzorno, J. (2014) “Glutathione!,” Integrative Medicine: A Clinician’s Journal, 13(1), p. 8. Available at: /pmc/articles/PMC4684116/ (Accessed: September 7, 2021).
  3. Health Survey for England – 2013 – NHS Digital (2014). Available at: https://digital.nhs.uk/data-and-information/publications/statistical/health-survey-for-england/health-survey-for-england-2013 (Accessed: September 14, 2021).

Mechanism of Action in Immune Function

  1. Droge, W. and Breitkreutz, R. (2000) ‘Glutathione and immune function’, Proceedings of the Nutrition Society. CAB International, 59(4), pp. 595–600. doi: 10.1017/S0029665100000847.
  2. Sanguinetti, C. M. (2016) ‘N-acetylcysteine in COPD: Why, how, and when?’, Multidisciplinary Respiratory Medicine. BioMed Central Ltd. doi: 10.1186/s40248-016-0039-2.
  3. Cazzola, M. et al. (2015) ‘Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: A meta-analysis’, European Respiratory Review. European Respiratory Society, pp. 451–461. doi: 10.1183/16000617.00002215.
  4. Stey, C. et al. (2000) ‘The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review’, European Respiratory Journal. European Respiratory Society, 16(2), pp. 253–262.
  5. Immunomodulatory and protective effects of N-acetylcysteine in mitogen-activated murine splenocytes in vitro,” Toxicology, 116(1–3), pp. 219–226. doi: 10.1016/S0300-483X(96)03520-2.
  6. N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19 – The Centre for Evidence-Based Medicine (no date). Available at: https://www.cebm.net/covid-19/n-acetylcysteine-a-rapid-review-of-the-evidence-for-effectiveness-in-treating-covid-19/ (Accessed: September 10, 2021).

COVID-19 and other Viral Infections 

  1. DJ, B. (2000) “What is oxidative stress?,” Metabolism: clinical and experimental, 49(2 Suppl 1), pp. 3–8. doi: 10.1016/S0026-0495(00)80077-3.
  2. Polonikov, A. (2020) “Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients,” ACS Infectious Diseases, 6(7), pp. 1558–1562. doi: 10.1021/ACSINFECDIS.0C00288.
  3. Silvagno, F., Vernone, A., & Pescarmona, G. P. (2020). The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19. Antioxidants, 9(7), 1–16. https://doi.org/10.3390/ANTIOX9070624
  4. Shi, Z. and Puyo, C. A. (2020) “N-Acetylcysteine to Combat COVID-19: An Evidence Review,” Therapeutics and Clinical Risk Management, 16, p. 1047. doi: 10.2147/TCRM.S273700.
  5. Poppe, M. et al. (2017) “The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells,” PLoS Pathogens, 13(3). doi: 10.1371/JOURNAL.PPAT.1006286.
  6. J, G. et al. (2010) “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,” Biochemical pharmacology, 79(3), pp. 413–420. doi: 10.1016/J.BCP.2009.08.025.
  7. S, D. F., C, G. and L, C. (1997) “Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment,” The European respiratory journal, 10(7), pp. 1535–1541. doi: 10.1183/09031936.97.10071535.
  8. N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19 – The Centre for Evidence-Based Medicine (no date). Available at: https://www.cebm.net/covid-19/n-acetylcysteine-a-rapid-review-of-the-evidence-for-effectiveness-in-treating-covid-19/ (Accessed: September 10, 2021).
  9. De Quay, B., Malinverni, R. and Lauterburg, B. H. (1992) ‘Glutathione depletion in HIV-infected patients: Role of cysteine deficiency and effect of oral N-acetylcysteine’, AIDS, 6(8), pp. 815–819. doi: 10.1097/00002030-199208000-00008.
  10. Geiler, J. et al. (2010) ‘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’, Biochemical Pharmacology, 79(3), pp. 413–420. doi: 10.1016/j.bcp.2009.08.025.
  11. Cao, M. et al. (2020) ‘Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China’, medRxiv. Cold Spring Harbor Laboratory Press, p. 2020.03.04.20030395. doi: 10.1101/2020.03.04.20030395.
  12. Ghezzi, P. and Ungheri, D. (2004) ‘Synergistic combination of n-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model’, International Journal of Immunopathology and Pharmacology. Biomedical Research Press s.a.s., 17(1), pp. 99–102. doi: 10.1177/039463200401700114.
  13. Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW 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; 79: 413–420
  14. IFM (2020). The Functional Medicine Approach to COVID-19: Virus-Specific Nutraceutical and Botanical Agents [online]. Available at: https://www.ifm.org/news-insights/the-functional-medicine-approach-to-covid-19-virus-specific-nutraceutical-and-botanical-agents/Accessed 12th May 2020.
  15. Jorge-Aarón, R.-M. and Rosa-Ester, M.-P. (2020) “N-acetylcysteine as a potential treatment for novel coronavirus disease 2019,” Future Microbiology, 15(11), pp. 959–962. doi: 10.2217/FMB-2020-0074. 

A Note on Vitamin D and Selenium

  1. Polonikov, A. (2020) “Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients,” ACS Infectious Diseases, 6(7), pp. 1558–1562. doi: 10.1021/ACSINFECDIS.0C00288.
  2. Parsanathan, R., & Jain, S. K. (2019). Glutathione deficiency induces epigenetic alterations of vitamin D metabolism genes in the livers of high-fat diet-fed obese mice. Scientific Reports 2019 9:1, 9(1), 1–11. https://doi.org/10.1038/s41598-019-51377-5
  3. Taylor, E. W. and Radding, W. (2020) “Understanding Selenium and Glutathione as Antiviral Factors in COVID-19: Does the Viral Mpro Protease Target Host Selenoproteins and Glutathione Synthesis?,” Frontiers in Nutrition, 0, p. 143. doi: 10.3389/FNUT.2020.00143.

Lung Disease

  1. I, R. and W, M. (2000) “Oxidative stress and regulation of glutathione in lung inflammation,” The European respiratory journal, 16(3), pp. 534–554. doi: 10.1034/J.1399-3003.2000.016003534.X.
  2. Sanguinetti, C. M. (2016) ‘N-acetylcysteine in COPD: Why, how, and when?’, Multidisciplinary Respiratory Medicine. BioMed Central Ltd. doi: 10.1186/s40248-016-0039-2.
  3. Cazzola, M. et al. (2015) ‘Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: A meta-analysis’, European Respiratory Review. European Respiratory Society, pp. 451–461. doi: 10.1183/16000617.00002215.
  4. Stey, C. et al. (2000) ‘The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review’, European Respiratory Journal. European Respiratory Society, 16(2), pp. 253–262.
  5. C, J. et al. (2021) “Systematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease,” Annals of palliative medicine, 10(6), pp. 6564–6576. doi: 10.21037/APM-21-1138.

Kidney Disease

  1. Jun, M., Venkataraman, V., Razavian, M., Cooper, B., Zoungas, S., Ninomiya, T., Webster, A. C., & Perkovic, V. (2012). Antioxidants for chronic kidney disease. Cochrane Database of Systematic Reviews, 2012(10). https://doi.org/10.1002/14651858.CD008176.PUB2

Inflammatory Conditions

  1. et al. (2015) “N-acetylcysteine and intestinal health: a focus on its mechanism of action,” Frontiers in bioscience (Landmark edition), 20(5), pp. 872–891. doi: 10.2741/4342.

Neuroprotective

  1. CD, P., KR, H. and A, P. (2013) “Antioxidants as potential therapeutics for neuropsychiatric disorders,” Progress in neuro-psychopharmacology & biological psychiatry, 46, pp. 214–223. doi: 10.1016/J.PNPBP.2012.10.017.

How to Naturally Boost Glutathione Levels

  1. JJ, B., H, V., MI, W., G, van P., & PJ, van B. (1994). Consumption of Brussels sprouts results in elevated alpha-class glutathione S-transferase levels in human blood plasma. Carcinogenesis, 15(5), 1073–1075. https://doi.org/10.1093/CARCIN/15.5.1073
  2. Z, B., P, M., F, H., M, H., S, H.-N., & F, A. (2011). Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial. European Journal of Clinical Nutrition, 65(8), 972–977. https://doi.org/10.1038/EJCN.2011.59
  3. KJ, L. et al. (2003) “Vitamin C augments lymphocyte glutathione in subjects with ascorbate deficiency,” The American journal of clinical nutrition, 77(1), pp. 189–195. doi: 10.1093/AJCN/77.1.189.

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11 thoughts on “The benefits of NAC to human health

  1. Impressive, beautifully written, I’ve been using it for 10 years for a chronic liver problem and have recommended it to various colleagues and friends particularly for respiratory problems. Now I’ll just forward this article

  2. Fascinating article thank you! I started taking NAC at the start of the pandemic and will continue to do so at 2 capsules daily. What is the safe upper dose please and are there any contraindications?

    1. Hi Bev – NAC is safe at quite high doses but it is important always to evaluate the person taking and the appropriateness and safety in that person. For this reason I am not keen to give a dose level. Acutely doses of 500-1500mg are usually recommended with a reduced dose for long term supplementation. It is contra indicated in pregnancy, renal disease and some other conditions, most particularly bleeding disorders. It is important to realise anything that is bioactive will have indications and contraindications and not many supplements are panaceas to be taken without due consideration. But I do acknowledge that NAC has received much press cover recently as to how it can help with many Covid-related symptoms and side-effects – so I understand why so many more people are now taking it. But always good to be aware that if you are taking anything over the long term it is good to have it assessed for you by a health professional or nutritional therapist. Thanks, Amanda

  3. Really informative and very timely article as I was looking for advice to manage mucosity and inflammation alongside asthma. Easy to read and understand and appreciate the summary points at the end.

  4. This is the most useful information I have read in a long time. My daughter had been on NAC to support a detoxification program to remove heavy metals from her tissues and I was aware of the link with breaking down clots but I had no idea about its role with glutathione. She has been suffering brain fog since coming off anti-depressants in February and I think we will try a course of NAC and see if that improves. Thank you.

  5. Very helpful and informative article. The first that I have read which gives helpful advice before taking the Covid vaccination. I am very grateful that you have made this information available.

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