I briefly touched on N-Acetylcysteine in my article about Glycine, but I kept finding more interesting data and even did a little experiment on myself. Let me share the most interesting and practical use-cases of NAC that I’ve found.

This article is not health or medical advice. Please contact your physician before trying anything described in this article.

1, What is N-Acetylcysteine?

N-Acetylcysteine, often called NAC, is a powerful tool for fighting oxidative stress in the body. It serves as a precursor to Glutathione, the most potent antioxidant in the body.

Glutathione is a tripeptide consisting of cysteine, glycine, and glutamic acid, found in surprisingly high levels in most cells. It acts as the master antioxidant of the cell, recycling other antioxidants such as Vitamin C and E, detoxifying heavy metals and other harmful substances, and supporting immune function.

Produced in our cells, glutathione offers numerous benefits, including reducing oxidative stress, improving insulin resistance, supporting brain health, and promoting longevity. The formation of glutathione requires both cysteine (from NAC) and glycine.

For further reading about Glutathione, I recommend this excellent article [6]

2, N-Acetylcysteine for anti-aging

Ok, this was covered mostly in my Glycine article, because GlyNAC study [3] made some waves and many people started taking combination of Glycine and N-Acetylcysteine as anti-aging intervention.

I do take it as well, in this precise mix:

• Glycine: 5g
• Collagen peptides: 15g
• Vitamine C: 250mg (to aid Collagen absorption)
• N-Acetylcysteine: 500mg
• All mixed in water, with NAC taken as pill

And indeed, the main mechanism is raising body levels of Glutathione, the most potent antioxidant in the human body, aiding in detoxification, boosting the immune system, and promoting cellular repair. Additionally, it has been shown that centenarians have statistically higher levels of Glutathione [5].

Complete list of benefits and even some videos can be seen in my Glycine article, and I encourage you to read it as well.

3, N-Acetylcysteine as mucolytic

N-Acetylcysteine (NAC) is a mucolytic agent that has been used for over 50 years to treat various respiratory conditions.

As a mucolytic, NAC works by breaking disulfide bonds in the mucus, reducing its viscosity and making it easier to clear from the airways. This action is particularly helpful for individuals with conditions such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, and bronchiectasis, where excessive mucus production can lead to breathing difficulties and recurrent infections.

Overall, the dual actions of NAC as a mucolytic and antioxidant make it a valuable treatment option for individuals with respiratory conditions characterized by excessive mucus production and inflammation.

This paper from 2018 explain the mucolytic mechanisms of NAC [12], and they even have nice illustration explaining the effect:

4, N-Acetylcysteine for flu prevention

Ok, this part is really interesting, as I personally tested it on myself with good effect. But don’t just take my word for it; listen to what Dr. Andrew Huberman has to say.

Andrew speaks about both the mucolytic effect and flu prevention in this short video:

The study he mentions is NAC against flu study [1] and the dose from the study was 2x600mg/day long-term (for 6 months). The results were quite remarkable, as the group on NAC experienced an 80% reduction in flu compared to the group without NAC.

The dose Andrew used was 600 to 900mg, 3 times per day.

The dose I used was 6x500mg per day (for 3 days in a row, then gradually tapering down to the normal daily dose of 500mg as part of the GlyNAC protocol).

Update: Right now, my wife is down with the Wuhan Flu, as well as one of my kids. It’s been one week, and I am still going strong, with NAC as my secret weapon (not so secret, as my wife is taking it as well now to aid in the recovery).

5, N-Acetylcysteine as cure for mushroom poisoning

It was quite a surprise for me to find out that N-Acetylcysteine is used as one of the treatments for Death Cap poisoning. Death Cap, Amanita Phalloides, is the most deadly mushroom in Europe and North America; only 30 grams are estimated to kill an adult human.

I was just thinking about what to do if I poisoned myself and came up with this protocol:

Call an ambulance, vomit like you’ve never vomited before to expel everything, then drink lots of water and induce more vomiting. After that, take charcoal and NAC, pray, and wait for the ambulance.

You can also check this article [7] to find out other treatments you might receive with NAC in the hospital as cure for mushroom poisoning!

6, N-Acetylcysteine as Atherosclerosis cure

There is a study from 2023 [2] showing multiple possible mechanisms by which NAC attenuates the development and progression of Atherosclerosis. Those mechanisms mentioned in study are:

• modifications of lipid metabolism
• inhibition of the expressions of gelatinase, MMP-2, and MMP-9
• blocking the in vivo biotransformation of native LDL to ox-LDL, and directly suppressing ROS production from ox-LDL
• increasing intracellular glutathione levels, and thus protecting endothelial function
• attenuation of NF-κB and p38-MAPK signaling, thus decreasing inflammatory cytokine production
• the preservation of circulating endothelial cell progenitor cells
• reduction of homocysteine levels
• attenuation of endothelial senescence and damage, while enhancing endothelial function through multiple mechanisms, including activation of Akt signaling and eNOS
• the preservation of M2 polarization in the hyperlipidemic condition, thus reducing inflammation and oxidative stress

7, N-Acetylcysteine as tromb solvant

There are also several studies showing trombolytic effect of NAC. I recommend checking at least this one [8]

The mechanism is that N-acetylcysteine reduces the disulfide bonds of the von Willebrand Factor multimers that maintain platelets linked in arterial thrombi, thereby inducing thrombus dissolution.

8, N-Acetylcysteine and Wuhan Flu

There is growing body of evidence shoving N-Acetylcysteine’s positive role on both COVID-19 prevention and treatment. This study demonstrates the effect of Glutathione for prevention of COVID-19 immunothrombosis [9]

Study from 2022 [10] focuses on both the prevention and treatment of COVID-19 through NAC supplementation and even describes potential treatment mechanisms. What is applicable for you is the conclusion of using at least 1200mg of NAC per day when you become ill with COVID-19. This information is also perfectly in line with Dr. Andrew Huberman’s claims from chapter 4 about flu prevention and further confirms the powerful efficacy of NAC.

There is also meta-analysis from 2023 [11] exploring the effects of NAC on the severity and mortality of COVID-19 patients. I included this study here as it indeed describes the same effect as the previous study, but it also provides a great illustration of the process during the progression of COVID-19.

9, Risks of taking N-Acetylcysteine

I haven’t found much negative effects of NAC, but this article would be incomplete without mentioning them.

There has been a study in flies [3] showing an actual decrease in lifespan in the group given NAC; however, keep in mind that flies are much simpler organisms, and often even studies on mice (mammal) do not translate well to humans. In my opinion, it’s worth looking at the GlyNAC study [4] as well, where a combination of Glycine and N-Acetylcysteine was given to humans.

Additional side effects and risks may partially serve as further confirmation that N-Acetylcysteine is functioning as intended:

• Gastrointestinal issues: Some people may experience stomach discomfort, nausea, vomiting, or diarrhea after taking NAC. This might be caused by the acidity of NAC, so I would try to offset that by consuming something alkaline with it. (Thanks @izzers_tennis for experimenting with it!)
• Allergic reactions: Although rare, some individuals might experience an allergic reaction to NAC, which can manifest as a rash, itching, or difficulty breathing.
• Low blood pressure: In some cases, NAC may cause a drop in blood pressure, leading to dizziness or lightheadedness. While this may be beneficial for individuals with higher blood pressure, it’s important to monitor its effects closely.
• Headache: A small percentage of users might experience headaches after taking NAC.
• Interactions with medications: NAC may interact with certain medications, such as nitroglycerin, and can increase their effects.

This article is by no means exhaustive, as NAC might also help with brain health, mental disorders, fertility and more. However, I do believe it is valuable piece about N-Acetylcysteine, as it puts anti-aging properties into more broad context.

I cite a lot of studies in this article, but after looking at statistics from my Glycine article, only 2% of visitors actually click any study links. I strongly encourage you not to stop reading here, but pick one or two studies that sound most interesting to you and actually look at them, at least briefly!

References

[1] NAC against flu study

Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment, S De Flora, C Grassi, L Carati, European Respiratory Journal Jul 1997, 10 (7) 1535-1541; DOI: 10.1183/09031936.97.10071535

[2] N-Acetylcysteine and Atherosclerosis: Promises and Challenges

Cui, Y.; Zhu, Q.; Hao, H.; Flaker, G.C.; Liu, Z. N-Acetylcysteine and Atherosclerosis: Promises and Challenges. Antioxidants 2023, 12, 2073. https://doi.org/10.3390/antiox12122073

[3] GlyNAC study

Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):75-89. doi: 10.1093/gerona/glac135. PMID: 35975308; PMCID: PMC9879756.

[4] NAC effect on insect lifespan

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.

[5] Glutathione statistically higher in centenarians

Xu, Q., Wu, C., Zhu, Q. et al. Metagenomic and metabolomic remodeling in nonagenarians and centenarians and its association with genetic and socioeconomic factors. Nat Aging 2, 438–452 (2022)

[6] Glutathione!

Pizzorno J. Glutathione! Integr Med (Encinitas). 2014 Feb;13(1):8-12. PMID: 26770075; PMCID: PMC4684116.

[7] Death Cap Wikipedia

Wikipedia contributors. (2024, January 26). Amanita phalloides. In Wikipedia, The Free Encyclopedia. Retrieved 09:45, January 31, 2024, from https://en.wikipedia.org/w/index.php?title=Amanita_phalloides&oldid=1199364955

[8] NAC trombolityc effect

Martinez de Lizarrondo S, Gakuba C, Herbig BA, Repessé Y, Ali C, Denis CV, Lenting PJ, Touzé E, Diamond SL, Vivien D, Gauberti M. Potent Thrombolytic Effect of N-Acetylcysteine on Arterial Thrombi. Circulation. 2017 Aug 15;136(7):646-660. doi: 10.1161/CIRCULATIONAHA.117.027290. Epub 2017 May 9. PMID: 28487393; PMCID: PMC5560034.

[9] Glutathione for prevention of COVID19 imunotrombosis

Ira Glassman, Nghia Le, Mercedeh Mirhosseini, Cheldon Ann Alcantara, Aamna Asif, Anabel Goulding, Shafi Muneer, Manpreet Singh, Jeremiah Robison, Frederick Guilford, Vishwanath Venketaraman. The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review. Front. Biosci. (Landmark Ed) 2023, 28(3), 59.

[10] N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions

Izquierdo-Alonso JL, Pérez-Rial S, Rivera CG, Peces-Barba G. N-acetylcysteine for prevention and treatment of COVID-19: Current state of evidence and future directions. J Infect Public Health. 2022 Dec;15(12):1477-1483. doi: 10.1016/j.jiph.2022.11.009. Epub 2022 Nov 12. PMID: 36410267; PMCID: PMC9651994.

[11] N-acetylcysteine reduces severity and mortality in COVID-19 patients: A systematic review and meta-analysis

Alam MS, Hasan MN, Maowa Z, Khatun F, Nazir KHMNH, Alam MZ. N-acetylcysteine reduces severity and mortality in COVID-19 patients: A systematic review and meta-analysis. J Adv Vet Anim Res. 2023 Jun 30;10(2):157-168. doi: 10.5455/javar.2023.j665. PMID: 37534078; PMCID: PMC10390689.

[12] Mucolytic effect of NAC explained

Giancarlo Aldini, Alessandra Altomare, Giovanna Baron, Giulio Vistoli, Marina Carini, Luisa Borsani & Francesco Sergio (2018) N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why, Free Radical Research, 52:7, 751-762, DOI: 10.1080/10715762.2018.1468564

[13] 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

Janina Geiler, Martin Michaelis, Patrizia Naczk, Anke Leutz, Klaus Langer, Hans-Wilhelm Doerr, Jindrich Cinatl,
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,
Volume 79, Issue 3,
2010,
Pages 413-420,
ISSN 0006-2952,
https://doi.org/10.1016/j.bcp.2009.08.025.

[14] N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia

Zhang, Qianwen MSa,b; Ju, Yuanrong MSa; Ma, Yan MSa; Wang, Tao MSc,∗. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: A randomized controlled trial. Medicine 97(45):p e13087, November 2018. | DOI: 10.1097/MD.0000000000013087

[15] N-acetylcysteine attenuates systemic platelet activation and cerebral vessel thrombosis in diabetes

Bin Wang, Tak Yee Aw, Karen Y. Stokes,
N-acetylcysteine attenuates systemic platelet activation and cerebral vessel thrombosis in diabetes,
Redox Biology,
Volume 14,
2018,
Pages 218-228,
ISSN 2213-2317,
https://doi.org/10.1016/j.redox.2017.09.005.
(https://www.sciencedirect.com/science/article/pii/S2213231717306286)

[16] N-acetylcysteine inhibits thrombosis in a murine model of myeloproliferative neoplasm

Brianna M. Craver, Gajalakshmi Ramanathan, Summer Hoang, Xinyue Chang, Laura F. Mendez Luque, Stefan Brooks, Hew Yeng Lai, Angela G. Fleischman; N-acetylcysteine inhibits thrombosis in a murine model of myeloproliferative neoplasm. Blood Adv 2020; 4 (2): 312–321. doi: https://doi.org/10.1182/bloodadvances.2019000967

[17] In Vitro Study of N-acetylcysteine on Coagulation Factors in Plasma Samples from Healthy Subjects

Jang, D.H., Weaver, M.D. & Pizon, A.F. In Vitro Study of N-acetylcysteine on Coagulation Factors in Plasma Samples from Healthy Subjects. J. Med. Toxicol. 9, 49–53 (2013). https://doi.org/10.1007/s13181-012-0242-2

N-Acetylcysteine and 9 things you should know by cancel-aging