N-acetylcysteine (NAC) is a nutritional compound that seems beneficial for mental health and everything in between. Or at least that’s how the initial research presented. Let’s look into how it might help you.
NAC, as it’s usually known, is a popular over-the-counter supplement and FDA-approved drug used for paracetamol overdose.[1] Interest in NAC’s use spans multiple conditions such as polycystic ovarian syndrome (PCOS) to respiratory illnesses such as COPD[2] and non-alcoholic fatty liver disease.[3]
I’ve seen some great results clinically using NAC within this variety of conditions. Still, in this article, I want to focus on the role that it can play in some mental health conditions such as depression, anxiety and addiction—one area in particular where I’ve seen some good results with patients.
We’ll cover some positive and negative research and ideas about how NAC can help you.
NAC is an amino acid and has multiple actions in the body.
Some of these actions include antioxidant effects, anti-inflammatory effects[4], reversal of energy production problems within cells[5] (referred to as mitochondrial dysfunction) and early research on regulating dopamine release in the brain.[6]
One of NAC’s main actions is as a component of glutathione, the “master antioxidant” of the body. Glutathione is also the primary antioxidant in the brain.[7] For some, NAC can be a rate-limiting factor for glutathione production. This limitation means that without NAC, a massive channel of detoxification in the liver called glutathione conjugation (see the connection) can’t work as well.[8] From here, people can experience a glutathione deficiency.
To put this in a more realistic context, this glutathione conjugation channel of the liver is responsible for breaking down inflammatory chemicals, alcohol, paracetamol, mould and bacteria toxins and some heavy metals such as cadmium, mercury and lead.[9]
I often joke to my local patients that this is the “Hong Kong” column of toxins.
Other things can cause a loss of glutathione too. For instance, high-fat diets, LDL cholesterol, linoleic acid from flaxseed oil and iron can all cause glutathione loss.[10]
For these reasons, NAC can step in to ensure that glutathione levels stay optimal in the body.
I’ve heard the term “antioxidant” a lot; why is it so important, and what’s oxidation?
Oxidation is essential when examining NAC’s role in mental health and the brain. I like to think of oxidation as a natural process in the body that causes damage when it gets out of control.
When oxidation isn’t managed well in the body, it can cause stress on the cells causing them to react and create issues.
It’s here where you might have heard the term “oxidative stress.”
Now, whilst it’s not a hugely discussed element in public health, I can guarantee you that if you spend thirty seconds in a naturopathic conference, someone will mention it.
As much as I joke about it, oxidative stress is essential when it comes to research into the development of disease. For example, one review has oxidative stress’s role in almost everything. From cancer, inflammation, seizure, Alzheimer’s disease, Parkinson’s disease, liver disease, heart attack, stroke and diabetes.[11] [12]
So taking a lot of antioxidants sounds like the right idea?
Well, current research suggests that in some cases, high supplementation with antioxidants may not be as beneficial as once thought. In fact, in some cases, they can interfere with vital processes that assist with exercise recovery and performance, for example.[13]
Therefore it’s better to give the body the resources it needs to manage “oxidation” in its own way.
Enter NAC and its ability to bring balance to glutathione production naturally without overdoing it.
The big question, though, is how does this translate to helping you feel better?
Enough about the more general uses of NAC. How does this translate to some of the different expressions of mental health you’re trying to manage?
Currently, NAC carries interest in its potential role in schizophrenia, bipolar disorder, depressive disorders, anxiety, OCD, substance use and addiction and chronic pain.[14]
Let’s look at depression first.
It’s an interesting time to write this article after a somewhat divisive study was released last week around low serotonin and a chemical imbalance not being a primary cause of depression.[15]
I’m going to write a more comprehensive article exploring what now. Still, an interesting question regarding this article is how some research points to SSRIs being anti-inflammatory, especially regarding neuroinflammation or inflammation in the brain.[16]
How do SSRIs being anti-inflammatory relate to NAC?
Glad you asked.
Remember we discussed oxidation a little earlier? Well, the brains of people with depression have seen higher levels of oxidative damage and increased levels of antioxidants that reduce after antidepressant therapy.
Based on this, NAC’s role in increasing glutathione, remember the preferred antioxidant of the brain, might have more importance than ever. In fact, studies are now looking at whether or not NAC may be a viable add-on to antidepressants for treatment-resistant depression.[17]
Other human studies have shown that NAC did not help with depression as a singular therapy, and if there have been successful studies, the effect has been modest but significant.[18] This subtle change suggests that NAC might be best with other agents, and I’d be inclined to agree from how I’ve used it in depression in the clinic.
NAC and anxiety conditions
At the writing of this article, we are still in the same place as some of the other conditions and how NAC can help. Most brains of people living with anxiety in its various forms have evidence of oxidative stress and changes in brain chemistry that make the use of NAC appropriate.
However, while preclinical and preliminary studies show scope for using NAC in anxiety,[19] it’s fair to say that human trials are necessary to see if we are still on the right track.
Which mental conditions does NAC help?
Remember, this article is specifically on mental health, and in this final section, I’m here to deliver some more promising news on where NAC might be able to help. First off, addiction.
Small studies have seen positive results for cannabis addiction,[20] cocaine dependency, traumatic brain injury, gambling and self-harm.[21]
NAC might help conditions associated with impulse control, rumination and negative thoughts that are difficult to control.[22]
It’s in this way where I see it help in the clinic. In fact, I wrote this whole article to get to this point because I see NAC work so well for these types of symptoms.
We can all identify with either our own experience or a close someone’s experience with negative, difficult-to-control thoughts.
These thoughts can be daily, hourly and unexpected. They don’t have to be related to addiction but can just get to the point where they just seem normal. A lot of the time, they can drive depressive and anxious feelings and acting out when it comes to eating and drug use.
Imagine turning the volume down on those thoughts and feeling as if they are less intense and more manageable than before.
It’s here where I’ve seen many people land almost immediately when using NAC in more acute doses than we see in some of the studies I’ve referenced above.
NAC can be used in these higher doses only temporarily. I would say a maximum of six months. However, from clinical experience, not research studies, so not medical advice, I see a lot of the benefits people experience from using NAC regarding their thought patterns stabilise over that time, to a point where the NAC isn’t as necessary.
Add counselling to NAC use for repetitive and negative thought patterns, and amplify the benefits.
Remember, this may not be the case for you, but I’ve seen this consistently in the clinic and will take this opportunity to recommend counselling to you if you are yet to try it for some of your less desirable thought patterns.
The state of the research relating to NAC and mental health is exciting, but it isn’t translating to human studies for every mental health condition.
For example, Sarris et al. found that NAC had no benefit for people with OCD.[23] Studies like these give a reality check to some of the excitement. Personally, I think they are just as important as the successful ones. The reason why? NAC is a good example of a situation where the hype of function-oriented science may not translate to singular forms of therapy on which you can rely. I think CBD might also be an excellent example of this, but I’ll leave the controversy out.
I hope this article shows that sometimes making common symptoms such as repetitive thinking, negative self-talk and impulse control less intense can ultimately lead to better outcomes regardless of the more condition-specific studies.
Now, this isn’t the case all the time. We still need to listen to studies that don’t tell us what we want to hear, and expectations need to realign. However, with NAC, I’m looking forward to seeing the broader potential it can play in the tool kit for people’s daily mental quality of life.
Hope this helps xx
References
[1] Yip L, Dart RC. A 20-hour treatment for acute acetaminophen overdose. N Engl J Med. 2003;348(24):2471-2472. doi:10.1056/NEJM200306123482422
[2] Calverley P, Rogliani P, Papi A. Safety of N-Acetylcysteine at High Doses in Chronic Respiratory Diseases: A Review. Drug Saf. 2021;44(3):273-290. doi:10.1007/s40264-020-01026-y
[3] Khoshbaten M, Aliasgarzadeh A, Masnadi K, et al. N-acetylcysteine improves liver function in patients with non-alcoholic Fatty liver disease. Hepat Mon. 2010;10(1):12-16.
[4] Faghfouri AH, Zarezadeh M, Tavakoli-Rouzbehani OM, et al. The effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials. Eur J Pharmacol. 2020;884:173368. doi:10.1016/j.ejphar.2020.173368
[5] Sandhir R, Sood A, Mehrotra A, Kamboj SS. N-Acetylcysteine reverses mitochondrial dysfunctions and behavioral abnormalities in 3-nitropropionic acid-induced Huntington’s disease. Neurodegener Dis. 2012;9(3):145-157. doi:10.1159/000334273
[6] Virel A, Johansson J, Axelsson J, et al. N-acetylcysteine decreases dopamine transporter availability in the non-lesioned striatum of the 6-OHDA hemiparkinsonian rat. Neurosci Lett. 2022;770:136420. doi:10.1016/j.neulet.2021.136420
[7] Bradlow, R.C.J., Berk, M., Kalivas, P.W. et al. The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders. CNS Drugs 36, 451–482 (2022). https://doi.org/10.1007/s40263-022-00907-3
[8] Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-492. doi:10.1093/jn/134.3.489
[9] Tenório MCDS, Graciliano NG, Moura FA, Oliveira ACM, Goulart MOF. N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants (Basel). 2021;10(6):967. Published 2021 Jun 16. doi:10.3390/antiox10060967
[10] Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-492. doi:10.1093/jn/134.3.489
[11] Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease. Biomed Pharmacother. 2003;57(3-4):145-155. doi:10.1016/s0753-3322(03)00043-x
[12] Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335-344. doi:10.1113/jphysiol.2003.049478
[13] Li S, Fasipe B, Laher I. Potential harms of supplementation with high doses of antioxidants in athletes. J Exerc Sci Fit. 2022;20(4):269-275. doi:10.1016/j.jesf.2022.06.001
[14] Bradlow, R.C.J., Berk, M., Kalivas, P.W. et al. The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders. CNS Drugs 36, 451–482 (2022). https://doi.org/10.1007/s40263-022-00907-3
[15] University College London. (2022, July 20). No evidence that depression is caused by low serotonin levels, finds comprehensive review. ScienceDaily. Retrieved July 29, 2022 from www.sciencedaily.com/releases/2022/07/220720080145.htm
[16] Dionisie V, Filip GA, Manea MC, Manea M, Riga S. The anti-inflammatory role of SSRI and SNRI in the treatment of depression: a review of human and rodent research studies. Inflammopharmacology. 2021;29(1):75-90. doi:10.1007/s10787-020-00777-5
[17] Yang C, Bosker FJ, Li J, Schoevers RA. N-acetylcysteine as add-on to antidepressant medication in therapy refractory major depressive disorder patients with increased inflammatory activity: study protocol of a double-blind randomized placebo-controlled trial. BMC Psychiatry. 2018;18(1):279. Published 2018 Sep 4. doi:10.1186/s12888-018-1845-1
[18] Berk M, Dean OM, Cotton SM, et al. The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial. J Clin Psychiatry. 2014;75(6):628-636. doi:10.4088/JCP.13m08454
[19] Deepmala, Slattery J, Kumar N, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neurosci Biobehav Rev. 2015;55:294-321. doi:10.1016/j.neubiorev.2015.04.015
[20] Gray KM, Watson NL, Carpenter MJ, Larowe SD. N-acetylcysteine (NAC) in young marijuana users: an open-label pilot study. Am J Addict. 2010;19(2):187-189. doi:10.1111/j.1521-0391.2009.00027.x
[21] Bradlow, R.C.J., Berk, M., Kalivas, P.W. et al. The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders. CNS Drugs 36, 451–482 (2022). https://doi.org/10.1007/s40263-022-00907-3
[22] Berk M, Malhi GS, Gray LJ, Dean OM. The promise of N-acetylcysteine in neuropsychiatry. Trends Pharmacol Sci. 2013;34(3):167-177. doi:10.1016/j.tips.2013.01.001
[23] Sarris J, Byrne G, Castle D, et al. N-acetyl cysteine (NAC) augmentation in the treatment of obsessive-compulsive disorder: A phase III, 20-week, double-blind, randomized, placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2022;117:110550. doi:10.1016/j.pnpbp.2022.110550
