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N-Acetylcysteine (NAC)

Summary: N-acetylcysteine (NAC) is a medication that may possibly be helpful in the treatment of various mental health conditions.
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What is N-Acetylcysteine?

N-acetylcysteine (NAC) is a dietary supplement that comes from the amino acid L-cysteine. It is an antioxidant, and appears to help by protecting vital components (such as DNA) against oxidative damage, and appears to be helpful in various conditions including brain conditions. 

How does N-Acetylcysteine Work?

Oxidation is a normal process that takes place in your body. However, this process can become imbalanced, leading to excess “oxidative stress”, which can cause damage in your cells.

NAC can help protect the body from oxidative stress. NAC is used by the body to make brain glutathione, which is an antioxidant. 

Normal Dietary Sources of Cysteine

Cysteine normally comes from the protein in the diet. 

However, in certain conditions, the body may require more cysteine than is present in the diet, such as when people have 1) poor appetite, and/or 2) processed food that lacks sulfur-containing amino acids (SAA).

What Might It Be Helpful For?

N-Acetylcysteine (NAC) is a treatment for acetaminophen (aka paracetamol) overdose. When people take an overdose of acetaminophen, this depletes glutathione (GSH), which can then lead to liver damage. The solution? Giving NAC provides cysteine necessary to replace depleted glutathione (GSH) which then prevents liver injury.

NAC may also be helpful in other conditions where there is oxidative stress such as the following (Deepmala, 2015):

  • Alzheimer disease
  • Mood conditions such as depression and bipolar;
  • Trichotillomania, nail biting, skin picking, obsessive-compulsive disorder (OCD)
  • Autism;
  • Cocaine and cannabis addiction,
  • Schizophrenia,
  • Drug-induced neuropathy.

There is preliminary evidence for the following conditions, though more studies are required (Deepmala, 2015):

  • Anxiety,
  • Attention deficit hyperactivity disorder
  • Mild traumatic brain injury

Evidence does not support the use of NAC with gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis.

As research is limited with NAC, it is generally not recommended unless more commonly accepted treatments have already been tried first.

A Word of Caution: Negative Evidence

Although there was initial promising evidence, two later meta-analyses have been less encouraging for major depression and bipolar disorder.

“... evidence does not encourage the use of NAC as an augmentation treatment for patients with MDD or BD. It remains to be seen whether NAC augmentation benefits depressed subpopulations, such as those with higher levels of inflammatory biomarkers at baseline.” (Andrade, 2021).

What Dosages?

Condition

Dosage

Reference

Treatment resistant obsessive compulsive disorder (OCD)

Adults: Start 1000 mg twice daily x 1-week, then increase to 1500 mg twice daily

Couto, 2018


Adolescents: Start 600 mg twice daily and move up to 1200 mg twice daily

Arnold, 2020

Adjunctive treatment in bipolar depression

Adults: 1000 mg twice daily

Berk et al., 2011

Trichotillomania

Adults: 600-1200 mg twice daily

Grant, 2009

Most studies on NAC have been in adults. Few (if any studies) have looked at dosages for children and adolescents.

Where to Find it?

NAC can be found in drug stores, natural health foods stores and online retailers.

As NAC is a supplement, note that NAC is not regulated in the same manner as standard conventional medications might be. There may be significant variations between manufacturers in terms of purity and the active ingredient.

References

Andrade C. N-acetylcysteine augmentation for patients with major depressive disorder and bipolar depression. J Clin Psychiatry. 2021;82(1):21f13891.

Arnold, P. CACAP Conference: Group 1 Discussion with Dr. Paul Arnold, 2020.

Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, et al. N-acetyl cysteine for depressive symptoms in bipolar disorder–a double-blind randomized placebo-controlled trial. Biol Psychiat. 2008;64(6):468–75.

Berk M, Dean O, Cotton SM, Gama CS, Kapczinski F, Fernandes BS, et al. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord. 2011b;135(1–3):389–94.

Couto JP, Moreira R. Oral N-acetylcysteine in the treatment of obsessive compulsive disorder: a systematic review of the clinical evidence. Prog Neuropsychopharmacol Biol Psychiatry

2018;86:245-54.

Deepmala D et al.: Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neuroscience and Biobehavioural Reviews. 2015; 55: 294-321.

http://dx.doi.org/10.1016/j.neubiorev.2015.04.015

Dean O et al.: N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011 Mar; 36(2): 78–86.

https://www.sciencedirect.com/science/article/pii/S0149763415001190?via%3Dihub

Grant J et al.: N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. 2009 Jul;66(7):756-63. doi: 10.1001/archgenpsychiatry.2009.60.

https://www.ncbi.nlm.nih.gov/pubmed/19581567

About this Article

Written by the health professionals at the Children’s Hospital of Eastern Ontario (CHEO) in Ottawa, Ontario, Canada. Special thanks to Dr. Paul Arnold for information about NAC dosages in adolescents.

Conflicts of interest: The authors have no competing interests to declare.

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Disclaimer

Information in this pamphlet is offered ‘as is' and is meant only to provide general information that supplements, but does not replace the information from your health provider. Always contact a qualified health professional for further information in your specific situation or circumstance.



Date Posted: Sep 18, 2020
Date of Last Revision: Feb 2, 2022

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