N-Acetyl L-Cysteine (NAC) is an amino acid with very powerful antioxidant activity. It is a well-researched supplement with a great deal of practical utility. When supplemented, the benefits of NAC are plentiful – it is even used by hospitals and other medical industries due to its remarkable neurogenic healing properties.
NAC is simply the acetylated form of the amino acid L-Cysteine – in this form it is easily able to get absorbed into the bloodstream and cross the blood-brain barrier.
N-Acetyl Cysteine, when supplemented, primarily works by enhancing the production of glutathione, a powerhouse antioxidant that provides numerous benefits throughout the body.1https://www.ncbi.nlm.nih.gov/pubmed/23731375
Glutathione is a naturally-occuring antioxidant that our own body uses to prevent cellular damage from free radicals, heavy metals, and other damaging reactive oxidants. Interestingly, supplementing glutathione directly is ineffective due to poor absorption rates, but NAC is able to encourage production of glutathione to a substantial degree through a series of chemical reactions.1https://www.ncbi.nlm.nih.gov/pubmed/23731375
While many foods, supplements, and herbal products claim antioxidant status, the degree of antioxidant activity needs to be taken into account. It’s probably not fair to lump NAC with other antioxidants as it is considerably more powerful than almost everything else out there.
NAC is already used in hospitals for treating liver damage from alcohol and acetaminophen2https://pubmed.ncbi.nlm.nih.gov/4842541-protection-against-acetaldehyde-toxicity-in-the-rat-by-l-cysteine-thiamin-and-l-2-methylthiazolidine-4-carboxylic-acid/11https://www.ncbi.nlm.nih.gov/pubmed/24708414], and there is emerging evidence that NAC may be able to help treat numerous neurological disorders as well.26https://onlinelibrary.wiley.com/doi/full/10.1002/brb3.208
For those of you unfamiliar with NAC, this post will get you up to speed on the latest evidence-based information on NAC and summarize why you may want to include it in your nootropic stack.
Benefits of NAC Supplementation
The benefits of n-acetyl cysteine range from improved brain and organ health to improved respitory health, skin health, and elevated mood.
One of the most common uses of NAC is for preventing the negative effects of alcohol, especially liver toxicity and hangovers.2https://pubmed.ncbi.nlm.nih.gov/4842541-protection-against-acetaldehyde-toxicity-in-the-rat-by-l-cysteine-thiamin-and-l-2-methylthiazolidine-4-carboxylic-acid/
One other major reason to supplement NAC is for the brain health benefits, which result from primarily from powerful antioxidant activity and glutamate modulation.
NAC shows great promise for improving overall mental function and wellbeing, which is likely a secondary, indirect consequence of the improved brain brain.
One of the more under-appreciated potential uses of NAC is for treating drug addiction, which has very encouraging scientific studies as of 2020.
Many studies surrounding NAC supplementation studies were done within the context of specific drug addictions (particularly cocaine, nicotine, and marijuana). However, it is not a stretch to hypothesize that NAC may have a generalized anti-addictive quality that can apply to behavioral addictions as well.
The reason why NAC may have a universal anti-addictive quality is because many addictions share very similar pathlogical and neurological mechanisms (neuropathology) in the brain. Before learning why NAC may benefit addiction, it may be helpful to understand some basic mechanisms that underlie the addictive processes in the brain.
The Neurology of Addiction
There are a few distinct ways to define addiction, and for the sake of simplicity it may be easier to focus on the neurology rather than the psychology.
In contrast with the older models of addiction, the more recent clinical literature has described addiction as “pathological learning.”3http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.335.7517&rep=rep1&type=pdf4https://www.ncbi.nlm.nih.gov/pubmed/16055762 Essentially, the pathological learning model suggets that the brain learns to associate certain actions with reward, despite negative consequences.
Reward is a driving factor in all human behavior and is one of the primary mechanism for all addictions. While dopamine is known to play a large role in reward-based behavior, there is another key neurotransmitter that is rarely discussed: glutamate.
Glutamate performs countless functions in the brain and is almost unquestionably most important for overall mental functioning. Glutamate is highly involved neuroplasticity – structural changes in the brain that occur over time. As such, it is no surprise that glutamate can become highly dysfunctional in people with addictions due to long-term pathological learning.
Indeed, glutamate has been suggested to be a key player in the neurochemistry of addiction.5https://www.sciencedirect.com/science/article/abs/pii/S00283908080028886https://www.sciencedirect.com/science/article/pii/B978012800634400010X
With this all in mind, NAC works by restoring optimal glutamate function in the brain. While it does not act a glutamate antagonist, it does help maintain and restore normal glutamate activity.7https://www.ncbi.nlm.nih.gov/pubmed/16000629 This effect has been found to be even more pronounced in the brains of drugs addictions; as such NAC has seen increased evidence as an effective treatment for cocaine8https://www.ncbi.nlm.nih.gov/pubmed/22549117, nicotine9https://www.ncbi.nlm.nih.gov/pubmed/19103434, and marijuana.10https://www.ncbi.nlm.nih.gov/pubmed/20163391 While there is insufficient evidence to determine the effect of NAC supplement on other forms of addiction, it’s not a stretch to assume it has similar benefits since almost all addictions share similar neurological mechanisms.
Antioxidant & Anti-Inflammatory Properties
Detox from heavy metals and free radicals
Two studies were done to determine the effects of NAC administration on workers who were chronically exposed to lead. NAC supplementation was found to rapidly eliminate significant amount of lead in the workers, primarily by increasing the amount of antioxidant enzymes in both red and white blood cells.1https://www.ncbi.nlm.nih.gov/pubmed/2373137514https://www.ncbi.nlm.nih.gov/pubmed/25731901
Pesticides are an emerging concern among the health-conscious population as well. Current research on NAC indicates it may be a powerful way to “detox” from the systematic effects of pesticides on the the body.15https://www.ncbi.nlm.nih.gov/pubmed/2694630816https://www.ncbi.nlm.nih.gov/pubmed/2678604217https://www.ncbi.nlm.nih.gov/pubmed/23148565 Again, the mechanism of action suggests it works through rapid interaction and elimination of free radicals.
Administration of NAC has been found to prevent damge from other common toxic compounds as well. This includes silica, a mineral that is commonly released from rocks during construction which can damage the lungs when inhaled18https://www.ncbi.nlm.nih.gov/pubmed/24370303. Some studies have even found it may help prevent or reduce damage from chemotherapy and xrays, especially damage to the brain and DNA.19https://www.ncbi.nlm.nih.gov/pubmed/1645008920https://www.ncbi.nlm.nih.gov/pubmed/28034704
One rat study found that NAC has a protective effect against acetaldehyde, a byproduct of alcohol consumption.2https://pubmed.ncbi.nlm.nih.gov/4842541-protection-against-acetaldehyde-toxicity-in-the-rat-by-l-cysteine-thiamin-and-l-2-methylthiazolidine-4-carboxylic-acid/
NAC is commonly also used to heal the liver after damage from acetaminophen, and the current evidence is overwhelming for its effectiveness.11https://www.ncbi.nlm.nih.gov/pubmed/2470841412https://www.ncbi.nlm.nih.gov/pubmed/19169150
Some preliminary evidence indicates that NAC may be effective at improving skin health by reducing inflammation and improving cellular health.21https://www.ncbi.nlm.nih.gov/pubmed/2334666222http://www.ijdvl.com/article.asp?issn=0378-6323;year=2018;volume=84;issue=6;spage=652;epage=659;aulast=Adil
There is some early evidence that suggests NAC can improve mood, especially a reduction of depression.25https://www.ncbi.nlm.nih.gov/pubmed/1958156728https://www.ncbi.nlm.nih.gov/pubmed/25004186 The mechanism behind this anti-depressive effect does indeed come from the anti-inflammatory and glutaminergic-restoring properties, which further helps demonstrate a systematic benefit to brain and body function.
One systematic review and meta-analysis of NAC sought to determine its effectiveness in treating depression. After filtering for double-blind, randomized, placebo-controlled studies, five studies were analyzed. The authors found that subjects did indeed show a notable reduction of depressive symptoms based on a depression rating scale.27https://www.ncbi.nlm.nih.gov/pubmed/27137430
There are some early studies have noted that the antidepressive benefits of NAC may also apply to people with bipolar disorder.29https://pubmed.ncbi.nlm.nih.gov/22189927-n-acetylcysteine-for-major-depressive-episodes-in-bipolar-disorder/ Another study found it may even be able to help reduce mania and hypomania, which is the other side of bipolar disorder.30https://pubmed.ncbi.nlm.nih.gov/23493756-a-preliminary-investigation-on-the-efficacy-of-n-acetyl-cysteine-for-mania-or-hypomania/
Currently, the evidence for NAC in treating OCD is limited, but the initial results definitely warrant further investigation.
Two randomized, double-blind, placebo-controlled trial examined the effects of NAC supplementation on patients with moderate to severe obsessive-compulsive disorder. Both studies found that it was able to significantly reduce OCD symptoms31https://pubmed.ncbi.nlm.nih.gov/26931055-n-acetylcysteine-augmentation-therapy-for-moderate-to-severe-obsessive-compulsive-disorder-randomized-double-blind-placebo-controlled-trial/32https://pubmed.ncbi.nlm.nih.gov/23131885-n-acetylcysteine-add-on-treatment-in-refractory-obsessive-compulsive-disorder-a-randomized-double-blind-placebo-controlled-trial/. It should be noted however that this research is still in the early stages and at this time NAC may better be thought of as an adjunct treatment rather than a primary treatment.
Final Analysis & Review of NAC
In short, the primary benefits of n-acetyl cysteine supplementation occur in the brain, particularly from very powerful antioxidant activity and regulation of the neurotransmitter glutamate.
High levels of glutamate causes excessive neuronal stimulation, leading to neurotoxic effects, pathological learning, and is strongly suspected to be the neurophysiological basis for many mental disorders.
This over-excitation of cells by glutamate is often referred to as excitotoxicity, and can lead to cognitive problems if not addressed.
Excitotoxicity is not generally something to worry about unless you abuse drugs. And while MSG (monosodium glutamate) was once suggested to cause excitotoxicity, this myth has since been debunked.
However, the possibility of dysfunctional glutamate activity is still possible for the average person, and it can cause poor focus and brain fog in some cases. As such NAC is powerful neuroprotectant and may be useful for maintaining healthy brain function as we age.
Furthermore, the antioxidant and anti-inflammatory properties are strong enough to provide systemic benefits to many organs throughout the body, and it’s not exactly clear who wouldn’t benefit from occasional NAC supplementation.
It is important to mention that NAC is not something to be taken casually, it is a seriously powerful supplement that a normal, healthy person does not necessarily need to take. However, it may be an effective tool for maintaining optimal brain health over time, when taken sparingly at low-doses.
Where to Buy NAC Capsules
NAC Dosage Information
For general brain health and antioxidant/detox purposes, 500mg-1000mg daily is recommended. It may be advisable to take it in cycles of two weeks or so ie two weeks on, two weeks off, to minimize possible side effects.
For reducing addiction, studies used 2400mg of NAC per day, usually split between 2-4 doses.
NAC Side Effects
The side effects of NAC should be discussed briefly because they are not completely benign. Even though no human studies have found any major side effects, this does not mean care should be exercised when taking this supplement. One rat study suggested that NAC may degrade the blood-brain barrier and cause micro-bleeding in the brain of stroke-prone rats, when taken at chronically high doses.23https://www.ncbi.nlm.nih.gov/pubmed/24898644 This does not necessarily warrant any concern, though it is not something to completely throw out either.
However, it should be noted that multiple human studies have found no harmful side effects from long-term NAC supplementation. One study did note that NAC is such a powerful antioxidant that may not be advisable to take it at it chronic, high doses as this may eventually lead to a paradoxical effect and do more harm than good (basically, too much of a good thing).24https://www.intechopen.com/books/free-radicals-and-diseases/free-radicals-and-neuronal-recovery-from-an-ischaemic-penumbra-a-review
So while NAC is almost certainly safe for the average person, it’s still strongly recommended to stick to a modest dosing regime. Always check with your doctor before taking a new supplement, especially something as potent as NAC.
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