N-acetylcysteine has originally introduced as a mucolytic agent for chronic pulmonary diseases some 50 years ago. Therefore, it is primarily inhaled to manage conditions in which mucus is abnormally thick and tenacious.
Because it has strong nootropic effects, biohackers of our time love it very much. Beyond just being a powerful anti-oxidant, NAC also boosts mood, lowers anxiety, and improves memory (both short-term and long-term).
Today, NAC is on the World Health Organization’s list of valuable medicines.
NAC is a cheap vitamin-like medicine that is used as a prescription and over-the-counter drug.
It is actually a prodrug and precursor of the non-essential sulfur-containing amino acid in humans – Cysteine.
N-acetylcysteine is being discussed in over 10,000 scientific publications and over 300 human clinical trials in the past 10 years.
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My experience with NAC
After reading a lot of fascinating research data, I started taking the NAC supplement with a grain of salt. There is really excessive and uncontrolled information about NAC.
As cool as this supplement is, continued research still needs to inform us more in the future.
So is NAC good for the brain?
For this article, I did both anecdotal and scientific research. I have also studied NAC for my problems with sleep apnea and stress management.
I discovered better sleep patterns and less stress. I only take one 500 mg capsule a day. I haven’t had any side effects and I cycle off of it occasionally.
I noticed NAC works quickly for thinning mucus, and subtly for mood regulation, skin health, and energy benefits.
NAC help depends on the condition of your health, and it can improve your ability to eliminate oxidative stress.
As a referent point of NAC quality, one study said it greatly increases antioxidant status in about a week (4).
what does nac supplement stand for?
NAC is a derivative of cysteine, an amino acid that is naturally produced in the body by using another amino acid methionine.
Cysteine is a non-essential sulfur-containing amino acid in humans crucial for protein synthesis, cleansing, and also diverse metabolic functions.
Found in beta-keratin, the primary healthy protein in nails, skin, and hair,
cysteine is essential in collagen production, along with skin elasticity and
Likewise, called for in the manufacture of amino acid taurine, cysteine is a component of the antioxidant glutathione, and also contributes to the metabolic rate of crucial biochemicals such as coenzyme A, heparin, as well as biotin.
NAC is essentially a powerful anti-oxidant and cysteine/glutathione prodrug that is converted to cysteine in the intestine (by the enzyme aminoacylase 1) and absorbed into the bloodstream. Then it is rapidly metabolized and incorporated into proteins.
But, in general, little is known about the metabolism of this agent.
An acetyl group attached to the amino group of cysteine makes NAC more stable (which aids its shelf life) and allows the body to absorb and use it better.
NAC food sources
Cysteine is primarily found in animal proteins such as chicken, pork, sausage, turkey, fish, and duck. Dairy sources of cysteine include yogurt, ricotta cheese, eggs, and cottage cheese.
Cysteine is also found in some plant sources for vegetarians and vegans. Foods such as broccoli, red pepper, onion, granola, and oat flakes are all good sources of Cysteine.
Other sources include garlic, bananas, linseed, soybeans, and wheat germ.
Low levels of Cysteine can delay growth in children and lower immunity. Weakness and muscle loss may also occur as a result of a low Cysteine diet (5).
How NAC work?
Science has agreed that N-acetylcysteine helps us because of the multiple mechanisms of action (6).
Among its known mechanisms, NAC-induced brain glutathione (GSH) replenishment is the most studied.
According to studies, taking NAC increases your glutathione levels by more than 30 percent while the oxidative damage markers were reduced by more than 30% (7).
1. The antioxidant glutathione
Glutathione (GSH) is involved in the intracellular and extracellular detoxification of reactive oxygen species (ROS) and free radicals in the brain. It acts on every cell in the body which is essential to anti-aging benefits and optimal health with less stress.
GSH is particularly crucial for appropriate brain function, lung function, and liver detoxing procedures. Regarding glutathione’s chemical structure, it is not possible to effectively take glutathione as a supplement and absorb it.
Reliably raising natural glutathione in the body in just a few doses is what makes NAC a potent free radical scavenger. NAC participates in general antioxidant activities and raises the body’s natural defense system.
Glutathione that our body makes might be diminished in a variety of health conditions. So the levels of NAC is used to enhance the production of glutathione when it is normally depleted.
Among many, established roles for GSH are the following:
detoxification of electrophilic xenobiotics
modulation of redox (oxidation-reduction reaction)-regulated signal transduction
storage and transport of cysteine
regulation of cell proliferation, synthesis of deoxyribonucleotide synthesis
regulation of immune responses
regulation of leukotriene and prostaglandin metabolism
As one of the few natural mucolytic agents, NAC supplements separate mucus, specifically in the lungs and respiratory tract. Therefore, in addition to its glutathione-increasing mechanism, NAC is popular as a supplement for its ability to break up or loosen sputum making it easier to cough up.
NAC exerts its mucolytic action through its free sulfhydryl group, which reduces the disulfide bonds in mucus proteins and lowers mucus viscosity.
This action increases with increasing pH and is most significant at pH 7 to 9.
3. Glutaminergic transmission
This mechanism adds to the NAC nootropic effects.
NAC is a “glutaminergic” substance, suggesting it can regulate levels of glutamate, the most abundant excitatory neurotransmitter in the brain.
Glutamate is associated with a broad range of knowledge, habits, and memory.
NAC, for instance, has been shown to regulate the levels of excessive glutamate, which causes toxic damage in brain disorders like schizophrenia and drug dependency.
This mechanism of action of NAC is particularly important because of its effect on glutaminergic neurons in the nucleus accumbens, which is involved in the modulation of the reward and reinforcement center implicated in the addictive behaviors.
Metabotropic glutamate receptors
N-acetylcysteine also serves as a precursor to cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of acetylcysteine, mGluR5.
It has been suggested that mGluRs may act as regulators of neurons’ vulnerability to excitotoxicity (a deadly neurochemical process involving glutamate receptor overactivation) through their modulation of NMDARs, the receptor most involved in that process.
Therefore, NAC has an indirect and direct therapeutic effect on glutamate.
From the Longecity forum thread:
The decrease in glutamate means less impulsive behavior, so there is less smoking, less gambling in people with gambling disorders, and less hair pulling.
I use it, but I keep the dose small to avoid the potential pulmonory issues. Given the disorders it has been tested against (bipolar depression, OCD, etc), it’s more about what you don’t notice than what you do notice.
4. Dopaminergic transmission
Because NAC is such a powerful antioxidant and free radical scavenger that increases intracellular GSH at the cellular level, it can manipulate processes that rely on oxidation. Neuroscientists think that through modulation of oxidative and nitrative damage, NAC has also an impact on a dopaminergic process (8).
The newer preliminary study from 2016 laid the foundations for the evaluation of NAC on dopamine release in the brain, as seen in the Parkinson’s disease model. Patients were evaluated before and after 3 months of receiving the NAC to measure dopamine transporter (DAT) binding and the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure clinical symptoms (9).
This study demonstrated for the first time the direct effect NAC has on the dopamine system in PD patients. A large-scale clinical trial is needed to test the therapeutic efficacy of NAC in this population.
It seems NAC has the ability to recover dopamine neurons and their function in the brain.
Two animal studies shed some light too.
In the first, N-acetylcysteine alters dopamine release. Following amphetamine treatment to rat striatal slices, NAC has been shown to facilitate vesicular dopamine release at low doses in striatal neurons and inhibit release at millimolar concentrations.
In monkeys, NAC has been shown to protect against reductions in DA transporter levels following repeated methamphetamine administration, suggesting one mechanism whereby increased DA release was facilitated in the previous study. Glutathione has also been shown to increase glutamate agonist–evoked DA release in mouse striatal neurons.
This one general thought comes from one year ago from a Reddit thread and sums it up:
Would this likely be useful as a general neuroprotective agent for the dopamine system in healthy, non-meth-using people, by protecting from normal or environmental causes of oxidative stress? Would reduction of normal dopamine oxidative stress likely have some effect on conditions dependent or partially dependent on dopamine, like depression (Which, if I recall correctly, has some significant neurotoxicity of its own)?
5. inflammatory pathways
NAC also favorably affects the expression of genes involved in the inflammatory response, modulating them at the molecular, cellular, organ, and whole-body levels.
By increasing your glutathione levels, NAC makes you much more resistant to inflammation and oxidative stress and slows down aging at a cellular level.
With regards to anti-inflammatory activity, several research studies have observed that NAC is able to limit cytokines release in the early state of immune proliferation (10). Additionally, in animal models, inflammatory markers induced by lipopolysaccharides are influenced by the modulation of NAC. NAC also possesses some anti-inflammatory effects possibly via inhibiting NF-κB through redox activation of the nuclear factor kappa kinases thereby modulating cytokine synthesis.
The inflammatory-modulating effects of NAC may be important for its mood-stabilizing efficacy. It is recently observed in the effects of systemic inflammation in bipolar disorder patients.
In several cellular systems, NAC promotes effects aimed to maintain the survival functions of cells, which also induces the production of intracellular GSH known as the principal antioxidant produced by the body that protects cells from oxidative stress and maintains the redox state inside them.
6. mitochondrial enhancer
In recent years NAC is also studied as a mitochondrial enhancer.
In psychiatry, chronic stress has been shown to induce mitochondrial dysfunction, ultimately leading to apoptosis or cell death.
Treatment with NAC prolonged the survival of cells obtained from a patient with a mitochondrial disease like bipolar disorder. Thus, the neuroprotective properties of NAC may be related to its neurogenesis-inducing ability, which is likely related to mitochondria-protective mechanisms.
As far as it seems, NAC may be the first pharmacological intervention that increases mitochondrial resilience and prevents allostatic load in psychiatry (Kapczinski et al.) (11).
Is NAC a nootropic?
Is NAC a nootropic? That is heavily questioned on social media, on Reddit, and also elsewhere. For some it is not a performance enhancer, for others, it works like a memory and also energy levels booster.
In anecdotal as well as scientific research studies it mostly serves for therapy of neurological deficits or adjunctive tool in professional experiments.
It’s my viewpoint that it feels like a nootropic equally with some better known like Noopept, or piracetam.
- NAC is helpful for synergy with various other nootropics.
- The strong side of supplementing with NAC is that it has a really secure profile.
- The systems underlying the therapeutic as well as clinical applications of NAC are intricate as well as still unclear.
However, we recognize it has brain benefits due to the fact:
- Prevent glutamic toxicity
- Increases dopamine
- Lowers inflammatory paths
- Free radical scavenger
- NAC affects the amounts of dopamine in the brain by regulating glutathione
From lots of anecdotal testimonials of memory-enhancing properties, I like this one from the WebMD site.
My memory was extremely poor all my life so as to present me with serious problems managing my life. Therefore, I don’t remember why my old naturopath prescribed NAC for me. But I will never stop taking it because within 3 weeks of a daily dose, I began to have recall: I recalled clearly when I had last taken my medications. It had been the day before. I write this many years later and I still remember what my first memory was. Before then, I’d had huge problems with trying to remember if I’d taken my medications. Even the weekly pill boxes didn’t work. I’d simply forget to go to them. (This was before ubiquitous cell phones with programmable alarms.) NAC really changed my life. I don’t know why it helps my memory or if it would help anyone else’s.
NAC mental health benefits
Among many benefits of NAC supplement, these nootropic effects on mental health are seen:
- Neuroprotection. NAC as a precursor of glutathione works anti-inflammatory, and, due to its interaction with ROS, is an efficient scavenger of free radicals (12). Your brain is especially vulnerable to the free radicals attack intracellularly, which causes oxidative damage to the tissue. NAC thus affects cognition, long-term potentiation, memory, and mood.
- Neurotransmitters support. NAC modulates glutamate levels and dopamine release in the brain. Thus affecting neuron health, cognition, memory, and mood. NAC also controls dopamine levels and function in your brain and protects dopamine receptors (13).
- Anti-anxiety and mood booster. NAC reduces irritability, anxiety, and depression in psychiatric disorders. NAC increases your body’s antioxidant capacity and balances excitatory and inhibitory neurotransmitters in your brain. Resulting in less anxiety and depression (14).
Can Nac cross blood-brain barrier?
The ability of the compound to cross the blood-brain barrier (BBB) is thought to be critical to the treatment of brain dysfunction.
Although the NAC’s ability to cross BBB is being disputed, it completely relies on its form, dose, and routes of administration.
Some studies report that intravenous (jugular) and intra-arterial (intracarotid) administration of 14C-NAC resulted in good BBB permeability.
Recent studies have demonstrated the blood-brain barrier permeability and therapeutic potential of N-acetylcysteine amide (NACA) in neurological disorders (Sunitha et al. 15).
The dramatic increase in the brain levels of NAC and cysteine happened with the administration of NAC ethyl ester, probably due to its rapid hydrolysis.
Further studies are required for determining its ability to cross the cell membrane and the blood-brain barrier as well as elucidating its reactions with components of cell signaling pathways (16).
Stacking NAC with nootropics
Nootropic Ingredients like alpha-lipoic acid (ALA), n-acetyl cysteine (NAC), and acetyl L-carnitine (ALC) can mitigate metabolic waste and maximize the energy potential of the cell. The combination allows more efficient energy production via mitochondrial and metabolic pathways and quicker muscle recovery due to enhanced glutathione regeneration.
You may add quality magnesium (like L-threonate) and ashwagandha into the stack for less brain fog, and burnout properties. People report that it is good for treating fatigue and depression after the use of prescribed stimulant medicines like Vyvanse.
N-acetylcysteine and L-theanine combo will be great as an anti-anxiety stack. People also make use of it as a sleep aid. Taking NAC with quality KSM-66 or Sensoril (standardized) ashwagandha will also do the trick.
NAC supplement side effects
Oral NAC supplements are generally safe and well-tolerated, but sometimes when the concentrations are too high it might cause side effects such as diarrhea, nausea, vomiting, or constipation.
It’s hard to take it as it has an unpleasant odor due to its sulfur origin.
To quote one funny commentary on NAC from the Longecity:
makes me feel worse…don’t put this snake-oil into your body
It certainly is not for everyone, mainly because of abuse. Or if you do not need it, but still take NAC without consultations with your doctor.
It is reported that doses of 500-1800 mg daily are safe (113).
What are the risks of taking NAC?
- NAC can cause Irritable Bowel Syndrome (IBS) symptoms.
- Aerosol NAC can cause swelling in the mouth, runny nose, drowsiness, and chest tightness.
- Increased heart rate
- Skin rash
- Irritated eyes
Avoid dietary supplement NAC if you take nitroglycerin or antidepressant medications, advises Memorial Sloan Kettering Cancer Center.
Who should avoid taking NAC?
- Spasm of the lung airways
- NAC may interfere with blood clotting. Since NAC can impact the platelets and reduce coagulation, people with bleeding disorders or taking blood-thinning medications should not take NAC.
- NAC can decrease blood pressure. NAC may interact with medications, causing seriously low blood pressure and headaches., dizziness or fatigue.
- NAC may cause an allergic reaction in certain individuals. A severe allergic reaction, called an anaphylactoid reaction, may occur after initial treatment with NAC supplements. That could cause breathing problems, difficulty swallowing, facial swelling, hives, weakness, dizziness, or pale skin. Seek emergency medical care if you exhibit any of these symptoms after taking a NAC.
Avoid taking NAC with nitroglycerin. Nitroglycerin is a medication prescribed for chest pain and a potent vasodilator. NAC is also a vasodilator. If taken together, this could result in severely low blood pressure, lightheadedness, loss of consciousness.
It can also induce an asthma attack and cause anaphylactic shock, which is a life-threatening reaction.
Trace minerals depletion?
It has been suggested that NAC may increase the excretion of trace minerals; some evidence, however, suggests that this effect is too minimal to make a real difference.
Researchers suggest individuals taking NAC for an extended period of time should also consider taking a standard multivitamin/multimineral supplement. Especially watch to add zinc and copper minerals after the prolonged use of NAC.
Best NAC supplement
NAC is available for sale in many neighborhood pharmacies as well as supermarkets and online stores. It is best to purchase NAC online because you have full control over safety and quality. That way you can investigate all the best prices as well as active ingredients. I particularly like this vendor because it provides several solutions such as capsules, powder, and bulk NAC.
Hard Rhino Supplements is a reputable and many people’s favorite online supplier of a wide range of high-quality lab-tested ingredients. Based out of Phoenix, Arizona, and with a background of 25+ years in the supplement industry, they manage multiple supplements in a variety of categories such as bodybuilding, joint pain, cognitive health, nootropics, and much more.
They are located in an FDA-regulated facility and are known for the high-quality lab-tested ingredients. Their innovative access to the certificate of authenticity (COA) on all product pages is something that is most welcomed among online vendors. I cheer for that practice.
FAQs ABOUT nAC
NAC is helpful for most bio-hackers to improve mood, memory, cognition, and concentration. And NAC helps alleviate brain fog, anxiety, and irritability.
Some of these outcomes you can look forward to if you take NAC.
- Less brain fog – more clear thinking
- Short-memory and long-memory improvement
- Concentration and attention enhancing
- Less anxiety
- Less depression
- Less irritable
- Mood improves
- Symptoms caused by ADHD meds disappear
- Obsessive-Compulsive behavior decreases
- Sleep quality improves
- Energy levels increase
- Weight maintenance is easier
- Less flu and colds
- Skin looks better
- Feel younger
- Hangovers are less severe
Yes, oral NAC supplements are secure as well as generally well tolerated. The optimal dose of NAC is 600 mg 2 to 3 times a day. If you have never tried it, start with 300 mg and work your way up slowly.
NAC may also infrequently cause looseness of the bowels, queasiness, as well as throwing up.
A shortage of cysteine amino acid is probably to happen in individuals that are unable to biosynthesize it, such as the elderly as well as babies. People with malabsorption problems along with metabolic conditions might additionally be not able to synthesize adequate quantities of l-cysteine.
An l-cysteine shortage may cause a jeopardized body immune system, which can cause slow-moving healing from injury in addition to conditions.
Added signs that you may require l-cysteine include fragile nails, acne, and additionally scar tissue.
In fact, because of its sulfur content, NAC supplements can smell like rotten eggs—so take capsules without sniffing or worry too much!
Taking it on an empty stomach is perfect if you can take it that way without disturbances.
Just like other amino acid supplements, NAC should be taken either 30 minutes before, or two hours after eating to avoid competing with protein for absorption.
Glutathione has been known to lighten the skin and since NAC is a precursor to glutathione, NAC can also be responsible for some skin lightening.
Not directly, however, NAC may play a role in the treatment of diabetes mellitus due to its ability to improve insulin sensitivity and reduce fasting blood insulin levels.
If you are taking antibiotics, NAC should not be taken, as it may weaken their beneficial effects.
Although the FDA suppressed the use of NAC in dietary supplements in 2010, in the last year the ban was significantly strengthened due to new clinical research on the use of NAC for COVID-19.
The treatment with inhaled or intravenous pharmaceutical forms of NAC is used in patients with COVID-19. There are now 19 clinical studies of NAC for COVID-19 care in the government’s Clinical Trials registry.
While The FDA claims that including NAC in a supplement makes the product an unapproved drug and therefore illegal, as of August 2022, they back away from its tough stance. They state that it was considering a rule allowing NAC to be sold as a dietary supplement. Until a final decision is made, the FDA intends to exercise discretion over NAC dietary supplement products until safety concerns are identified.
Taking NAC is possibly the most effective and most useful method to get endogenous glutathione that flows.
This comes with such a large range of benefits as well as possible applications throughout numerous conditions as well as systems.
NAC is really safe to take, and you will have time to see whether you need it or not. I have it on my brain-hack list for some time as one of the most indispensable supplements. I usually take 500 mg per day and cycle off NAC regularly.
How beneficial the NAC is will hinge on a few rules. Poor sleep, inadequate diet regimen, and also undesirable lifestyle will cause even more need for glutathione.
As a general word of warning, just like every antioxidant nutrient, NAC in restorative doses (as low as 1.2 g day-to-day) can potentially have pro-oxidant activity, and also therefore it is not suggested in the lack of a considerable validated oxidative stress.
For healthy and balanced individuals that have an optimized glutathione level the most logical suggestion is to cycle the NAC or otherwise not exaggerate it.