N-Acetyl Cysteine

 
N-Acetyl Cysteine
By Jonathan Roseland  Connect    

NAC (which I’ll refer to it from now on) is a slightly modified version of the sulfur-containing amino acid cysteine. NAC is especially useful to those who have succumbed to vice but as a general Biohack, its effect on glutathione is most interesting.

This article is mostly going to focus on decoding what the human studies are saying about NAC and how this squares up with the anecdotal experiences of Biohackers online. For more of my own personal experiences, thoughts and comparisons please see the written and video reviews in the sidebar.

Scientific Research

NAC has been researched thoroughly by institutions worldwide, it’s discussed in the titles or abstracts of over 10,000 scientific publications listed on Pubmed, 300 human clinical trials have been done in the past 10 years alone which is impressive when you consider that it’s a none-patented, inexpensive supplement.

A Dr. Julius Goepp called it an Overlooked Compound That Saves Lives, writing

The sad consequence is that most aging individuals have never heard of it. Even many doctors remain unaware of its potential role as a frontline defense against some of today’s most deadly public health threats...

Glutathione Hack

Glutathione

When taken internally, NAC replenishes intracellular levels of the master antioxidant glutathione. The idiosyncratic transhumanist Aubrey De Grey is famous for saying that

“Breathing is bad for us”

Which may sound absurd but it's actually quite true, just like iron rusts or bread goes bad when left out because of oxidation, our internal organs are oxidized over time. Because we all enjoy breathing oxygen we often forget that it’s actually a poison, thankfully our distant microbial ancestors figured out how metabolize it! Glutathione is key to our individual cell’s ability to repair damage from oxygen.

In fact the main mechanism of action for NAC is being a substrate for.
Glutathione (GSH) which is an antioxidant used by every cell and tissue in the body. Although critical to a number of processes, it has limited use as a dietary supplement due to rapid breakdown during oral ingestion. Glutathione is capable of preventing damage to important cellular components caused by reactive oxygen species such as free radicals, peroxides and lipid peroxides.

Glutathione is maintained in its normal form by NAC, which increases its levels and takes heavy metals out of the body. That’s why Glutathione is the master antioxidant in the human system.

NAC Glutathione

History

NAC has been used in conventional medicine for more than 30 years, primarily as a mucolytic (mucous-thinner) inhaled to manage conditions such as cystic fibrosis, in which mucus is abnormally thick and tenacious - which just sounds delicious doesn't it?

Is NAC a Nootropic?

A few Biohackers on Reddit.com make it sound like NAC is a really good nootropic:

It consistently works for me. I've tried it over 10 times now, independently, each time responding extremely well. Dosage = 500mg It shuts off all of my anxiety and negative thoughts. It helps me lock on to a task (study) It gives me mental clarity and a clean stimulation. It seems like NAC and my brain are a perfect fit. “;

I've been taking about 1800mg NOW NAC for about two months now. It does seem to be stabilizing my emotions, reducing food cravings, clearing my mind and helping me focus without the "stimmy" feeling of noopept, piracetam or phenylpiracetam. WHile I enjoy that feeling of energy it feels a little unnatural, but NAC just feels normal and natural. It doesn't feel like I'm getting some sort of super boost, just that I'm performing a little closer to peak on a regular basis , with no side effects or come down. ;

An American commented on Longecity.com:

I was totally caught off guard by the effects of NAC on energy levels. I had no idea it would boost energy so dramatically. 500mg gives me a wonderful boost that lasts through most of the day. I tried consistent dosing of 500mg BID for a course of 3 weeks and noticed clearer and thinner mucous with a more productive cough as well (back when I was smoking heavily).

Despite these positive anecdotal reports I don’t really consider it a classic Nootropic or smart drug because

  • No notable studies mentioned an effect on cognition or memory.
  • In the anecdotal cases where Nootropic effects are reported it seems that it is treating neurological deficits. I don’t think it’s a performance enhancer.

As a nootropic NAC helps

  • Prevent glutamic toxicity
  • Boosts dopamine
  • Reduces inflammation
  • Free radical damage
  • NAC influences the amounts of dopamine in the brain

NAC is the N-acetyl form of the naturally occurring amino acid L-cysteine. L- cysteine is naturally produced in your body using the amino acid methionine.

Vs Flu and the common Cold

One larger study with older adults in Italy took like 600 milligrams of NAC twice a day for 6 months. Only 25% of the adults who used NAC experienced any kind of flu-like illnesses compared to 75% of the placebo group.

NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group...
Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment. Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals.

I’d categorize it as a preventative immune biohack, if you feel like you’re getting the flu it’s probably too late to start taking NAC, I’d suggest some of these more short-term immune biohacks.

Vs Autism

NAC has been used in attempts to help individuals with Autism spectrum disorders.
There have been over 20 clinical trials in the past 5 years where such patients were treated with NAC. Let’s take a closer look at a few...

In a randomized double blind, placebo controlled 2013 Iranian clinical trial it was added to risperidone for treating irritability in children and adolescents. The conclusion was that

Risperidone plus NAC more than risperidone plus placebo decreased irritability in children and adolescents with [Autism]. Meanwhile, it did not change the core symptoms of autism. Adverse effects were not common and NAC was generally tolerated well.
The use of dietary supplements in children with autism seems to be a safe practice with encouraging data about their clinical efficacy.

In a 12-week randomized double-blind, placebo-controlled trial of oral NAC in American youth with Autism, the participants were chosen via a computer to active drug or placebo in a 1:1 ratio, with the target dose of NAC being 60 mg/kg/day in three divided doses. The results indicated that NAC enhanced the glutathione levels as expected but had no significant impact in children with Autism.

Another American study from 2012 supported its potential usefulness for treating irritability in patients with Autism compared with placebo, NAC resulted in significant improvements.

A Longecity American user talks about their own experience with NAC and Autism:

Right now I'm testing some things on three people who could be said to be in a sorry hyperglutamatergic state; two of them are autistic and the third has OCD and a history of vasovagal syncope with grand mal seizures. All have responded well to NAC, and for the last four days I've added in faso and coluracetam.

This mom reported some improvement for her child, after he started using NAC:

We are trying it as well. My teenage son is on the autistic spectrum and also has OCD. He has a good doctor, who specializes in both ASD and OCD. Per the doctor’s orders, we started our son on 600 milligrams of NAC, twice a day. After three days of no noticeable side effects, we then increased it to 1,200 milligrams twice a day. So far, so good.

People who have OCD and ADHD have glutathione deficiency in their bodies. NAC has been proven of all supplements to be one of the best precursors of producing glutathione in the gut.

Vs Diabetes

There have been 21 clinical trials in the past decade drawing a connection between NAC and diabetes.

In a 2012 British clinical study NAC was used to determine if it could increase the levels of depleted intraplatelet glutathione in patients with type 2 diabetes. The conclusion suggested that NAC might help to reduce atherothrombotic risk in type 2 diabetes.

An American user on diabetesdaily.com states the following about NAC:

“Glycine appears to be part of the equation; NAC itself actually raised the blood glucose from the initial fasting value. Once glycine was added at 60 minutes the blood glucose dropped. What I have found, and you of course may be different, is that NAC with glycine drops fasting blood sugar very quickly and the effect remains but decreasing in effect over multiple escalations of blood sugar.”

Vs Cocaine Addiction

Cocaine addicts found it reduced their cravings for the substance and decreased chances of going back on it.

In a Australian small crossover study of 13 participants, designed to determine tolerability and safety, participants (currently abstaining from cocaine use) were given 2400 milligrams of NAC or placebo over 2 days. The NAC group had a significant reduction in cravings, withdrawals and self-reported use compared with baseline, which was not seen in the placebo group. Whereas this study did not aim to investigate efficacy, a signal was found that provided some evidence to justify further research.
[image]
A double-blind placebo-controlled crossover Phase I trial of 13 Americans out of Medical University of South Carolina was conducted to assess the safety and tolerability of N-Acetylcysteine (NAC) in healthy, cocaine-dependent humans. Thirteen participants attended a three-day hospitalization in which they received placebo or NAC. Across placebo and NAC conditions, only mild side effects were noted, and the number of subjects reporting side effects did not differ. There was a trend for a greater reduction in withdrawal symptoms and craving within the NAC condition. These preliminary results suggest that NAC is well tolerated in healthy, cocaine-dependent individuals and may reduce cocaine-related withdrawal symptoms and craving.

So it certainly does not eradicate cocaine dependence but it seems to mitigate relapses and reduce cravings.

A compelling anecdotal report:

A young lady was shaking due to her addiction to crack cocaine. This guy approached her and asked her if she was ok and she lied saying that she was. He knew what was wrong with her because he himself had been addicted to crack before. So he gave her NAC and she felt so good that she decided to keep taking it. He would give her one 600 milligram pill every day for like a week. Then he trusted her enough to give her the entire bottle. And three months later he was happy to see that she got a job and was over her addiction, thanks to NAC!

Vs Smoking Addiction

NAC can also help you quit smoking and feel good without cigarettes as this German on Longecity.com describes:

i remember 10 months ago when i still smoked, and took n-acetylcysteine amino acid, it gave me real happy feelings. but i was totally hypomanic.. now im not if i take those amino acid.. maybe since stopping smoking or it wore off…

In addition to the modulation of glutamate to reduce cravings and reward behaviours, NAC may have a role as an antioxidant in a disorder where oxidative stress is marked. There has been 1 placebo-controlled study investigating 2400 milligrams daily of NAC as a treatment for tobacco cessation. This study recorded participant ratings of use and cravings as well as biochemical measures to confirm reported use. There was no significant difference in the number of cigarettes smoked or carbon monoxide levels between NAC and placebo groups. Treatment adherence and side effects were not reported. The authors noted that alcohol was a significant covariate, and after the removal of 2 outliers based on alcohol consumption and resulting nicotine use, there was only a post hoc trend toward decreased number of cigarettes smoked in the NAC group, and this did not correspond with decreased carbon monoxide levels. Owing to the exclusion of participants from the analysis and the variability of the sample in terms of extraneous factors such as alcohol use, the sample size of this study was too small to make definitive conclusions.

There was another small-scale study that specifically included smokers who were not planning on quitting that investigated biomarkers in smokers after NAC treatment.The outcome of the study was to assess the effects of NAC on the detrimental biophysical aspects of smoking. Participants were randomly assigned to placebo or NAC (1200 milligram daily) groups and treated for 6 months. The study found that in the NAC group, there were decreases in lipophilic DNA adducts between baseline and end point.

In another study nicotine-dependent smokers were treated for 4 weeks with NAC (2400 milligrams daily) to promote cystine-glutamate exchange or placebo. Participants provided weekly ratings of withdrawal symptoms, craving, and carbon monoxide  measurements and logged daily cigarette and alcohol use. The results indicated that the cystine-glutamate exchanger and the glial glutamate transporter were downregulated after nicotine self-administration, and augmenting exchanger activity with NAC reduced the number of cigarettes smoked in nicotine-dependent individuals.

For Cannabis Quitters

In an 8-week double-blind randomized controlled trial of NAC in cannabis- dependent American adolescents, it was reported that participants received NAC or placebo twice a day as well as a contingency management intervention and brief weekly cessation counseling.The conclusion stated there was a positive primary cessation outcome.

“Findings support NAC as a pharmacotherapy to complement psychosocial treatment for cannabis dependence in adolescents.”

In 2016 a clinical trial was conducted in the USA with 89 adolescents about alcohol use while they were taking NAC for marijuana cessation. As a result:

There were no demographic or baseline alcohol use differences between participants randomized to NAC vs. placebo.There was no evidence of compensatory alcohol use during marijuana treatment. In fact, in the NAC group, lower levels of marijuana use were associated with less alcohol use, suggesting NAC effects may generalize to other substances and could be useful in decreasing adolescent alcohol use. NAC trials specifically focused on alcohol-using adolescents are warranted.

The picture coming together from these studies is of NAC as an effective general will power biohack.

NAC can also help people who want to quit smoking marijuana. A Reddit user reports:

I have been using it to stop weed cravings, as I tend to get them pretty bad in the 3-4 days following smoking and I'm trying to keep usage down to only once in a rare while. (not sure if other people have similar problems with using weed once and then wanting to smoke again in the following days). It's been working so far: no cravings to speak of. I've been taking one 1000mg pill a day at the morning with breakfast.

Hangover Biohack

NAC helps your liver do it’s job most effectively by actually preventing the majority of the toxicity that occurs when you drink alcohol. Take 1000 milligrams of NAC before drinking to avoid a hangover.

A Reddit user states that

“Telling people to use NAC after alcohol is dangerous advice, it has to be used before to have a positive effect (~3h before iirc)”

Are you a pescaterian? Taking 500 - 1000 milligrams of NAC to clean up the toxins and heavy metals is a good idea if you’re enjoying seafood. Especially if you’re eating a fish that’s higher up the aquatic food chain. So I’ll have the shark with a side NAC!

Vs Activated Charcoal

Bulletproof® Coconut CharcoalTaking activated charcoal at the same time might decrease the effectiveness of NAC .

An in vitro study was conducted in a University hospital research laboratory in Canada to examine the interaction between NAC and activated charcoal in terms of treating acetaminophen poisoning. The conclusion was that

The presence of N-acetylcysteine reduces the ability of activated charcoal to adsorb acetaminophen and coingestants.

My recommendation, if you want to stack these two hangover biohacks, is to take the NAC several hours before drinking and take the activated charcoal 2-3 hours later at the end of the night.

Some Reddit users shared their personal experiences:

“Yes, I use N-acetylcystine all the time. It's the best thing to take for liver protection. I've used it for years when on nights out drinking. I was actually a groomsman at a wedding this weekend, and was handing NAC capsules out to everyone. Everyone was drinking extreme amounts of alcohol, and were partying till 5am. However, come 10:30am everyone was up for brunch and feeling fine.”;

“I always take my NAC before I go out drinking. Now I have a reason to make sure that always happens. I always knew that NAC could be prooxidant in some situations.”

Vs Smoking Addiction

NAC can also help you quit smoking and feel good without cigarettes.

There has been a placebo-controlled 2014 Medical University of South Carolina study investigating 2400 milligrams daily of NAC as a treatment for tobacco cessation.

  • This study recorded participant ratings of use and cravings as well as biochemical measures to confirm reported use.
  • In addition to the modulation of glutamate to reduce cravings and reward behaviours, NAC may have a role as an antioxidant in a disorder where oxidative stress is marked.
  • There was no significant difference in the number of cigarettes smoked or carbon monoxide levels between NAC and placebo groups.
  • Treatment adherence and side effects were not reported.
  • The authors noted that alcohol was a significant covariate, and after the removal of 2 outliers based on alcohol consumption and resulting nicotine use, there was only a post hoc trend toward decreased number of cigarettes smoked in the NAC group, and this did not correspond with decreased carbon monoxide levels.
  • Owing to the exclusion of participants from the analysis and the variability of the sample in terms of extraneous factors such as alcohol use, the sample size of this study was too small to make definitive conclusions.

There was another small-scale study that specifically included smokers who were not planning on quitting that investigated biomarkers in smokers after NAC treatment.

  • The outcome of the study was to assess the effects of NAC on the detrimental biophysical aspects of smoking. Participants were randomly assigned to placebo or NAC (1200 milligram daily) groups and treated for 6 months.
  • The study found that in the NAC group, there were decreases in lipophilic DNA adducts between baseline and end point.

In another study nicotine-dependent smokers were treated for 4 weeks with N-acetylcysteine (2400 milligrams daily) to promote cystine-glutamate exchange or placebo.

  • Participants provided weekly ratings of withdrawal symptoms, craving, and carbon monoxide (CO) measurements and logged daily cigarette and alcohol use.
  • The results indicated that the cystine-glutamate exchanger and the glial glutamate transporter were downregulated after nicotine self-administration, and augmenting exchanger activity with NAC reduced the number of cigarettes smoked in nicotine-dependent individuals.

A German user on Longecity.com praised NAC's helpfulness in quitting smoking:

i remember 10 months ago when i still smoked, and took n-acetylcysteine amino acid, it gave me real happy feelings. but i was totally hypomanic.. now im not if i take those amino acid.. maybe since stopping smoking or it wore off…

Vs OCD

NAC is known for helping people with OCD; obsessive compulsive disorder.

There was a double blind placebo controlled study conducted in Brazil where NAC was given to adults with treatment-resistant OCD for 16 weeks. The trial did not demonstrate a significant benefit of NAC in reducing OCD severity but a secondary analysis suggested that NAC might have some benefit in reducing anxiety symptoms.

Vs PTSD

Another clinical trial of NAC was in American veterans with post traumatic stress disorder and substance use disorder, who had to receive a double-blind, 8-week course of N-acetylcysteine (2400 milligrams daily) or placebo plus cognitive-behavioral therapy for SUD. The results were in support for the use of NAC combined with psychotherapy.

Fertility

There’s also some good news for those couples who want to conceive.

In 2009 this Turkish studyIn 2009 this Turkish study examined the existence of a beneficial effect of NAC on semen parameters and oxidative/antioxidant status in idiopathic male infertility.

  • The patients were divided randomly into 2 groups. Those in the study group (60 men) were given NAC (600 mg/d orally) for 3 months; the control group (60 men) received a placebo.
  • The results demonstrated that NAC had significant improvements on the volume, motility and viscosity of semen.

Side Effects

  • Very rarely it can cause nausea, vomiting, diarrhea and constipation.
  • Even more rare drowsiness, rashes, low blood pressure and liver problems.

Side effects can be a result of very high doses of NAC, don’t take more than 2400 milligrams daily. Some people experience nausea when taking NAC on an empty stomach, but the majority of people do not experience any side effects if they take it with food.

Here are some anecdotal experiences by users on Longecity.com who have personally felt NAC’s side effects. One Belgian user said:

I tried NAC for about 3 weeks or something, but have stopped because I got really tired because of it. Thankfully after 2 days stopping it I am not tired anymore. Also it made me sleep way longer and also made me feel drowsy when waking up. Another side effect I had is when i took it, afterwards my heartbeat would go from 57 BPM to 90BPM. I could feel my heart beat more and faster, leaving me with an anxious feeling in my chest.

An American complained about unpleasant side effect on skin:

I've been taking NAC for a few weeks in hopes of reducing obsessive skin picking. I haven't noticed an improvement yet. Since starting NAC I have experienced spotting. My period is strictly controlled with birth control pills, so it is quite out of the ordinary. My roommate took it the other day and started her period (off schedule) the same day. I may be a little more relaxed than normal, but more emotionally sensitive. My skin which usually breaks out has been really clear. So obviously this stuff is messing with my hormones.

Apparently different doses can overstimulate different people like this biohacker:

Ive been taking Nac for 2,5 weeks in the morning, strangely i can't tolerate recommended 500mg per day, half of that is ok. With 500mg it feels like its overstimulating, eg. i can't sit normally, feel little restless, the need to move my foot back on worth makes me feel better lol, some nausea too. Little bit of hungry, when i don't eat for an hour it makes my stomach uncomfortable. Even water helps. Go figure, maybe overstimulating my liver. It does reduce my depression and gives me certain energy, so that i don't feel so sleepy during the day. Immune system seems to better too, nose don't drip that much when I'm at home after outdoor activities. Cognitive abilities are somewhat better too, although i feel little emotionless, but sharp. To note out that im not your typical healthy guy either and very sensitive to things like that. No Nac fever or diarreah. After a week i had elbow/upper hand pain for 12h so skipped one day and it went away.

A Canadian an odd effect that NAC had on their eyes:

I tried NAC in late March and threw away the practically full bottle. I too was curious about the things I was reading about NAC, and since I'm in experimentation mode, I purchased some. I was disappointed with the results.
Firstly, the mind-feeling I had was ok, but it was kind of numbing. But the final straw were this eye tremors I started having the second day after taking NAC. I'm particularly sensitive to this since I have a ocular implant in my left eye from a sports injury obtained nearly 20 years ago. I experienced bad tremors in my right (good eye), and I've never experienced this with any other supplement. After 2 days of this, I stopped the NAC since I suspected it was stripping (binding) my retina of zinc which the eye needed - the chelation effect. After a couple weeks I decided to try 1 500milligram capsule of NAC and the eye tremors started again a couple hours later.

A Redditor noted some other interesting side effects:

I've been taking this supplement for three weeks and while I have had noticeable results with lessening morning OCD/rumination, I've also gained a bunch of weight....almost 7lbs.

Cofactors

NAC could obviously be combined with other nootropics and vitamins which people do to enhance its effects. Here are some anecdotal experiences by Biohackers online:

This neurotic Redditor describes a stack for mitigating rumination:

I take 4.8g NAC/day in divided doses. It changes chaotic mind to not-giving-a-fuck mind if that makes sense. Things that were previously significant are less significant and the amount of craziness (neuroticism) I experience seems to be less. I can focus and enjoy my job instead of thinking about how I and my parents are going to die or the lack of meaning in life or the cruelty of life; etc. It helps me ruminate a lot less on existential issues and just cope with life. I now combine it with sarcosine, piracetam, and tianeptine. I haven't done much reading on interactions between those but sometimes I vape nicotine alongside all this and I feel great. It puts my obsessive rumination about things I can't control to bed.

This user here uses another nootropic to boost his experience:

Well, I've been consistently dosing 20mg of noopept twice daily, and 600mg of NAC three times daily. I haven't had any negative effects. The positive effects are subtle, now that I've been doing it for so long. I take a couple days off a week, and notice a much clearer mind once I return to it.

This Belgian combines NAC with other supplements to alleviate his symptoms:

After being supplement free for a while i restarted nac yesterday; so far it seems to immensively help with "motivational thinking" not in the way of doing tasks but in the way of avoiding things like being junkfood when out when i should save the money;.I also take 4 gram of phenibut a day (this should be avoided for most as its physically addictive) and use stimulants for my ADHD; anhedonia and social anxiety.

This New Yorker takes NAC with a lot of other supplements and vitamins in order to combat neurotoxicity:

In the morning, I'll take NAC and mitochondrial support in the form of Ubiquinol, PQQ & Astaxanthin. I'll also take creatine, for the sake of reducing glutamate toxicity. I take antioxidants (A, C, E, D, K), along with DHA/EPA & krill oil, to strengthen my defenses against ROS & RNS.

Risk Grade: B

  • Not recommended for people who have a genetic condition called cysteneria.

Conclusion...

N ACETYL L CYSTEINE NAC CAPSULESShould otherwise healthy people (or Biohackers) supplement NAC?

In my opinion totally healthy people could also use NAC especially when they are about to drink a lot, like for example, before they go to a party or just hang out with friends because one of its main functions is to protect against liver damage.

It indeed demonstrates many other health benefits and has been shown to help prevent multiple forms of cancer through a few different mechanisms:

  • NAC as a supplement has many uses and can help people with a diverse set of issues, including mental health disorders like OCD, Autism, PTSD, etc, addiction issues, infections, inflammations and in states of oxidative stress.
  • It boosts production of glutathione and plays a role in detoxification of heavy metals out of the body.
  • NAC is commonly used for liver support but people often take it to treat bronchitis, relieve hangover symptoms, increase immunity against certain strains of flu, improve insulin resistance and thereby help improve diabetes, and hypoglycemia.

NAC is the super antioxidant, nootropic and nutrient with a wide range of health benefits has been shown from many different studies.

Nootropic Ingredients

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