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My experience supplementing with NAC: benefits, side effects, potential risks

NAC benefits

Let’s start with an attention grabbing fact about NAC.

N-Acetylcysteine, or NAC for short, is one of a handful of dietary supplements that is also used quite frequently in hospital settings.

That’s right, when a patient comes to the hospital with an acetaminophen overdose, standard of care is to use intravenous NAC to protect the liver and help the body excrete accumulated toxins. 1 This is one of NAC’s primary benefits – the ability to replenish levels of glutathione (one of the body’s most important antioxidants) in the liver.


When we take acetaminophen, a metabolite called NAPQI is produced, which in high enough doses is very toxic to the liver.1 Under normal circumstances, one of the body’s most important “endogenous” antioxidants, glutathione, cleans up this mess before any lasting harm can be done. However, when mega doses of acetaminophen are taken, hepatic glutathione stores (glutathione in the liver) run out and the body doesn’t have enough to detoxify the bad stuff the acetaminophen is producing.

The result can be liver damage and, if enough is taken, death.

Enter NAC, which is a glutathione precursor and proven nutrient for restoring depleted glutathione levels. A double blind, placebo control study showed a 28% reduction in mortality when IV NAC was administered after an acetaminophen overdose.2

I list NAC as one of my supplements to take to avoid a hangover because drinking alcohol also draws down glutathione stores and taking NAC is one of the most effective ways to build the glutathione back up.

So, we’ve already learned two important things about NAC:

  1. It’s a glutathione precursor and can increase levels of glutathione in the liver after depletion (but not when glutathione levels are already normal, so it’s not going to “supercharge” your glutathione levels)
  2. It’s one of the few supplements used in clinical settings (kind of like S. Boulardii with antibiotic associated diarrhea)

While I cycle NAC on and off, and most certainly don’t take it everyday for months at a time, it’s one of the supplements I “believe in,” which is a short list these days.

Evidence Based Benefits of NAC

What are some of the other proven benefits of NAC?

NAC can improve mood

For me, one of the pleasant surprises of supplementing with NAC is improved mood.

Now, I don’t want to overstate things. Just as Dan Harris titled his meditation app “10% happier,” and not “holy crap, meditation has made me into a different person and I never ever have anxiety now,” the impact of NAC on my mood has been subtle, but also real and tangible.

I feel an enhanced sense of calm and focus and notice additional resiliency to work stress. During the past week, I’ve also found that NAC is in the class of supplements that gives me a social boost.  With 500mg of NAC in my system, I was a touch more outgoing and likely to engage with waiters, people around the city, and more upbeat in general. If I were to quantify, I’d say the difference is in the 10-15% range.

It seems my observations about NAC benefitting health by boosting mood have been demonstrated in clinical studies.

Double blind, placebo controlled studies have shown promise for the ability of NAC to help alleviate depressive disorders. In fact, while not all the studies have shown efficacy, I was particularly impressed by this meta analysis of 5 studies which found NAC has value in treating depression. 3 Keep in mind that the meta analysis started with 38 studies and had to throw out 33 of them for failure to meet “inclusion criteria,” which I take as a message that many of the NAC studies out there could be less than reputable.

NAC improves mental health

The likely mechanism here is NAC appears to work as a glutamate antagonist. 4

For those of you who have regularly read the blog, you’ll remember glutamate is the “gas pedal” neurotransmitter, which is great, unless pressing on the gas has you accelerating through a brick wall.

An excess of glutamate can lead to anxiety, as well as excitotoxicity, which some theorize is the cause of many neurodegenerative disorders. 56

Another calming amino acid, L-theanine, is also a glutamate antagonist.

NAC is actually quite popular in the field of psychiatry and medical literature documents NAC experiments to treat everything from OCD, to addiction, to Bipolar disorder. 4

May reduce prevent addiction relapse

Some studies have looked at NAC’s ability to help in the addiction recovery and healing process. In one study, 7 administering a 2,400 mg dose of NAC (a very high dose) to patients suffering from cocaine addiction normalized glutamate levels, which study authors credited for a reduction in impulsivity that could lead to further drug use. Interestingly, healthy controls saw no difference in their glutamate levels. Since elevated glutamate levels are linked to relapse, study authors were encouraged by the findings.

NAC and the lungs

NAC is an anti-mucous agent, and many people take it for conditions like COPD, which involves the unpleasant build up of mucus in the lungs.9 The idea is that NAC can help alleviate an increase of oxidative stress and inflammation in the lungs, but it’s also important to be aware that there are studies on the other side of the divide as well. Just as eating animal protein rich in pro growth amino acids, like the BCAAs, can speed cell growth, both good and bad, there is emerging evidence that antioxidant supplements have the potential to protect both good and bad cells as well.

A study in mice found that NAC supplements could accelerate tumor growth in the lungs. The takeaway for the authors was that NAC could actually be dangerous in high risk populations, such as those struggling with COPD.10

NAC Side Effects

NAC and Sulfur Sensitivity

I’ve written before about the CBS family of genes and how certain SNPs in those pathways can affect sulfur metabolism. One SNP, CBS C699T, is associated with an up-regulation of sulfur metabolism, which can lead to higher levels of ammonia in the blood as well as gastrointestinal symptoms.

Side note, SNPs in the urea cycle can have the same result.

What does this have to do with NAC?

NAC, alpha lipoic acid, and glutathione are all “sulfur donor supplements,” meaning their building blocks are sulfur containing amino acids.11 In individuals whose bodies use up these amino acids too rapidly, as is the case when certain CBS variants are present, sulfur sensitivity can occur. As such, and with 28% of the population carrying at least one copy of the CBS C699T SNP, some people will have reactivity to NAC and the sulfur family of supplements.

My Experience With NAC

I’m writing this review after taking a 500 mg dose of NAC every day for a week. As I’ve made clear in my recent post Are Your Supplements Making You Sick? I tend to cycle on and off virtually every supplement I take. It’s rare that I take any supplement for longer than a few weeks without some time off. Just the way I do it with supplements.

Previously, I’d taken NAC as a one off supplement a few hours before consuming alcohol, and experienced no side effects, but after a week of steady use, the main side effect I experienced was stomach upset and, unfortunately, diarrhea. On the 7th day of dosing at 500mg, I developed heart burn (in retrospect it may not have been wise to take NAC on a breakfast of just scrambled eggs) and eventually what some in the MCT oil world call “disaster pants.” The long and the short of it is that the acidity of NAC really upset my stomach after a somewhat prolonged period of usage. The fact that I developed stomach sensitivity after a week at a 500mg daily dose made me marvel at some of the psychiatric trials using doses 4 times this large.

I do plan to take NAC in the future, but when I do, I think I will either split the 500mg dose into two pills, and perhaps even cut it with an alkalizing agent like potassium citrate. Taking NAC with a proper full meal will also be a priority.

John O'Connor

John O'Connor is the founder of Gene Food, a nutrigenomic startup helping people all over the world personalize nutrition. John is the host of the Gene Food Podcast and a health coach trained at Duke's Integrative Medicine Program. Read his full bio here.

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  1. Rudy says:

    Hello, thank you so much for the review. pretty informative.
    But I’m a bit concerned about the study in mice that found that NAC supplements could accelerate tumor growth in the lungs.
    I take 1200mg of NAC per day, it helps my OCD, helps me stop ruminating.
    I’m 23, and healthy.
    do you think I should be concerned?

  2. Kelly says:

    “CBS C699T, is associated with an up-regulation of sulfur metabolism.”

    What is this, 2007? The ‘CBS upregulation’ hypothesis — and that’s all it was — has been discredited for at least 8-10 years. There is absolutely no research or clinical evidence to back up ol’ Yasko’s claims. Even Ben Lynch dropped that malarkey at least five years ago.

  3. Amber says:

    Everyone is different, i take it on a completely empty stomach, I read it works better that way, and Ive had no issues, I also take a much higher dose than 500mg.
    You didnt really mention any positive side effects for yourself other than the hangover issue.
    Makes me wonder if you could really benefit from just taking it for a week.
    It took weeks of it being in my system before I saw any positive results.

  4. Isabel says:

    Good Article, I have learned to take NAC not with a meal, only with a small bite of toast or something. Especially not with protein. Maybe that’s why your stomach was upset.

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