All About NAC: Supplement Benefits, Side Effects, Dosages

nac benefitsOur understanding of how antioxidant supplementation works has changed in the last decade. Rather than act directly as antioxidants, most of these compounds stimulate the body’s own production of endogenous antioxidants. That’s right—most of the popular and beneficial “antioxidant” supplements work by provoking a mild hormetic stress response that activates our own antioxidant defenses.

But homegrown antioxidants aren’t made out of thin air. They are material substances that require physical building-blocks. Probably the most important antioxidant is glutathione, and its most important building block is NAC.

What is NAC?

N-acetyl-cysteine, or NAC, is the stable, supplement form of the amino acid cysteine. Cysteine provides one of the most crucial backbones undergirding the body’s premier antioxidant: Glutathione.

In the conventional medical world, NAC is mainly used to rescue people from acetaminophen toxicity. If you overdose on Tylenol and get to a doctor within 8 hours, they’ll give you a big dose of NAC to save your liver and your life. But how does it work? How does NAC beat Tylenol toxicity?

By increasing glutathione stores in the liver. Glutathione binds to the toxic Tylenol metabolite and makes it harmless, but it doesn’t last forever. A big dose of a major toxin like Tylenol is enough to deplete glutathione stores and increase acute glutathione requirements. NAC provides the raw material for glutathione production, allowing it to commence and get to protecting.

Might this have other effects? Does glutathione do anything else?

It reduces reactive oxygen species down to less damaging metabolites.

It is the master detoxifier, a major line of defense against invading mutagenic, carcinogenic, and inflammatory agents.

It defends against glycation.

It controls hundreds of proteins in the body.


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It protects against lung damage and maintains respiratory function, especially in the context of infectious respiratory diseases.1

It regulates glutamate levels in the brain, reducing over-excitation.

In other words, it does a lot. We should probably try to keep our levels up. If we don’t?

Well…

Low levels of glutathione have been linked to such disparate conditions as diabetes, tuberculosis, cancer, HIV, and aging.2 Heart failure patients tend to have low glutathione.3 Low glutathione levels are generally associated with elevated markers of inflammation, like CRP.

Okay, so glutathione is important, low levels are linked to many different diseases and health conditions, it’s a good idea to have adequate levels for general health, and NAC is one of the better ways to replenish glutathione.4 At normal doses of Tylenol, taking NAC along with it prevents glutathione depletion without negatively affecting the therapeutic effect of the drug.5

NAC helps the liver metabolize alcohol, too, by speeding up the clearance of its most toxic metabolite—acetaldehyde. In rats, NAC even mitigates the hypertensive effect of drinking alcohol, suggesting general detoxification effects.6

Detoxification with NAC

All those “experts” who say detox is a myth and your body is perfectly able to detoxify everything it needs to without fancy supplements and therapies are half-right. The body is able to detoxify a wide range of toxins, provided we give it the substrates it requires. NAC is one such substrate that seems to help us deal with incoming toxins.

In workers with chronic lead exposure, NAC increases antioxidant capacity in red blood cells, reduces oxidative stress, and lowers blood levels of lead.7

In adults with acute pesticide poisoning, NAC (600 mg 3 times per day) reduces inflammatory markers and the need for atropine (a pharmaceutical that treats pesticide poisoning).8

After exposure to diesel fumes, taking NAC reduces blood vessel damage and, in asthmatic patients, lowers the airway responsiveness.910

NAC even reduces the toxic effects in people who eat poison mushrooms or get dosed with mustard gas.1112

If large doses of NAC can help people deal with serious toxin loads, moderate doses of NAC can probably help people deal with normal loads.

NAC and Lung Health

In bronchitis and Chronic Pulmonary Obstructive Disease (COPD), the lungs lose glutathione and accumulate too much thick mucus, reducing their function and making it harder to breathe. When you take NAC in this situation, it replenishes lung glutathione and thins out the mucus.

The result is that bronchitis patients who take NAC over the course of 3-6 months experience lower rates of “exacerbations” (worsening episodes) and see their symptoms improve.13 Same goes for COPD patients on a year-long course of NAC; they enjoy improved lung capacity.14

Flu Resistance

One study in older adults had some remarkable results.15 Subjects were randomized to one of two groups. The first group got placebo. The second group got 600 mg of NAC, twice a day, for 6 months. Over the course of the study, they tracked “influenza-like” symptoms, finding that the NAC group had far fewer than the placebo group. Then they tested the subjects for influenza antibodies and found that both groups had equal seroconversion rates. Both groups were equally likely to have gotten the flu over the 6 months, but just 25% of the infected NAC group ever showed symptoms versus 79% of the infected placebo group who showed symptoms.

NAC Reduces Inflammation and Oxidative Stress

The modern world is a stressful place. We have long commutes to jobs we often dislike. We’re stuck indoors when we’d rather be outside in the fresh air and sunlight. We have to closely read labels—or avoid them altogether—to make sure we’re eating healthy fare. The air is polluted, we’re disconnected from nature, we sit too much and move too little. I’m not saying this to be a downer or alarmist—the world remains a beautiful place full of joy and wonder—but a realist. Life is good but our bodies are under constant, chronic low-level assault from evolutionarily novel physiological and psychological stressors.

Increased oxidative stress is the baseline for too many people, and NAC has been shown to be one of the best “all-purpose” supplements for reducing it.16

Mental and Psychological Health

NAC checks off a few important boxes for mental health. It crosses the blood brain barrier, reduces oxidative stress, and regulates glutamate levels in the brain. Now, glutamate isn’t “bad,” but too much glutamate in the wrong places can lead to over-excitation. That’s often what we see in mental and psychological disorders—over-excitation, excessive activity.

NAC smoothes that out. It sticks glutamate where it belongs in the right concentrations. It provides the right amount of inhibition to counter the excitation.17

This is probably why NAC supplementation has shown preliminary promise in treating a number of disorders, including autism, Alzheimer’s disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, anxiety, attention deficit hyperactivity disorder and even mild traumatic brain injury.18

NAC and Fertility

Both male and female infertility often come down to elevated oxidative stress. Can NAC reduce stress? Yes. Can NAC improve fertility? Yes.

In men visiting a fertility clinic, an NAC supplement (600 mg/day for 3 months) increased serum antioxidant capacity, reduced oxidative stress, and improved sperm quality, motility, and consistency.19

A combo of selenium and NAC was also able to improve semen quality in men with fertility issues.20

As for women’s fertility, NAC seems to be most effective in women with PCOS already taking clomiphene citrate (a PCOS drug meant to stimulate fertility). A pair of studies found that NAC increased both ovulation and pregnancy rate in women with PCOS who had proven resistant to clomiphene citrate alone.2122

Should Everyone Take NAC?

Not necessarily. Most of its benefits occur in people with depleted glutathione levels and/or elevated inflammatory status.

One paper found that NAC was only helpful in patients with depleted glutathione levels.23 Those with low glutathione saw platelet function improvements, while those patients with normal glutathione levels saw no improvements in their platelet function.

Another paper found similar results with depression. Only those patients with elevated CRP levels at baseline experienced a reduction in depressive symptoms after taking NAC.24

And most of the studied health conditions are quite serious and, relatively speaking, rare. What draws me in is the fact that glutathione is upstream of so many different physiological processes. It’s not some specific compound with very limited application or relevance. It’s a specific compound with broad applications.

You may not have the glutamate over-excitation issues of someone with full-blown schizophrenia or social anxiety disorder, but a little NAC might help you focus or improve your internal self-talk.

You may not have COPD, but making sure your lung glutathione stores are replete isn’t a bad idea.

You’re probably not completely infertile, but reducing oxidative stress and improving sperm or endometrial quality never hurt anyone’s chances.

All that said, NAC is one of the safer supplements available. It probably won’t hurt to try a small dose whether you have elevated inflammation or depleted glutathione or not—and many people do have suboptimal glutathione status without knowing it.

What’s a Good NAC Dosage?

Many of the therapeutic effects used in the studies I referenced today were in the 500-600 mg range. Sometimes higher, but not necessarily.

I included 500 mg of it in my broad-spectrum micronutrient supplement, Primal Master Formula, because that is a well-tolerated, well-attested dose that’s safe to use and quite effective at glutathione maintenance.

I am a very light/moderate drinker these days, but whenever I do have more than usual, I’ll take 500 mg of NAC and 500 mg of vitamin C about an hour before drinking. This dose seems to improve the positive effects and reduce any negative side effects, probably by increasing glutathione, enhancing ethanol metabolism, and clearing acetaldehyde more quickly.

That’s it for NAC, folks. If you have any questions or comments, drop them down below.

TAGS:  supplements

About the Author

Mark Sisson is the founder of Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and the New York Times bestselling author of The Keto Reset Diet. His latest book is Keto for Life, where he discusses how he combines the keto diet with a Primal lifestyle for optimal health and longevity. Mark is the author of numerous other books as well, including The Primal Blueprint, which was credited with turbocharging the growth of the primal/paleo movement back in 2009. After spending three decades researching and educating folks on why food is the key component to achieving and maintaining optimal wellness, Mark launched Primal Kitchen, a real-food company that creates Primal/paleo, keto, and Whole30-friendly kitchen staples.

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49 thoughts on “All About NAC: Supplement Benefits, Side Effects, Dosages”

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  1. Thanks for talking about NAC! I do pulmonary medicine and my patients with COPD/chronic bronchitis who take NAC (it’s OTC and many aren’t willing to pay for it) seem to do quite well and report less exacerbations.

    Personally, I’ve supplemented with it and didn’t notice much difference. I suppose when living a primal lifestyle, my body is likely not glutathione depleted. I’ve reserved its use, similar to you, if I decide to indulge in some alcoholic beverages to help curb the effects.

  2. Most of your reasons for taking NAC is to boost glutathione. Given that newer studies show that glutathione is bioavailable, why do you recomend NAC over glutathione?

    1. I’m assuming it’s because supplemental glutathione is expensive $60-70 for a 1 month supply where as NAC is half that price for a 2-3 month supply. Why take glutathione directly when you can help your body produce it’s own for a fraction of the price. Just my guess.

  3. Curious if you had any research on the risks/benefits of supplementing with Liposomal Glutathione?

  4. Very interesting study on flu resistance in older adults. NAC might be worth a try as a preventative seasonal measure.

  5. I typically don’t use supplements. Are there any good whole food sources of NAC or glutathione?

    1. Yes, rather than use a supplement I just use pure unflavoured, un-denatured whey protein which I believe is one of the highest natural sources of cysteine, plus many other benefits too. Mark also sells the Primal Fuel whey protein which is great if you want a bit more flavour…

    2. The best dietary sources of glutathione are porcini mushrooms & asparagus.

        1. Just make sure to avoid overcooking them as glutathione concentrations are somewhat sensitive to cooking durations.

  6. Hey Mark!

    Great Post! I had no idea that NAC can affect so many parts of your health.

    I have a question though. What are some of the major side effects of NAC supplements and is there any specific brand you would recommend?

    1. Not good for those with mercury toxicity. Yes, the massive glutathione boost will chelate the mercury, but too fast. Better to do that slow and steady and with binders, otherwise you cause redistribution and feel a whole lot worse. Dizziness is a symptom of this.

      1. Totally off-topic, but: Was just reading this article, and caught this comment/name- by any chance are you the Elisa from Seattle? (I remembered us both talking about Mark Sisson when i was there). If so, this’s Jeff, from airbnb. Cheers to you guys!

  7. Thanks for your article on this fabulous supplement. Years ago I read an article on it and thought we’d give it a try. My husband, who isn’t really into taking supplements, gave it a try along with Vitamin D with K2, Maca. He noticed an improvement all around and if we don’t take them for a few days he can tell right away. We work at stressful jobs so it’s really helpful to both of us, although I’m off work presently since I’m 65+ and get to stay home with pay (yay). I didn’t know about the benefits for the liver, I will make sure I take it if I drink wine now.

  8. Hi “Mark” Sir…..All my confusions have gone away. I am so benefited by visiting your site. Thanks sir share this information.He has really sweet responses to basically all of these..

  9. I have read that you are supposed to take NAC away from glycine, or the benefits of both are negated. Is this correct?

  10. You mention side effects in the title of the article and refer to mitigation of said side effects but then don’t list any.

  11. Most of the reasons you take NAC are for improving glutathione. Since more recent studies indicate that glutathione is bioavailable, why do you suggest glutathione to NAC?

  12. Taking something that disrupts the mucous lining/biofilm of the gastrointestinal tract chronically likely invites dysbiosis, SIBO, and intestinal inflammation….

    What would you say about that?

  13. There was this mouse study where NAC supplementation increased lung cancer, so there’s that.

    Also, not a very friendly supplement for digestive issues.

    I wouldn.t take it chronically.

    1. Something I’ve always been a little unclear on, is it safe to use N-Acetyl Cysteine the morning after drinking for hangover help? I know that its advised not to take NAC after drinking because it can actually exacerbate liver damage. Then how long after should one avoid dosing? Is the next morning okay?
      A study that showed aggravated liver damage from both was when nac was administered four hours after ethanol ingestion.

      So, while I do take NAC(and Mg, B, ALA) prior to drinking, I personally avoid nac until the hangover has passed. They appear to have a pro-oxidant effect together, though its hard to tell if it is ethanol itself or the metabolites that synergize negatively with nac.

  14. Frustrated. Whats in your Primal formula? How many a day do you need to take?

  15. I have taken NAC for over 20 years due to elevated inflammatory markers of unclear etiology. I also take relatively high dose omega 3 and a polyphenol supplement and my markers remain in the normal age. At age 72 I seem to be doing fairly well.

  16. NAC is also one of the only treatments for compulsive hair-pulling

  17. Mark,
    We are up here in Canada love you plain and simple! I am the youngest of five my brothers and I enjoy your posts and I wanna continue our quest to master primal living. My brother George has been able to lose 50 pounds and keep it off I need to lose 80 and continue to try low carb. We look forward to the day we can get all your products in Canada it is frustrating not being able to order them.

    I just wanted you to know how much you are appreciated and we are grateful for you and everything that you continue to do for us and humanity as a whole.

    Stay safe,
    Cathy aka Wildwoman

  18. NAC sounds like a great supplement. I have stage 2 liver disease from taking drugs over the last 15 years to combat my psoriasis and psoriatic arthritis. So, I obviously have an auto immune disease, like so many other people. Do you think this would be a good supplement for me to take? I guess I would like to see a list of contraindications…

  19. I read that that our NAC (or is glutathione) levels drop as we age and by the time we’re 80 we don’t produce any. Have you read anything to substantiate this? Also, when you take NAC alone do you use another brand? Quicksilver has a liposomal variety that is very pricey and Elysium has a lot of hype about theirs (also very pricey).

  20. I used to hear that taking NAC was better than taking straight glutathione.

    I’ve since heard that if we take NAC it can convert to glutathione or it can convert to an undesirable compound (I can’t remember what now) and there is no way to really know which is happening in your body, so it’s better to take liposomal glutathione.

    I think the person saying this is Dr Ben Lynch (Dirty Genes) who makes sense to me from a science perspective, but during Covid seems to have become a bit of a conspiracy theorist (AND sells liposomal glutathione) so I don’t know what to think!
    I’d love Mark’s or others’ opinions.

  21. Should we just take glutathione instead?
    What should be the right dosage?
    Thanks

  22. Hi Mark,

    What do you think about lipismol glutathione? Would NAC be better?

    Regards Clara

    1. Per my husband, who is a general surgeon working in a hospital, NAC is being given as a supplement to many Covid19 patients with very positive results. It seems to help the immune system mount a defense to the virus, and it thins the thick secretions that Covid patients have trouble clearing from the lungs. Hopefully there will be more research on NAC usage with Covid19 patients.

  23. I read the article, then I read the comments, and now I’m totally confused ?????

  24. My mother has COPD and my husband works in the trucking industry …

    I’m thinking I should buy in bulk ?

  25. I do have a question. Why not just take glutathione supplements directly? I have been doing that for over a year.

  26. I take NAC but I also take s-acetyl glutathione. What is your opinion on this type of glutathione that is supposed to be highly bioavailable?

  27. Hi Mark: I try to read everything you send out.
    and I could drink the sesame/ginger dressing straight.
    question-I have immunosuppression resulting from high
    mycotoxin level. (working on it).
    I am VERY intolerant of methylfolate, glutathione in any form and
    even NAC gives me trouble. my levels are low and at age 65 my Doc thinks I
    would not survive a cytokine storm.
    would PQQ be a good substitute for glutathione?
    and why can’t i tolerate it?!
    THANK YOU.
    Lynda Gordon

  28. Hey Mark sir
    Enjoyed reading the article above, really explains everything in detail.
    I always prefer to read the quality content and this thing I found in you post.
    I have been searching for such an informative post for many days.
    Thank you and good luck in the upcoming articles.

  29. Very interesting study on flu resistance in older adults. NAC might be worth a try as a preventative seasonal measure.

  30. nice post about NAC: Supplement Benefits, Side Effects, i just read this post and i grab lots of knowledge. Thank you.