Our 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 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?
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
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.
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.