N-acetylcysteine may be the most potent and healing supplement that most people have never heard of. It can be life changing. When people do hear about it, they wonder exactly what it is and whether they should take it, so with that in mind here’s a guide to n-acetylcysteine.
There’s nothing mysterious about n-acetylcysteine (NAC), which can be purchased over-the-counter and is inexpensive. NAC is sometimes known as a pro-drug, meaning that it becomes something else inside the body, and that something else is what exerts its physiological effect.
Pro-drug itself is a misnomer, however, since what NAC becomes is the amino acid cysteine, which is an essential amino acid, a required nutrient. (Cysteine is sometimes termed “conditionally essential”, since the body can make it from another amino acid, methionine, but not always in sufficient quantities.)
Amino acids, of which cysteine is one, are the constituents of proteins, which are in turn components of virtually all foods, and are found in large amounts especially in animal products such as meat, eggs, and dairy.
When NAC is ingested, cells take it up rapidly, the acetyl group is removed, and the active ingredient, cysteine, remains.
Why wouldn’t you just take cysteine?
The reason is that cysteine is a sulfur amino acid, and is easily oxidized, which makes taking it as a supplement non-optimal. By adding the acetyl group to cysteine, the molecule becomes much more stable, storable, and suitable for use as a supplement.
Why would someone need more cysteine? The answer lies in the molecule glutathione.
Everyone has heard of antioxidants, supposedly healthy molecules in food that capture free radicals inside cells, detoxify them, and prevent oxidative damage.
Controlling free radicals is indeed important, and therefore the body has not left this to the chance ingestion of certain foods, but has its own antioxidant system. The system includes enzymes such as catalase and superoxide dismutase, and the small molecule, glutathione.
Glutathione is the most abundant — and therefore, important — component of the body’s antioxidant system.
Glutathione is composed of three amino acids, glycine, glutamine, and cysteine. Of these three, glycine and glutamine are non-essential amino acids made by the body, and are usually not in short supply. Cysteine, however, may not always be available and has therefore been termed the “rate-limiting” amino acid in glutathione synthesis.
In simple terms, not enough cysteine, then not enough glutathione.
Levels of glutathione fluctuate in health, disease, and aging. Glutathione is used up when it detoxifies free radicals and must be replaced or recycled.
When large enough amounts of free radicals occur under stressful conditions and over power the internal antioxidant system’s capacity, glutathione is depleted and a state of oxidative stress exists. These stressful conditions include infection, diabetes, cancer, aging, and even exercise.
By supplying cysteine in the form of NAC, glutathione is replenished and oxidative stress is reduced or eliminated. That’s the source of the health benefits of NAC.
The glutathione system is considered a target of therapy in a number of neuroimmune disorders, including depression and chronic fatigue.
Oxidative stress also causes disruption of important hormonal and other cellular signals, since these signals depend on molecular shape and interaction, and these in turn depend on pH and the redox status of the cellular milieu. So, the body does not function optimally in oxidative stress.
NAC replenishes glutathione, including in the brain, and this is likely its mechanism of action in various psychiatric illnesses.
Bipolar depression: An open-label trial of NAC in patients with bipolar depression yielded “a robust decrement in depression scores”. The patients took 1 gram NAC, twice a day, and this was as “a maintenance treatment for bipolar disorder.”
Addiction: NAC has been studied for its effects in cocaine, marijuana, and nicotine addiction, with varying success, and studies are ongoing.
OCD, Pathological Gambling, Trichillotomania (pathological hair pulling): NAC has been studied in all of these, on the whole with good results.
Autism: A small randomized controlled trial found that irritability in autism patients was significantly improved with NAC.
NAC may be useful in treating chronic fatigue.
In chronic fatigue, oxidative damage to DNA is higher than in controls, which indicates that oxidative stress exists in that condition. It’s been speculated that competition between the immune system and muscle for glutathione precursors such as cysteine favors the immune system. When that happens, muscles become depleted of glutathione and cannot function properly, leading to fatigue and myalgia.
A number of studies have found depleted levels of glutathione in chronic fatigue syndrome, and n-acetylcysteine results in improvement of symptoms.
Michael Maes, the biological psychiatrist who’s done massive amounts of research on chronic fatigue, found that normalization of leaky gut in chronic fatigue patients resulted in clinical improvement. (In my own journey through chronic fatigue syndrome, finding this paper was like finding the Holy Grail.) Among the supplements that Maes says improve gut barrier function are glutamine, zinc, and n-acetylcysteine.
I used n-acetylcysteine as part of my program to overcome chronic fatigue, and wrote about in my book on that topic.
One of the more remarkable studies on NAC has been in the prevention of influenza. A total of 262 people, 78% of them >65 years old, and 62% of them suffering from a chronic illness, were randomized to 600 mg NAC twice a day for 6 months, or placebo. Frequency of seroconversion, that is, the development of antibodies to a particular strain of flu virus, was about the same in either NAC or placebo groups.
But only 25% of the NAC group who were infected developed symptoms, as opposed to 79% of the placebo group. NAC effectively prevents the flu, or this particular version of it anyway.
NAC prevents the replication of the flu virus in cell culture.
Would this work with other viral illnesses, such as the common cold? Well, in people with chronic bronchitis, NAC dramatically reduced the number of sick days, by about two thirds.
HIV infection is associated with a massive loss of sulfur. Cysteine, which is a constituent of glutathione and which NAC supplies, is a sulfur amino acid, so loss of sulfur means glutathione depletion. The average sulfur loss of asymptomatic patients was equivalent to 10 grams of cysteine daily — truly massive. If extrapolated, that amounts to 2 kg cysteine a year. The implication is that they might be asymptomatic until glutathione is heavily depleted, and then become symptomatic.
In people with human immunodeficiency virus, low glutathione levels are associated with decreased survival. NAC can help:
…oral administration of the GSH [glutathione] prodrug N-acetylcysteine replenishes GSH in these subjects and suggesting that N-acetylcysteine administration can improve their survival, establishes GSH deficiency as a key determinant of survival in HIV disease. Further, it argues strongly that the unnecessary or excessive use of acetaminophen, alcohol, or other drugs known to deplete GSH should be avoided by HIV-infected individuals.
An open-label trial found that NAC significantly increased glutathione up to a level 88% that of uninfected controls.
At one time there was great interest in using NAC for treating or supplementing HIV positive people, but as far as I can tell, that interest has waned, possibly because of more effective treatments or a relative lack of efficacy of NAC.
One effect of NAC is an increase in fluidity of mucus, and therefore it’s been tried in lung diseases.
High dose NAC modulates inflammation in cystic fibrosis. The high dose was 0.6 to 1.0 g, three times daily, for 4 weeks. “This treatment was safe and markedly decreased sputum elastase activity (P = 0.006), the strongest predictor of CF pulmonary function.”
In chronic obstructive pulmonary disease (COPD), 600 mg of NAC daily greatly lowered the rate of exacerbations of the illness and dramatically lowered number of sick days.
Interestingly, NAC can increase time to fatigue in endurance exercise. In cyclists who took 1200 mg daily of NAC for 9 days, sprint performance time was improved and oxidative damage was decreased.
Taken just before a bout of exercise, 1800 mg NAC reduces muscle fatigue. NAC increases fat oxidation during exercise and lowers lactate levels.
Why not take NAC all the time so that, if you train hard, you can get these benefits? I suspect that NAC could function as an antioxidant, and prevent the health-promoting effects of exercise. However, taking NAC after exercise could promote better recovery, since exercise depletes glutathione.
In general, though, the damage caused by exercise is part and parcel of its effect on improving performance and health. Whether NAC ultimately improves or decreases exercise performance over the long run remains unknown, as far as I know. I note that NAC is not a banned substance in sports, so if it worked as well as suggested, it seems that it would be. On the other hand, it may not be banned because it would be all but undetectable a few hours after taking it, so why bother banning it.
Aging has been characterized as a cysteine-deficiency syndrome. Oxidative stress, and consequent lower glutathione levels, affect each other in a vicious cycle. Inflammation increases, and autophagy decreases.
A double-blind study in frail elderly people found that NAC doubled leg extension strength during a 6-week exercise program, and those taking placebo had zero increase in strength. Impressive. TNF-alpha, an inflammatory cytokine, decreased. Based on this, NAC could be quite useful in the frail elderly to help get them less frail and improve their quality of life.
NAC could decrease fat mass and increase muscle mass in the elderly too. (Would it do the same for bodybuilders? I don’t know, but I suspect what’s going on is that inflammation is decreased, causing the changes in body composition. A young, healthy bodybuilder might not be able to make use of it in that regard.)
NAC can also improve immune function and possibly ameliorate cachexia.
NAC can increase the lifespan of fruit flies up to 26%. To my knowledge, this is the only species of animal in which NAC has that effect.
“NAC is safe and well tolerated when administered orally but has documented risks with intravenous administration.” (NAC is administered IV in cases of acetaminophen overdose, one of the few indications for which NAC is used in mainstream medicine. It works too, saves people from liver transplants via repletion of glutathione.)
The doses used in the studies I’ve cited are all over the place. Some used 600 mg every other day, some used 600 mg three times a day, and some of the HIV patients were taking it in several gram amounts daily. The suggested dose on the bottle of NAC I have at home (NOW brand) is one 600 mg capsule, twice a day — but where that comes from, I’ve no idea.
NAC should be stored refrigerated, since the cysteine can become oxidized.
N-acetylcysteine is a safe, over-the-counter supplement that replenishes glutathione. However, a test for glutathione is a highly specialized one, not performed by most clinical labs, and so you may not know if your glutathione level is low.
Most doctors, I think it safe to say, don’t know much about NAC, outside of its use for acetaminophen overdose. But you should consult your doctor anyway before taking it.
I can’t advise anyone on whether they should take NAC, but it appears to be useful in a number of chronic conditions.
You can buy n-acetylcysteine at Amazon, and most local health food stores, such as Whole Foods, carry it.