Acetylcysteine supplement health benefit, antioxidant uses, dosage
Safety, risk, and side effects
September 5 2018 by
Ray Sahelian, M.D.

N Acetyl l cysteine is made from the amino acid cysteine joined to an acetyl group. This nutrient (sometimes abbreviated as N-A-C  or NAC) is a strong antioxidant. It donates the amino acid cysteine to help form the antioxidant glutathione, a powerful natural antioxidant normally found in the body.

Health Benefit, how it can help you
N-acetylcysteine is an excellent source of sulfhydryl groups and is converted in the body into metabolites capable of stimulating glutathione synthesis, promoting detoxification, and acting directly as a free radical scavenger. Administration has historically been as a mucolytic [mucus dissolving] agent in a variety of respiratory illnesses; however, it appears to also have beneficial effects in conditions characterized by decreased glutathione or oxidative stress, such as HIV infection, cancer, heart disease, and cigarette smoking.

N-acetylcysteine (NAC) is pharmaceutically available either intravenously, orally, or by inhalation for reducing inflammation, fibrosis, invasion, cartilage erosion, acetaminophen detoxification, and transplant prolongation. It can be of benefit in improving the function of the endothelium.

Dosage, what is the right dose?
There are no accepted guidelines on the appropriate daily dosage. Some people may need none, others may benefit from taking 500 mg a few days a week. If you are taking other antioxidants, we suggest you reduce your dosage of n acetylcysteine. Some people think that the more antioxidants they take the healthier they will be, but there is no proof of this.

Anti aging and longevity, does it help you live longer?
Human studies are not available to determine whether regular intake, and what daily or weekly dose, has an influence on lifespan.

Thiolic antioxidant supplementation of the diet reverses age-related behavioural dysfunction in prematurely ageing mice.
Pharmacol Biochemical Behav. 2005.
We have studied in a model of premature ageing in mice the effect of the ingestion of thioproline plus N-acetylcysteine by female and male mice on performance in two behavior tests. The antioxidant treatment (4 weeks in two different periods of life, i.e., adult and old age) protected all animals against early-age-associated behavioral impairment, but this improvement was more evident in the prematurely ageing mice in comparison to the control group or non-prematurely ageing mice. These effects could be due to the glutathione precursor role of acetylcysteine and thioproline that replenish the intracellular reduced glutathione levels despite advancing age.

Athletics and physical exertion, exercise
N acetyl cysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals.
J Appl Physiology 2004.
The production of reactive oxygen species in skeletal muscle is linked with muscle fatigue. This study investigated the effects of the antioxidant compound acetylcysteine on muscle cysteine, cystine and glutathione, and on time to fatigue during prolonged, submaximal exercise in endurance athletes. Eight males completed a double-blind, crossover study, receiving acetylcysteine or placebo before and during cycling. The nutrient was intravenously infused for 20 min prior to and throughout exercise. This natural antioxidant improved performance in well-trained individuals, with enhanced muscle cysteine and GSH availability a likely mechanism.

Chemotherapy benefit during cancer treatment
There is a condition called "chemo-brain," which effects a large number of cancer patients receiving chemotherapy patients. Patients with this condition suffer from memory loss and have difficulty with focus and concentration. Dr. Gregory W. Konat at West Virginia University School of Medicine in Morgantown first gave one group of rats to two drugs commonly used to treat cancer, Adriamycin and Cytoxan. These drugs led to memory problems. However, memory loss was prevented when the rats were given n-acetylcysteine injections three times per week during chemotherapy. Metabolic Brain Disease, 2008.

J Laryngol Otol. 2016. Prevention of gentamicin ototoxicity with N-acetylcysteine and vitamin A. Gentamicin-induced hearing loss in rats may be prevented by the concomitant use of vitamin A and N-acetylcysteine. Specifically, N-acetylcysteine appeared to have a more protective effect than vitamin A for a greater range of noise frequencies.

N acetyl cysteine prevents cisplatin induced ototoxicity in rats
Hearing Research 2004.
Animals were treated with acetylcysteine or saline 15 or 30 minutes before receiving cisplatin or 4 hours afterward. The treated rats showed no significant change in auditory brainstem response with cisplatin therapy. In contrast, the saline-treated animals displayed marked ototoxicity (damage to hearing).

Would it also benefit those who have had radiation to the brain?
   I don't know for sure, but it is worth trying. 

Cocaine craving and addiction
Dr. Peter W. Kalivas from the Medical University of South Carolina, Charleston evaluated the effects of N-Acetylcysteine on cue-induced cocaine craving of 15 people with cocaine dependence. Those who were taking the supplements had less cocaine craving and interest evoked by depictions of cocaine use on photographic slides. The neurotransmitter system involved may be glutamate transmission. Dr. Peter W. Kalivas is now starting a double-blind study is being conducted to evaluate the effect of NAC on relapse rates and also evaluating the effects on nicotine and marijuana craving.

Am J Addiction 2013. A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence. The present report assessed the efficacy of NAC in the treatment of cocaine dependence. Cocaine-dependent volunteers were randomized to receive daily doses of 1,200 mg of NAC, 2,400 mg of NAC, or placebo. Participants were followed for 8 weeks (up to three visits weekly). At each of these visits, urine samples were collected, along with self-reports of cocaine use. Urine samples were assessed for quantitative levels of benzoylecognine (ie, cocaine metabolite). Overall, the primary results for the clinical trial were negative. However, when considering only subjects who entered the trial having already achieved abstinence, results favored the 2,400 mg NAC group relative to placebo, with the 2,400 mg group having longer times to relapse and lower craving ratings. While the present trial failed to demonstrate that NAC reduces cocaine use in cocaine-dependent individuals actively using, there was some evidence it prevented return to cocaine use in individuals who had already achieved abstinence from cocaine. N-acetylcysteine may be useful as a relapse prevention agent in abstinent cocaine-dependent individuals.

Is cocaine desire reduced by N-acetylcysteine?
Am J Psychiatry. 2007. LaRowe SD, Myrick H, Hedden S, Mardikian P, Brady K, Kalivas PW, Malcolm R. Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC,
In this double-blind, placebo-controlled trial, 15 volunteers received acetylcysteine or placebo during a 3-day hospitalization. Participants were crossed over to receive the opposite condition on a second, identical 3-day stay occurring 4 days later. During each hospital stay, participants completed a cue-reactivity procedure that involved collecting psychophysical and subjective data in response to slides depicting cocaine and cocaine use. While taking N-acetylcysteine, participants reported less desire to use and less interest in response to cocaine slides and watched cocaine slides for less time.

An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study.
Prog Neuropsychopharmacol Biol Psychiatry. 2007. Mardikian PN, LaRowe SD, Hedden S. Center for Drug and Alcohol Programs, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Twenty three treatment-seeking cocaine-dependent patients participated in a 4-week medication trial and received N-acetylcysteine at doses of 1200 mg / day, 2400 mg/day or 3600 mg per day. The majority of subjects who completed the study either terminated use of cocaine completely or significantly reduced their use of cocaine during treatment.

Fertility and infertility
I am not convinced yet that treatment with acetylcysteine NAC will help the majority of men or women with infertility. There are many other causes for this condition than would reduce the chances for NAC to be effective alone.

Reproductive Sci. 2015. N-Acetyl-Cysteine and l-Carnitine Prevent Meiotic Oocyte Damage Induced by Follicular Fluid From Infertile Women With Mild Endometriosis.

Mol Reprod Dev. 2014. Alpha-lipoic acid and N-acetylcysteine protects intensive swimming exercise-mediated germ-cell depletion, pro-oxidant generation, and alteration of steroidogenesis in rat testis. Prolonged and strenuous exercise has been proposed as a possible source of male-factor infertility. Forced intensive swimming has also been identified as one source of a dysfunctional male reproduction system. The present study evaluated the possible protective role of α-lipoic acid and N-acetylcysteine (NAC) on intensive swimming-induced germ-cell depletion in adult male rats.

Kidney disease and peritoneal dialysis
In patients with chronic kidney disease, inflammation and oxidative stress are cardiovascular risk factors. A study looked at the effect of oral NAC on plasma levels of inflammatory and oxidative stress markers in peritoneal dialysis patients. The eight week, placebo-controlled study included 30 patients on regular peritoneal dialysis. Twelve patients were treated twice daily with 600 mg of NAC and the remaining ten patients received placebo. NAC significantly decreased IL-6 levels without adverse side effects. Treatment reduced the inflammatory response in peritoneal dialysis patients. Nascimento MM, Suliman ME. Effect of oral N-Acetylcysteine treatment on plasma inflammatory and oxidative stress markers in peritoneal dialysis patients. Perit Dial Int. 2010.

N Acetyl cysteine in nephrology; contrast nephropathy and beyond.
Curr Opin Nephrol Hypertension. 2004.
At least 19 randomized trials evaluating acetylcysteine for the prevention of radiocontrast-induced nephropathy, at least five meta-analyses, and several reviews on that topic have been published within the past few years. One study indicated that long-term antioxidative treatment with acetylcysteine significantly reduced cardiovascular events in patients with end-stage renal failure. Although there are controversies on dosing and timing, its use together with hydration should be considered to protect patients from radiographic contrast media-induced nephropathy.

Nephropathy prevention
Researchers randomly assigned 354 consecutive patients undergoing primary angioplasty to one of three groups: 116 patients were assigned to a standard dose of N-acetylcysteine (a 600-mg intravenous bolus before primary angioplasty and 600 mg orally twice daily for the 48 hours after angioplasty), 119 patients to a double dose (a 1200-mg intravenous bolus and 1200 mg orally twice daily for the 48 hours after intervention), and 119 patients to placebo. Intravenous and oral N-acetylcysteine may prevent contrast-medium�induced nephropathy with a dose-dependent effect in patients treated with primary angioplasty and may improve hospital outcome.

MDMA, Ecstasy neurotoxicity
A rodent study showed potential reduction in neural damage from MDMA use.

Sickle cell disease
Annals Hematology. 2012. N-acetylcysteine reduces oxidative stress in sickle cell patients.

Trichotillomania or hair pulling treatment
N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study.
Arch Gen Psychiatry. 2009. Grant JE, Odlaug BL. Department of Psychiatry, University of Minnesota School of Medicine, Minneapolis, MN, USA.
Trichotillomania is characterized by repetitive hair pulling that causes noticeable hair loss. N-acetylcysteine seems to restore the extracellular glutamate concentration in the nucleus accumbens. Fifty individuals with trichotillomania (45 women and 5 men) were tested. Half received 1200 to 2400 mg/d of the supplement, and the other half placebo for 12 weeks. The treated patients had significantly greater reductions in hair-pulling symptoms as measured using the Massachusetts General Hospital Hair Pulling Scale and the Psychiatric Institute Trichotillomania Scale.

Tylenol toxicity, overdose, acetaminophen excess
In addition to its antioxidant properties, acetylcysteine is currently used to counteract the effects of an overdose of acetaminophen (i.e., Tylenol). Regular use of the painkiller acetaminophen is associated with higher rates of liver and kidney toxicity, asthma, and chronic obstructive pulmonary disease and reduced lung function. Animal experiments have suggested that acetaminophen might lower antioxidant activity in the lungs, and causes harm to the liver and kidneys. With hundreds of people each year dying from acetaminophen overdose, thousands more with liver damage or other health problems, why is acetaminophen still available for sale without a prescription whereas regulators have tried to pull away certain nutritional supplements that are far less toxic? Those who need to take the painkiller for a health condition should consider regular use of acetylcysteine, a nutrient that protects the liver from this drug's toxicity. As a resident, I prescribed intravenous N-acetylcyteine to patients with liver damage due to acetaminophen (Tylenol) overdose. It protected the liver quite well.

A patient-tailored N-acetylcysteine protocol for acute acetaminophen intoxication.
Clin Ther. 2005.
Liver toxicity as a result of acetaminophen (APAP) intoxication has become an important problem, but early intervention with N-acetylcysteine is effective in preventing hepatic injury.

I would like to use acetylcysteine to protect my liver from the amount of acetaminophin I am required to take on a daily basis due to my injuries. How much would I need to take?
    We have not seen any studies regarding the long term use of acetaminophen and acetylcysteine, however a dose of 100 mg a day or 250 mg a few times a week would seem reasonable.

Acetylcysteine side effects, safety and risk
Other than large doses causing nausea, acetylcysteine does not have any significant side effects and appears to be a safe nutrient as long as the dosage is kept to less than 500 mg. I experienced nausea for a few minutes within an hour of taking three 600 mg pills on an empty stomach.

I was wondering if I could overdose on NAC. What is the safest maximum per-day dosage?
   Each person has a different threshold for N acetyl cysteine, but as with most supplements, more is not better, there could be a feedback loop, or tolerance, or displacement of other crucial nutrients, etc. I personally prefer not to exceed 250 mg a few times a week, but a different doctor may have a different opinion.

Review and Recommendations
Acetyl cysteine is sold in dosages ranging from 250 to 600 mg. It can help form the powerful antioxidant glutathione but the formation of glutathione synthesis is under feedback control. Administration with the resulting increase in glutathione levels may cause a feedback inhibition in glutathione synthesis. Thus, it may be best to take it every other day. Its use certainly should be considered as an additional supplement in protecting various cells from damage in the elderly and those with Parkinson�s disease. If you are planning to use acetylcysteine along with other antioxidants, limit your daily dosage to 100 to 500 mg and don�t take it all the time.

What exactly is the difference between cysteine and the N Acetyl form? Which one is better to take?
   The latter has an additional acetyl group which makes it more potent as an antioxidant.

Review article for benefits
Neurosci Biobehav Rev. 2015. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable.

I wanted to let you know that my teenage son participated in a clinical trial at Yale for OCD with very good results. They used an effervescent formula (PharmaNAC) of 900 mg a day for the first two weeks, 1800 mg a day the second two, then 2700 mg per day after that. I have also tried it to reduce cigarette cravings and had significantly reduced cravings, although it irritated my bladder too much to continue. I wanted to share our experiences with you.

I am a mild asthmatic, adult onset, female, age 54. I have been taking 500 mg of N Acetyl cysteine daily for about six months. It has helped me manage my symptoms and reduce inhaled corticosteroids ICS required by reducing the amount and thickness of both chest and sinus mucus/phlegm.

I have been taking NAC for a couple of years now with great results -- 1200mg a day in a drink that I make that includes other vitamins and herbals just before breakfast. I have some interesting autoimmune issues: autoimmune thyroiditis, Raynaud's and erythromalalgia. For about 20 years I had consistent, elevated liver enzymes although for the last 4 years or so they have been normal. I added NAC after reading one of Sherri Roger's books on detoxification and found that I noticed a clearer head, less pain and overall improved energy. However, I have been taking many other nutritional supplements and have made some dramatic changes in my diet over the years.

Q. I have been searching on internet both scholarly articles and patient forums on whether NAC and SAM-e would combine or not? But except very few physicians, patients none had such experience. Do you have some experience to shed light?
   A. Any combination of supplements depends on the dosage, medications taken and a host of variables including diet, activity level, etc.

Additional products sold online
Jarrow Formulas, N-Acetyl-L-Cysteine, 500 mg, 200 Capsules

Natural Factors, N-Acetyl-L Cysteine, 500 mg, 90 Veggie Caps

Buy N Acetyl Cysteine, 500 mg per pill, 90 Capsules

N Acetyl Cysteine is a precursor in the body to the critical antioxidant glutathione, which is produced within cells, particularly by the liver. It is significantly more cost effective than taking glutathione pills.
Supplement Facts
Serving Size: 1 Capsule
  Amount Per Serving %Daily Value
N-Acetyl-L-Cysteine (Pharmaceutical Grade) 500 mg **
** Daily Value not established.