For Patients & Caregivers
How It Works
N-acetylcysteine is an effective drug for acetaminophen overdose and to break up mucus. It has not been proven to be an effective treatment for cancer.
N-acetylcysteine (NAC) is a compound that is found naturally in the body. It is converted to a chemical called glutathione, which plays a role in the detoxification of foreign substances in the body. It is used as an antidote for acetaminophen overdose. NAC itself is an antioxidant that is thought to neutralize free radicals that cause damage to DNA. Animals fed with NAC have less cellular damage and fewer lung, colon, and bladder tumors, compared with those fed a normal diet. In addition, NAC interferes with tumor invasion, metastasis, and blood vessel growth in lab experiments. However, few of these effects have been shown to occur in humans. An animal study shows NAC can speed up the growth of lung cancer cells due to its antioxidant activity.
NAC can dissolve and loosen mucus in patients with respiratory disorders such as chronic bronchitis and chronic obstructive pulmonary disease (COPD), but study results are mixed. Animal studies also show that it might protect against tissue damage from drugs such as doxorubicin, ifosfamide, and cyclophosphamide. These effects are currently being studied in humans.
NAC regulates glutamate levels in the brain. It has been studied for several psychiatric disorders in humans with limited success.
- To treat lung conditions such as bronchitis and COPD Clinical trials evaluating NAC for chronic bronchitis due to its mucus-digesting effect are mixed.
- To treat cystic fibrosis A meta-analysis found a small, but not very significant effect of inhaled N-acetylcysteine on lung function in patients with cystic fibrosis. A long-term study suggests it may help maintain lung function, but NAC had no effect on markers of inflammation. It was also not helpful for idiopathic pulmonary fibrosis.
- To prevent and treat cancer Most clinical trials do not support the use of N-acetylcysteine for treating cancer. A few clinical trials suggest that this supplement can prevent certain pre-cancerous damage, but there is no proof that it can prevent cancer.
- To treat drug-induced liver toxicity N-acetylcysteine is an effective treatment for acetaminophen poisoning, which can be life-threatening. If hepatic toxicity is suspected, seek immediate medical attention for proper treatment. One study also observed that NAC has a protective effect against liver toxicity from antituberculosis drugs.
- To treat cirrhosis Although N-acetylcysteine is known to be a precursor for glutathione, an important detoxification enzyme in the liver, there is no proof from clinical trials that this supplement can treat cirrhosis.
- To treat HIV and AIDS A few clinical trials suggest that N-acetylcysteine can raise cysteine and glutathione levels in HIV+ patients, but whether this supplement improves survival or immunity to disease is not known.
- To treat Lou Gehrig’s Disease (amyotrophic lateral sclerosis) This use has only been tested in one clinical trial, in which it was found that NAC had no effect on progression of disease or survival in patients with Lou Gehrig’s disease.
- To treat psychiatric disorders Several small scale studies suggest NAC may help to control substance abuse and gambling addictions. It may also help reduce symptoms of trichotillomania (hair pulling).
Do Not Take If
- Stomach upset
- Irritation of the conjunctiva of the eyes
- Skin rash
- Less commonly reported side effects include low blood pressure, anaphylactic shock, asthma attacks, and headache.
Light sensitivity: Occurred among pulmonary fibrosis patients taking acetylcysteine in combination with pirfenidone. The reaction could not be explained by causes such as location, season, or other medications taken at the same time.
- It is controversial whether antioxidants like N-acetylcysteine can lessen or negate the effects of chemotherapy and radiation therapy. Because these therapies work by creating free radicals that kill cancer cells, high levels of antioxidants may neutralize these effects and protect cancer cells from these therapies. So what protects healthy cells may protect cancer cells as well. Patients who are interested in taking antioxidants during therapy should consult with their doctor.
For Healthcare Professionals
N-acetylcysteine (NAC) is an antioxidant that is used as a prescription drug and as a dietary supplement. As a drug, it is given parenterally or orally to treat acetaminophen overdose. The inhalant and oral solution forms have a mucolytic effect to relieve obstructions in bronchial diseases and in tracheotomy procedures. The oral capsule is marketed as a dietary supplement for its liver protective function and is popular among patients with AIDS and cancer.
Clinical studies show NAC can treat drug-induced hepatotoxicity (1) (2), prevent and treat conditions of oxidative stress and reduce GSH levels caused by diseases such as HIV/AIDS (3) and cancer (4), and alleviate toxicity from chemo- and radiotherapy (4).
Results for treatment of chronic lung disease with NAC are mixed. NAC reduces the number of acute exacerbations in patients with chronic bronchopulmonary disease (5) and significantly improves lung function and endurance in COPD patients after exercise (6), but benefits were not observed in other trials (7) (8), including a study of high-dose NAC (37). In cystic fibrosis patients, long-term oral NAC maintained lung function but had no effect on biomarkers of neutrophilic inflammation (38). NAC was not helpful for idiopathic pulmonary fibrosis and did not alter the tolerability profile of pirfenidone (39); nor was it helpful for Lou Gehrig’s disease (10).
NAC has glutamate modulating effects (11) and has been tested as a treatment for psychiatric disorders (12) including addictions (13) and substance abuse (11). It also reduced symptoms of trichotillomania (14) .
Studies in smokers (15) and patients with a history of adenomatous colonic polyps (16) show NAC inhibits cancer biomarker development, although it did not inhibit the formation of secondary head and neck or lung tumors (17). In addition, NAC accelerated lung cancer growth in an animal model (36).
Preliminary studies suggest oral NAC may help reduce chemotherapy-induced neuropathy (18), but a single oral dose of NAC did not protect moles from UV-induced oxidative stress (42). In leukemia patients undergoing allogeneic hematopoietic SCT preceded by high-dose chemotherapy, parenteral NAC reduced incidence and duration oral mucositis (43).
Gastrointestinal side effects from the consumption of NAC have been reported (19). Due to its antioxidant activity, it may interfere with the actions of some chemotherapy drugs.
Mechanism of Action
NAC is a precursor to glutathione (GSH). It is used as both an antidote for acetaminophen-induced hepatotoxicity and as a mucolytic agent for respiratory diseases. NAC reduces disulphide bonds to sulfhydryl bonds to reduce mucus formation (20). Its hepatoprotective action may occur by cytokine-mediated mechanisms as well as GSH replenishment (21). In animal studies, NAC exhibits chemopreventive effects against lung (22), hepatocellular (23), esophageal (24), and immune system (25) cancers.
An in vitro study shows NAC may improve the benefit of ifosfamide by decreasing the risk of nephrotoxicity without interfering with the agent’s antitumor effect (26). Another study finds that NAC alters doxorubicin-induced NF-κB activity via concentration-dependent anti- and pro-oxidant mechanisms (27). This biphasic effect is also time-dependent (28). In androgen-independent human prostate cancer PC-3 cells, NAC has an antiproliferative effect by upregulating Cyr61 protein expression (28).
NAC amide can increase bioavailability and reduce oxidative stress, but it does not decrease doxorubicin-induced cell death in H9c2 cardiomyocytes (29). In an animal study, NAC increased lung cancer cell proliferation due to its antioxidant activity by reducing reactive oxygen species (ROS), DNA damage and p53 expression (36).
Photosensitivity not attributable to location, season, or concomitant medication: Occurred among pulmonary fibrosis patients more frequently with acetylcysteine than placebo in combination with pirfenidone (39).