INDEX

N-Acetyl Cysteine

Background

N-acetyl cysteine antioxidant

  • N-acetyl cysteine (NAC) is made from the amino acid L-cysteine. It is a source of sulfhydryl (-SH) groups and, thus, may act as a strong antioxidant.

  • Because it has the ability to thin mucus, NAC has been used traditionally as a decongestant. It has also been used to reduce poisoning associated with compounds such as acetaminophen and heavy metals.

  • NAC has been used clinically for approximately 40 years and has shown benefit for treating bronchiolitis and chronic bronchitis. Recent study has investigated its role as an antioxidant with the potential to treat HIV infection, cancer, and heart conditions. There is a lack of evidence of benefit in using NAC to prevent kidney impairment or to treat hepatitis, cystic fibrosis, or erythropoietic protoporphyria (a disorder caused by a defect in making heme).

  • NAC is generally well tolerated. The most frequent side effects are diarrhea, nausea, and vomiting. NAC is also well known for its unpleasant taste.

Scientific Evidence

Uses

Grade*

Acetaminophen toxicity

Strong scientific evidence supports the use of N-acetyl cysteine (NAC) as an antidote to acetaminophen overdose.

A

Bronchiolitis (sulfur mustard-induced)

NAC is commonly used for lung infections and sputum (phlegm and mucus) clearance. In human study, NAC reduced symptoms in patients with sulfur mustard-induced bronchiolitis (swelling in the small air passages of the lungs). Additional study is needed before a conclusion can be made.

B

Chronic bronchitis

NAC has been used to treat chronic bronchitis since the 1960s. Evidence from some human studies suggests that NAC may benefit patients with chronic bronchitis. Other studies show a lack of benefit. Further study is required before firm conclusions can be made.

B

Acute respiratory distress syndrome (ARDS)

Limited human study has investigated the effect of NAC on acute respiratory distress syndrome (ARDS). NAC may improve ventilation support. Additional research is needed.

C

Acute respiratory infections

Preliminary studies suggest that NAC may benefit patients with acute respiratory infections. Because the patients studied were also taking other medications, additional studies testing the effect of NAC alone are needed.

C

Addiction (gambling)

In preliminary study, NAC appeared to decrease measures of pathological gambling. Further well-designed research is required before a conclusion can be made.

C

Adrenoleukodystrophy (a type of fat breakdown disorder)

Preliminary evidence of benefit of NAC for adrenoleukodystrophy has been found. Further well-designed research is required before a conclusion can be made.

C

Alzheimer’s disease

Limited human study investigating the effect of NAC on Alzheimer’s disease has shown improvement in one assessment of memory and a lack of effect on others. Additional well-designed trials are needed before a conclusion can be made.

C

Amyotrophic lateral sclerosis

Limited study showed a lack of benefit of NAC in patients with amyotrophic lateral sclerosis. Further study is needed.

C

Angina (chest pain from clogged heart arteries)

Results of studies on the effect of NAC on angina are mixed. Further well-designed clinical trials are needed before a conclusion may be made.

C

Asthma

Preliminary study suggests that NAC may improve lung function in asthma patients. Additional study is required.

C

Cancer

Although not well-studied in humans, NAC has been shown to have a possible anti-cancer effect. However, preliminary human study reported a lack of benefit of NAC in increasing survival time of cancer patients. Additional research is needed before firm conclusions can be made.

C

Chemotherapy adverse effects

Limited study suggests that NAC may decrease side effects of chemotherapy. However, results from different studies conflict. Further well-designed clinical trials are required.

C

Chronic lung conditions (infantile)

There is a lack of sufficient evidence to make a conclusion on the use of NAC to treat chronic lung disease in infants. Preliminary human study suggests a lack of benefit of NAC in this group. Further study is required in this area.

C

Chronic obstructive pulmonary disease (COPD)

There is a lack of sufficient evidence to make a conclusion regarding the use of NAC in the treatment of chronic obstructive lung disease. Well-designed clinical trials are needed.

C

Cocaine withdrawal

Limited study showed that NAC may decrease the desire to use cocaine in cocaine-dependent patients. Well-designed study is needed before firm conclusions may be made.

C

Depression

In preliminary study, patients with bipolar disorder had decreased symptoms of depression when NAC was used together with standard treatment. Further well-designed study is required before a conclusion can be made.

C

Diminished appetite (high-altitude anorexia)

Preliminary study suggests that NAC may be ineffective in treatment of high-altitude appetite reduction. Further study is required before a conclusion can be made.

C

Dry eye syndrome

Preliminary research suggests that eye drops containing NAC may help treat dry eye syndrome. Further research is required.

C

Exercise performance enhancement

Antioxidants may decrease exercise-associated muscle pain and fatigue and, thus, may increase exercise endurance. In limited study, NAC increased exercise endurance. Further well-designed research is required before a conclusion may be made.

C

Female infertility

Preliminary research showed that NAC lacked benefit as an adjunct to a fertility drug in women with unexplained infertility. Further research is required before a conclusion may be made.

C

Heart protection during coronary artery bypass grafting (CABG)

NAC has been investigated for its potential to protect against heart damage following coronary artery bypass grafting (CABG). The clinical effects of NAC were unclear. Further research is required before firm conclusions may be made.

C

Helicobacter pylori infection

Although not well-studied in humans, NAC treatment was found to reduce the degree of Helicobacter pylori infection. Limited human research suggests NAC may provide additional benefit to antibiotic-treated patients infected with Helicobacter pylori. Further well-designed clinical trials are required before a conclusion may be made.

C

HIV/AIDS

The results of limited study on the effect of NAC on HIV/AIDS are unclear. Additional research is needed.

C

Hyperhomocysteinemia (high blood levels of homocysteine)

High blood levels of homocysteine may increase the risk of heart disease. Preliminary human study showed that NAC decreased homocysteine levels in patients with high blood levels of homocysteine, in patients with kidney disease, and in healthy people. It is unclear if NAC decreases the risk of heart disease. Well-designed studies are required before conclusions may be made in this area.

C

Hyperlipidemia (Lp(a))

Results of different studies investigating the effect of NAC on reducing levels of certain blood lipids conflict. Further evidence is required before a conclusion may be made.

C

Influenza prevention

Limited human study suggests that regular NAC use may help prevent influenza. Additional research is needed.

C

Malaria

In limited human research, NAC failed to help patients with malaria. Further research is needed before a conclusion may be made.

C

Male infertility

In limited research, NAC improved sperm concentration in infertile males. Further research is required.

C

Miscarriage prevention

In women with a history of miscarriages, NAC plus folate decreased the rate of miscarriage compared with folate treatment alone. Additional study is needed.

C

Multiple organ failure

Results of preliminary study suggest NAC may not prevent multiple organ failure. Further well-designed studies are required before a conclusion may be made.

C

Myocardial ischemia (decreased blood flow to the heart)

Results of preliminary research suggest that NAC may help patients who have had a heart attack. Well-designed human studies are needed before conclusions can be made.

C

Nosebleed

In preliminary research, NAC reduced the frequency and severity of daytime nosebleed. Further research is needed.

C

Organ transplantation (liver)

Preliminary study showed a lack of benefit of NAC in liver transplantation. Further research is required before a conclusion may be made.

C

Osteoporosis/post-menopausal bone loss

Results of study of NAC for osteoporosis/post-menopausal bone loss are unclear. Further well-designed research is required before a conclusion may be made.

C

Pancreatitis (inflammation of the pancreas)

In limited study, NAC lacked benefit for pancreatitis prevention. Further information is required in this field.

C

Peripheral artery disease

There is limited human study on the use of NAC for peripheral artery disease. Further well-designed research is required before a conclusion may be made.

C

Plaque formation

In preliminary study, an oral rinse containing NAC reduced plaque formation. Further research is required.

C

Polycystic ovarian syndrome

Limited evidence suggests NAC may increase ovulation and pregnancy and improve insulin levels in women with polycystic ovarian syndrome (PCOS). Results are mixed, however, and further research is needed.

C

Postoperative recovery (coronary)

NAC has been investigated for its potential in aiding recovery from heart surgery. Further research in this field is warranted.

C

Pregnancy support

NAC has been studied for its possible benefit in reducing preterm labor in pregnant women with a previous history of preterm labor. Further research is needed in this field before a conclusion may be made.

C

Schizophrenia

In preliminary research, NAC has been investigated as a treatment for schizophrenia. Further well-designed research is required before a conclusion may be made.

C

Sepsis

There is limited human study on the use of NAC for sepsis treatment. Further evidence is needed.

C

Sj�gren’s syndrome

There is a lack of sufficient evidence to make a conclusion for or against the use of NAC in the treatment of Sj�gren’s syndrome. Well-designed clinical trials are required.

C

Trauma (acoustic)

Limited study showed a lack of effect of NAC on hearing in people exposed to loud noise. Further research is required in this field.

C

Ulcerative colitis (a type of inflammatory bowel disease)

NAC has been investigated as a treatment for ulcerative colitis. Further well-designed research is required.

C

Cystic fibrosis

There is fairly strong evidence suggesting that NAC is not useful in the treatment of cystic fibrosis. Well-designed studies are needed to make a firm conclusion.

D

Erythropoietic protoporphyria (disorder involving abnormal heme synthesis)

Available evidence suggests NAC is ineffective for erythropoietic protoporphyria. Further evidence is required before a firm conclusion may be made.

D

Hepatitis

There is fairly strong evidence that NAC does not increase a hepatitis patient’s response to interferon therapy. Additional research is needed.

D

Kidney dysfunction (impairment)

Until further information is available, there is a lack of sufficient evidence for or against the use of NAC for the prevention of kidney damage. More research is needed.

D

*Key to grades:

A: Strong scientific evidence for this use;

B: Good scientific evidence for this use;

C: Unclear scientific evidence for this use;

D: Fair scientific evidence against this use (it may not work);

F: Strong scientific evidence against this use (it likely does not work).

Tradition

  • Abdominal pain, adjunct in surgery, aging, alcoholic liver disease, allergy, anti-inflammatory, antioxidant, arthritis, ataxia, attention-deficit hyperactivity disorder (ADHD), autism, autoimmune diseases, blood disorders, bile duct disorders, brain damage, burns, chronic fatigue syndrome, circulation improvement, common cold, congestive heart failure, diabetes, diabetic retinopathy, dialysis, ear infections, emphysema, epilepsy (Unverricht-Lundborg disease), fatigue, fibromyalgia, gallstones, hay fever, headaches, hearing loss, heart disease, heavy metal/lead toxicity, hepatitis B, immune function, infant development / neonatal care (meconium obstruction, intestinal obstruction), intestinal blockage (meconium ileus), kidney or bladder stones, kidney toxicity, liver disease, liver protection, lung cancer, lung problems, memory, meningitis, mental illness, metabolic disorders (glutathione synthetase deficiency, lysosomal storage disorders), mucilage, muscle pain, muscle weakness, nasal congestion, neuropathy, obesity, Parkinson’s disease, pneumonia, poisoning, premature labor prevention, radiation skin protection, Raynaud’s disease, retinitis pigmentosa, scleroderma, sinusitis, skin problems, smoking cessation, sports injuries, stroke, toxin/alcohol elimination from the body, urinary tract health (mucolysis).

Dosing

Adults (18 years and older)

  • Note: Intravenous or inhaled N-acetyl cysteine (NAC) should be used only under the supervision of a health care provider. All patients should consult a healthcare provider before starting any treatment.

  • For acetaminophen toxicity, an initial dose of 140 milligrams per kilogram NAC has been taken by mouth, followed by 70 milligrams per kilogram every four hours for 72 hours or until serum levels of acetaminophen were undetectable. A loading dose of 140-150 milligrams per kilogram body weight of NAC, followed by 50-70 milligrams per kilogram over four hours, with or without 100 milligrams per kilogram over 8-16 hours (or until serum acetaminophen levels were undetectable), has been used parenterally.

  • For acute respiratory distress syndrome, 150 milligrams per kilogram body weight of NAC has been delivered intravenously over 20 minutes the first day, followed by 50 milligrams per kilogram daily for three days.

  • For acute respiratory infections, 200-230 milligrams of NAC has been taken by mouth two to three times daily for 6-15 days.

  • For addiction to gambling, 600 milligrams of NAC, increasing every two weeks to a dose of 1,800 milligrams, has been taken by mouth for up to 14 weeks.

  • For angina, 2 grams of NAC in 100 milliliters of saline has been delivered intravenously over 15 minutes, followed by 5 milligrams per kilogram body weight per hour over 30 hours, as has 5 grams of NAC in 200 milliliters of 5% dextrose infused over 15 minutes, every six hours over a period of 24 hours.

  • For asthma, 0.5% nebulized NAC has been inhaled.

  • For exercise performance enhancement,125 milligrams per kilogram body weight of NAC per hour has been infused intravenously for 15 minutes, followed by 25 milligrams per kilogram body weight per hour for 20 minutes prior to and throughout exercise.

  • For sulfur mustard-induced bronchiolitis (swelling in the small air passages of the lungs), 1,200-1,800 milligrams of NAC has been taken by mouth in two or three divided doses daily for four months.

  • For chemotherapy adverse events, 5.5 grams per square meter body mass of NAC has been taken by mouth one hour before doxorubicin therapy every four weeks until the doxorubicin dose reached 300-350 milligrams per square meter or 500-550 milligrams per square meter. NAC at a dose of 1,200 milligrams has been taken by mouth 1.5 hours prior to oxaliplatin for 12 treatment cycles, with fluorouracil and leucovorin.

  • For chronic bronchitis, 200-600 milligrams of NAC has been taken by mouth twice daily for up to six months, as well as 300 milligrams of NAC in controlled-release tablets twice daily for six months.

  • For chronic obstructive pulmonary disease, 600 milligrams of NAC has been taken by mouth daily for six months.

  • For cocaine withdrawal, 600 milligrams of NAC has been taken by mouth every 12 hours for a total of four doses.

  • For depression, 1 gram of NAC has been taken by mouth twice daily for 24 weeks.

  • For diminished appetite (high-altitude anorexia), 400 milligrams of NAC has been taken by mouth daily with breakfast.

  • For dry eye syndrome, 20% NAC ophthalmic solution every two hours has been applied to the affected eye.

  • For female infertility, 1,200 milligrams of NAC has been taken by mouth daily for five days starting at day two or three of the menstrual cycle. Patients were also using clomiphene citrate.

  • For heart protection during coronary artery bypass grafting (CABG), an induction cardioplegia solution containing 4 millimoles per liter of NAC, and a maintenance cardioplegia solution containing 2 millimoles per liter of NAC has been delivered through a catheter. Also studied was a dose of 300 milligrams of NAC added to intermittent antegrade blood cardioplegia. Fifty milligrams per kilogram body weight NAC has been added to cold blood cardioplegia. For one hour before the procedure a dose of 50 milligrams per kilogram body weight has been intravenously infused, followed by intravenous infusion for 48 hours after the operation at a dose of 50 milligrams per kilogram body weight daily.

  • For Helicobacter pylori infection, 10 milliliters (400 milligrams) of NAC has been taken by mouth three times daily for 10 days with clarithromycin and lansoprazole.

  • For hyperhomocysteinemia (high blood levels of homocysteine), 600 milligrams of NAC has been taken by mouth daily for eight weeks. Five grams of NAC (Hidonac®) in 500 milliliters of 5% glucose has been intravenously infused for four hours in patients with end-stage kidney disease.

  • For influenza prevention, 600 milligrams of NAC effervescent tablets have been taken by mouth twice daily for six months.

  • For male infertility, 600 milligrams of NAC has been taken by mouth daily for 26 weeks.

  • For miscarriage prevention, 600 milligrams of NAC plus folic acid has been taken by mouth daily up to week 20 of gestation or miscarriage.

  • For myocardial ischemia (decreased blood flow to the heart), 100 milligrams per kilogram body weight NAC with streptokinase has been used intravenously six times daily. A loading dose of 20 milligrams per minute of NAC for one hour, followed by 10 milligrams per minute for 23 hours with streptokinase and nitroglycerine, has been delivered parenterally. A dose of 150 milligrams per kilogram body weight of NAC in 250 milliliters of 5% dextrose over 30 minutes or 15 grams over 24 hours with streptokinase has also been used.

  • For nosebleed, 600 milligrams of NAC has been taken by mouth three times daily for 12 weeks.

  • For organ transplantation, a 20% NAC solution in 0.9% saline (150 milligrams per kilogram body weight) 15 minutes prior to cardiac arrest has been intravenously infused, followed by 75 milligrams per kilogram body weight of NAC via portal vein in perfusion solution during cold phase dissection (1 gram per liter for 3 liters of citrate solution).

  • For pancreatitis, 600 milligrams of NAC has been given by mouth at 12 and 24 hours prior to endoscopic retrograde cholangiopancreatography, followed by 600 milligrams given intravenously twice daily for two days following the procedure. Six hundred milligrams of NAC has been administered intravenously 12 and 24 hours prior to endoscopic retrograde cholangiopancreatography, followed by 600 milligrams twice daily for two days after the procedure.

  • For plaque formation, 4 milliters of a 10% aqueous solution has been used in the mouth.

  • For polycystic ovarian syndrome, 1.2 grams of NAC has been taken by mouth daily, starting on day three of the menstrual cycle, for five days with clomiphene citrate. Another dose taken by mouth was 1.8-3 grams of NAC daily for 5-6 weeks.

  • For recovery after heart surgery, 600 milligrams has been taken by mouth the day before surgery, followed by a bolus of 150 milligrams per kilogram body weight delivered intravenously before skin incision, followed by perfusion at 12.5 milligrams per kilogram per hour for 24 hours.

  • For pregnancy support, 600 milligrams of NAC plus 17-hydroxyprogesterone caproate has been taken by mouth daily until 36 weeks of pregnancy or active labor.

  • For schizophrenia, two 500-milligram capsules of NAC have been taken by mouth twice daily for 24 weeks.

  • For sepsis, 150 milligrams per kilogram body weight NAC has been infused over 15 minutes, followed by a continuous infusion of 50 milligrams per kilogram body weight over four hours.

  • For Sj�gren’s syndrome, 200 milligrams of NAC has been taken by mouth three times daily for four weeks.

  • For ulcerative colitis, 800 milligrams has been taken by mouth daily for four weeks, in addition to mesalamine.

Children (under 18 years old)

  • Note: Intravenous N-acetyl cysteine (NAC) should be used only under the supervision of a health care provider. All patients should consult a healthcare provider before starting any treatment.

  • For acetaminophen toxicity, a loading dose of 140 milligrams per kilogram body weight of NAC, followed by 70 milligrams per kilogram body weight every four hours for 72 hours or until serum levels of acetaminophen were undetectable, has been taken by mouth. A loading dose of 150 milligrams per kilogram body weight of NAC over 15 minutes, followed by 50 milligrams per kilogram body weight over four hours, and then 100 milligrams per kilogram body weight for 16 hours (total duration varies) has been used parenterally.

  • For acute respiratory infection, 300-600 milligrams (depending on age) has been taken by mouth for eight days. A dose of 100-300 milligrams (depending on age) has been taken by mouth for six days.

References

  1. Baker WL, Anglade MW, Baker EL, et al. Use of N-acetylcysteine to reduce post-cardiothoracic surgery complications: a meta-analysis. Eur J Cardiothorac Surg 2009;35(3):521-527. View Abstract
  2. Brok J, Buckley N, Gluud C. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev 2006;(2):CD003328. View Abstract
  3. Charunwatthana P, Abul Faiz M, Ruangveerayut R, et al. N-acetylcysteine as adjunctive treatment in severe malaria: a randomized, double-blinded placebo-controlled clinical trial. Crit Care Med 2009;37(2):516-522. View Abstract
  4. Ghanei M, Shohrati M, Jafari M, et al. N-acetylcysteine improves the clinical conditions of mustard gas-exposed patients with normal pulmonary function test. Basic Clin Pharmacol Toxicol 2008;103(5):428-432. View Abstract
  5. Grandjean EM, Berthet P, Ruffmann R, et al. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther 2000;22(2):209-221. View Abstract
  6. Guijarro LG, Mate J, Gisbert JP, et al. N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: randomized, placebo-controlled pilot study. World J Gastroenterol 2008;14(18):2851-2857. View Abstract
  7. Ho KM, Morgan DJ. Meta-analysis of N-acetylcysteine to prevent acute renal failure after major surgery. Am J Kidney Dis 2009;53(1):33-40. View Abstract
  8. Keays R, Harrison PM, Wendon JA, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991;303(6809):1026-1029. View Abstract
  9. Minder EI, Schneider-Yin X, Steurer J, et al. A systematic review of treatment options for dermal photosensitivity in erythropoietic protoporphyria. Cell Mol Biol (Noisy-le-grand) 2009;55(1):84-97. View Abstract
  10. Moradi M, Mojtahedzadeh M, Mandegari A, et al. The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine. Respir Med 2009;103(3):434-441. View Abstract
  11. Nash EF, Stephenson A, Ratjen F, et al. Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis. Cochrane Database Syst Rev 2009;(1):CD007168. View Abstract
  12. Nigwekar SU, Kandula P. N-acetylcysteine in cardiovascular-surgery-associated renal failure: a meta-analysis. Ann Thorac Surg 2009;87(1):139-147. View Abstract
  13. Shohrati M, Aslani J, Eshraghi M, et al. Therapeutics effect of N-acetyl cysteine on mustard gas exposed patients: evaluating clinical aspect in patients with impaired pulmonary function test. Respir Med 2008;102(3):443-448. View Abstract
  14. Stey C, Steurer J, Bachmann S, et al. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J 2000;16(2):253-262. View Abstract
  15. Sutherland ER, Crapo JD, Bowler, RP. N-acetylcysteine and exacerbations of chronic obstructive pulmonary disease. COPD 2006;3(4):195-202. View Abstract