N-acetyl cysteine (NAC) is a derivative of the amino acid L-cysteine. In the body, it is a source of sulfhydryl (-SH) groups, which allows it to act as a potent antioxidant. Also, N-acetyl cysteine increases glutathione levels in the body; glutathione deficiency is associated with a variety of pathological conditions (7868,64613,64681,64765,64770,64785).

WARNINGS

N-acetyl cysteine (NAC) is approved as a drug by the US Food and Drug Administration (FDA). Because it was approved as a drug before being marketed as a dietary supplement, the FDA considers NAC an unlawful ingredient in dietary supplements and has issued multiple warning letters for dietary supplement products containing NAC (104163). However, in August 2022, the FDA stated that it is considering a rule to allow the sale of NAC as a dietary supplement. Until a final ruling is made, the FDA intends to exercise enforcement discretion for sale and distribution of NAC as a dietary supplement, provided the products are not otherwise in violation of the Federal Food, Drug, and Cosmetic Act (108940).

Coronavirus disease 2019 (COVID-19): Despite claims to the contrary, there is no good evidence to support using N-acetyl cysteine for COVID-19. Recommend healthy lifestyle choices and proven prevention methods instead.

LIKELY SAFE ...when used orally, intravenously, intratracheally, or by inhalation and appropriately. N-acetyl cysteine is an FDA-approved prescription drug (832,1539,1705,1710,2245,2246,2252,2253,2254,2256)(2258,2259,2260,5808,6176,6611,7868,10270,10271,16840)(91243,91247,102027,102660,102666,99531).

CHILDREN: LIKELY SAFE ...when used orally and appropriately. N-acetyl cysteine has been safely used at doses of 900-2700 mg daily for 8-12 weeks (91235,91239,91241,102666). ...when used intravenously and appropriately. Intravenous N-acetyl cysteine 140 mg/kg/day plus oral N-acetyl cysteine 70 mg/kg four times daily for up to 10 months has been safely used (64547).

PREGNANCY: POSSIBLY SAFE ...when used orally, intratracheally, intravenously, or by inhalation. N-acetyl cysteine crosses the placenta, but has not been associated with adverse effects to the fetus (1711,64615,64493,97041). However, N-acetyl cysteine should only be used in pregnancy when clearly indicated, such as in cases of acetaminophen toxicity.

LACTATION: Insufficient reliable information available; avoid using.

•  Cardiovascular

  Intravenously, N-acetyl cysteine has been reported to significantly increase systolic and diastolic blood pressure after exposure to nitroglycerin when compared with placebo (2280). Tachycardia, chest pain, angina, and transient sinus bradycardia have been rarely reported after administration of intravenous N-acetyl cysteine (2280,7872,64658).
  
  Intratracheally, infants receiving 5% N-acetyl cysteine every four hours for chronic lung disease have developed bradycardia (64490).
  
  Orally, palpitations and chest tightness have been reported rarely in clinical research evaluating oral N-acetyl cysteine at doses up to 600 mg twice daily (64675,64717,64762).

•  Dermatologic

  Orally, N-acetyl cysteine may cause hives (64713,64739,64813), flushing (2260,64715), and edema (64714). Rash has also been reported (64510,64715,64717,102656). In one study, flushing was reported in 2% of patients receiving 600 mg of N-acetyl cysteine orally twice daily for six months (2260).
  
  Intravenously, N-acetyl cysteine may cause rash, and the occurrence seems to be more common than with oral use (2254,64492,64562,64658,64759,64794). Hives (2280,64794), facial edema (2280), flushing (64412), and pruritus (64658,64763) have also been reported. In a small case series of 10 healthy male patients receiving 150 mg/kg of intravenous N-acetyl cysteine for muscle fatigue, erythema was experienced 30 minutes after infusion. Other side effects reported by these patients include facial erythema, palmar erythema, and sweating (64763). In other clinical research, three patients developed an erythematous flare at the sites of previous venipunctures after receiving 5.5 gm/m2 of N-acetyl cysteine with doxorubicin therapy (64712). Pain, inflammation, and excoriation of the skin have been reported after a 20% N-acetyl cysteine solution leaked from the catheter in one patient (64726).

•  Gastrointestinal

  Orally, gastrointestinal complaints are the most common adverse effects reported with N-acetyl cysteine. These include heartburn (64608,64715,64717,64738,64739,102666), dyspepsia (1710,64715,64717,64724,64738), and epigastric pain (2260,10429,64715,64717). In one case report, esophagitis related to ulcerations occurred following intake of N-acetyl cysteine while in the supine position with inadequate water (102655). Other common side effects include loss of appetite (64715,64812), flatulence (2256,64510), diarrhea (64713,64715,97049), constipation (64715), dry mouth (64715,64724), nausea (7868,11430,64715,64724,64738,64812,97049), vomiting (64717,64724,64715,97049), gastric upset (64510,64545,97045,97049), acid reflux (108450), changes in bowel habits (108450), and intolerance to taste and odor (64510,64545). N-acetyl cysteine's unpleasant odor makes it difficult for some patients to take orally. Using a straw to drink N-acetyl cysteine solutions can improve tolerability. Additionally, placement of a nasogastric or duodenal tube and administration of metoclopramide or ondansetron can be helpful for patients unable to tolerate oral N-acetyl cysteine (17).
  
  Intravenously, N-acetyl cysteine may cause diarrhea (64712), dyspepsia, nausea, vomiting (64763), mild gastrointestinal upset (102657), and metallic taste (64763).
  
  When inhaled, N-acetyl cysteine may cause epigastric pain and throat irritation (64703,64707,64674).

•  Genitourinary

  Orally, dysuria was reported in 2% of patients receiving 600 mg of N-acetyl cysteine twice daily for 6 months in one clinical trial (2260).

•  Hematologic

  In general, hematologic adverse reactions are reported more frequently with intravenous N-acetyl cysteine compared with oral use. In surgical patients, decreased prothrombin time (1341,64511), prolonged coagulation time (64511), increased blood loss (64511,64644), and decreased platelet aggregation (64511) have been reported after administration of IV N-acetyl cysteine. In one clinical trial, six healthy patients were administered a loading dose of IV N-acetyl cysteine 10 mg/kg followed by 10 mg/kg per hour for 32 hours. All patients experienced a decrease in prothrombin time by 30% to 40%. The decrease prothrombin time (25.4 sec to 20.6 sec) reached a steady state after 16 hours (1341). In a clinical trial evaluating patients with acute myocardial infarction, hemorrhage occurred in three patients taking intravenous N-acetyl cysteine 10 mg/min, heparin (per study protocol), and aspirin (7872). Two pediatric patients receiving intravenous N-acetyl cysteine (loading dose: 140 mg/kg followed by 70 mg/kg) experienced episodes of coagulopathy; however, patients were being treated for acetaminophen overdose (64794).
  
  Hemoptysis was reported in six patients receiving 200 mg of N-acetyl cysteine orally twice daily for 6 months for treatment of chronic bronchitis (64739).

•  Immunologic

  Orally, anaphylaxis to N-acetyl cysteine has been rarely reported (64794). However, anaphylactic reactions to intravenous N-acetyl cysteine appear to be more common (1716,64412,64449,64628,64710,64711,64721,64786,64789).
  
  Anaphylactic reactions to N-acetyl cysteine have involved rash, angioedema, hypotension, and bronchospasm (64449,64711,64720). The mechanism of this reaction is unclear, but some data suggest it is not an immunologic hypersensitivity reaction but rather an acute toxic effect of N-acetyl cysteine (64786,64641,64720). Management guidelines for the treatment of anaphylactoid reactions to intravenous N-acetyl cysteine have been published. In most cases, treatment is not required or treatment with diphenhydramine or salbutamol is sufficient to continue or restart N-acetyl cysteine infusion. Antihistamines are useful in controlling and preventing recurrence of anaphylactoid symptoms (1716).

•  Musculoskeletal

  In one clinical trial, joint pain was reported in more than 15% of patients receiving oral N-acetyl cysteine (64608). In other research, one patient experienced pain in the legs while taking 600 mg of N-acetyl cysteine twice daily for the treatment of chronic bronchitis (64762).

•  Neurologic/CNS

  Orally, headache has been frequently reported with N-acetyl cysteine in clinical research (7873,11430,64510,64608,64672,64713,64715,64724,64762). Other less common adverse effects reported in patients taking oral N-acetyl cysteine at a total daily dose of 600-1200 mg include dizziness (64715,64717,64724,64762), tiredness (64675,64717), vivid dreams (102666), disorientation, and inability to concentrate (64673). One pediatric patient receiving oral N-acetyl cysteine (loading dose: 140 mg/kg followed by 70 mg/kg) experienced encephalopathy (64794).
  
  Intravenously, N-acetyl cysteine has been associated with rare neurologic adverse reactions , including headache (7872), lightheadedness (64763), and dystonic reactions (64794). In a previously healthy 2-year-old female, status epilepticus occurred during intravenous N-acetyl cysteine therapy for paracetamol ingestion (64781). Increased deterioration in bulbar function in patients with amyotrophic lateral sclerosis has also been reported with IV N-acetyl cysteine (2254).

•  Ocular/Otic

  While rare, blurred vision has been reported in research on oral N-acetyl cysteine (64715). Additionally, in a previously healthy 2-year-old female, status epilepticus followed by cortical blindness occurred during intravenous N-acetyl cysteine therapy for paracetamol ingestion. In this case, vision was almost completely recovered 18-months later (64781).

•  Psychiatric

  Intravenously, dysphoria was experienced 30 minutes after infusion of N-acetyl cysteine in 8 of 10 healthy males assessed in one clinical study (64763).

•  Pulmonary/Respiratory

  Respiratory adverse reactions to N-acetyl cysteine are most commonly reported with inhalable dosage forms. These include wheezing (64455,64707), bronchospasm (64455,64699), and cough (64455,64456,64703,64811). While less frequent, wheezing (64675), bronchospasm (64675), increased sputum production (7868), cough (7868,64510), decreased peak flow (64510), dyspnea (64714), and cold symptoms (64510) have been reported with oral N-acetyl cysteine in clinical research. A few cases of wheezing (64718,64719), cough (64763), and bronchospasm (64658) have also been reported with intravenous N-acetyl cysteine. Additionally, respiratory arrest has been reported in one case where a 16 year-old female was being treated for acetaminophen toxicity with intravenous N-acetyl cysteine (64450).
  
  Two premature infants receiving 5% N-acetyl cysteine via intratracheal instillation for the treatment of chronic lung disease had an increased frequency of cyanotic spells (64490).

•  Other

  Injection site reactions, including burning and phlebitis, have been reported in patients receiving IV N-acetyl cysteine (1341,64763). Fever associated with IV N-acetyl cysteine was reported in one patient during clinical research (64759).

• Adult

  Oral:

  N-acetyl cysteine has most often been used in doses of 600-1200 mg daily. Daily doses of 1200 mg or more are typically taken in divided doses. Higher doses of up to 1000 mg twice daily have been used for up to 6 months. See Effectiveness section for condition-specific information.
  
  

  Inhalation:

  N-acetyl cysteine solution for inhalation comes in 10% and 20% concentrations. Most often, 2-4 mL of the 10% solution or 1-2 mL of the 20% solution are used. The frequency of use depends on the condition being treated. See Effectiveness section for condition-specific information.
  
  

  Topical:

  N-acetyl cysteine has been used in various topical formulations, including as eye drops and a mouthwash. See Effectiveness section for condition-specific information.
  
  

  Parenteral (Intravenous/Intramuscular):

  Dosing of intravenous N-acetyl cysteine varies depending on the condition being treated. See Effectiveness section for condition-specific information.
  
  

• Children

  Oral:

  Research is limited; typical dosing is unavailable.
  
  

  Inhalation:

  N-acetyl cysteine solution for inhalation comes in 10% and 20% concentrations. Most often, 2-4 mL of the 10% solution or 1-2 mL of the 20% solution are used. The frequency of use depends on the condition being treated. Effectiveness section for condition-specific information.
  
  

  Parenteral (Intravenous/Intramuscular):

  Research is limited; typical dosing is unavailable.
  
  

• Standardization & Formulation

  In clinical research, N-acetyl cysteine has been administered orally, intravenously, topically, and as an inhalant. FDA-approved N-acetyl cysteine products are available as intravenous solutions, oral or inhalant solutions, or effervescent tablets for solution (93058,93059).

ACTIVATED CHARCOAL Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D N-acetyl cysteine might reduce the effects of activated charcoal, while activated charcoal might reduce the absorption of N-acetyl cysteine.  Details N-acetyl cysteine appears to reduce the capacity of activated charcoal to adsorb acetaminophen and salicylic acid (7869). Conversely, although clinical research suggests that although activated charcoal can reduce the absorption of N-acetyl cysteine by up to 40%, it does not seem to reduce its clinical effects (1755,22774,22775,64501,64647). Other clinical evidence suggests that activated charcoal does not affect the absorption of N-acetyl cysteine (22776,22777).

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, N-acetyl cysteine might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details Clinical research suggests that intravenous N-acetyl cysteine decreases prothrombin time, prolongs coagulation time, decreases platelet aggregation, and increases blood loss in surgical patients (64511,64644). Furthermore, in vitro research suggests that N-acetyl cysteine increases the anticoagulant activity of nitroglycerin (22780,64780).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, N-acetyl cysteine might increase the risk of hypotension when taken with antihypertensive drugs.  Details Animal research suggests that N-acetyl cysteine potentiates the hypotensive effects of the angiotensin-converting enzyme inhibitors (ACEIs) captopril and enalaprilat (22785). Theoretically, combining N-acetyl cysteine with other antihypertensive drugs might increase the risk of hypotension.

CHLOROQUINE (Aralen) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, N-acetyl cysteine might interfere with the antimalarial effects of chloroquine.  Details Animal research suggests that N-acetyl cysteine might reduce the antimalarial effects of chloroquine by increasing cellular levels of glutathione (22786).

NITROGLYCERIN Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B N-acetyl cysteine can increase the risk for hypotension and headaches when taken with intravenous or transdermal nitroglycerin.  Details Clinical research shows that concomitant administration of N-acetyl cysteine and intravenous or transdermal nitroglycerin can cause severe hypotension (2246) and intolerable headaches (2245,2280). Furthermore, in vitro research suggests that N-acetyl cysteine increases the anticoagulant activity of nitroglycerin (22780,64780).

 Details  Details

 ALLERGY

 ASTHMA

 BLEEDING DISORDERS

 PERIOPERATIVE

 CHLORIDE

 CREATININE

 KETONES

 LITHIUM

 SALICYLATE

Presentation

Accidental overdose has been reported in patients receiving intravenous N-acetyl cysteine. In most cases the dose given was 10 times the recommended dose. In other cases, the infusion was administered too rapidly or a subsequent dose was given too close in time to the previous infusion. Adverse events associated with these overdoses included hypotension and kidney failure. Death has also been reported after intravenous N-acetyl cysteine overdose; however, it is unclear whether the deaths were due to N-acetyl cysteine or to an acetaminophen overdose for which the N-acetyl cysteine was indicated (64711).

Treatment

There is insufficient reliable information available about the treatment of overdose with N-acetyl cysteine.

Absorption: The bioavailability of oral N-acetyl cysteine is low, ranging from 4% to 10% (64655,64678,64684). The low bioavailability may be attributed to deacetylation of N-acetyl cysteine in the intestinal mucosa and lumen (64655). In pharmacokinetic research, the area under the curve (AUC) in humans after a single oral 600 mg N-acetyl cysteine dose was 32.87 mcM/L, while the Tmax was about 0.7-1 hour for both 200 mg and 600 mg doses (64660,106887). Other research suggests that the Tmax is closer to 1.5 hours (64660). In patients receiving standard intravenous N-acetyl cysteine treatment for acetaminophen poisoning, the average plasma concentration of N-acetyl cysteine was 554 mg/L after the initial loading dose (150 mg/kg over 15 minutes). At steady-state, an N-acetyl cysteine level of 35 mg/L was maintained after 12 hours, and the AUC was 1748 mg/hr/L (64656). The AUC of N-acetyl cysteine is elevated in patients with cirrhosis (64788).

Distribution: Assessing the pharmacokinetics of N-acetyl cysteine is difficult because it binds to cysteine and other sulfhydryl molecules. Because these compounds are widely available in tissues, N-acetyl cysteine is rapidly removed from plasma (10268). N-acetyl cysteine is highly protein-bound (64729,64647). Some pharmacokinetic research shows that oral N-acetyl cysteine is approximately 50-64% protein-bound (64723,64647), with a volume of distribution of 0.33-0.59 L/kg (64647,64678,64684). At high concentrations, oral N-acetyl cysteine remains active in the human lung for approximately five hours (64723).

Metabolism: Animal research suggests that N-acetyl cysteine is rapidly metabolized to disulfides via deacetylation and oxidation (64725).

Excretion: The plasma clearance of N-acetyl cysteine was found to be 0.84 L/hr/kg after a 400 mg oral dose and 0.11 L/hr/kg after a 200 mg intravenous dose (64678). After intravenous treatment for acetaminophen poisoning, total clearance of N-acetyl cysteine was 3.18 mL/min/kg in one study (64656). N-acetyl cysteine has a renal clearance of approximately 30% (64684,64647). In other research, the fraction of an oral dose of 600 mg excreted in the urine in 36 hours is 3.7% (106887). The major excretory product of N-acetyl cysteine appears to be sulfate (64647). The half-life of intravenous N-acetyl cysteine has been reported to be less than 30 minutes in some pharmacokinetic research (64817). The terminal half-life of intravenous N-acetyl cysteine is around 5.6-5.7 hours while the terminal half-life of oral N-acetyl cysteine is around 6.25 hours both oral and intravenous N-acetyl cysteine range from 5.6-6.25 hours (64647,64656,64678). In other research, the half-life of oral N-acetyl cysteine after taking 600 mg orally twice daily for 3 days is 15.4 hours in Chinese individuals and 18.7 hours in Caucasians (106887). Patients with cirrhosis appear to have a slower plasma clearance and prolonged half-life (64788).

General: N-acetyl cysteine is the N-acetyl derivative of the amino acid L-cysteine (1705). N-acetyl cysteine is a precursor of glutathione, which is a potent antioxidant. Glutathione cannot cross the cell membrane, but N-acetyl cysteine easily crosses the cell membrane where it is converted to cysteine and, subsequently, glutathione. Reactive oxygen species (ROS) such as hydrogen peroxide and hydroxyl-free radicals reduce intracellular and extracellular concentrations of glutathione. N-acetyl cysteine is a very efficient way to replenish glutathione and reduce damage caused by ROS (1761,7874).

Antibacterial effects: N-acetyl cysteine cleaves the disulfide bonds of mucus glycoproteins, destabilizing biofilms. This could theoretically allow antibiotics to more easily reach bacteria that produce biofilms (106901).

Anticancer effects: Some in vitro and animal research suggests that N-acetyl cysteine has anticancer effects (64421,64425,64431,64432,64683,64769,64816). While the anticancer mechanism has not been determined, results from some in vitro and animal research suggest that N-acetyl cysteine inhibits the invasive activity and angiogenesis of tumor cells (1767). Additional animal models suggest that N-acetyl cysteine may promote anti-angiogenesis through angiostatin production, which promotes vascular collapse of the tumor (64470). Other animal research suggests that N-acetyl cysteine's antitumor activity is related to changes in TNF-alpha and TNF receptor processing (64787). Some in vitro research suggests that N-acetyl cysteine may inhibit the growth of hormone-independent prostate cancer cell lines via anti-NF-kappaB activity (64431). Other in vitro research suggests that N-acetyl cysteine's anticancer effects may be explained by enhanced adhesion of peripheral blood mononuclear cells to tumor cells (64747) or via inhibition of VEGF (vascular endothelial growth factor) production (64414).

Anticoagulant effects: Preliminary evidence indicates that N-acetyl cysteine can impair platelet aggregation (64511,64644). N-acetyl cysteine appears to increase synthesis of nitric oxide, a potent inhibitor of platelet function (10272).

Antidote effects (acetaminophen toxicity): N-acetyl cysteine is effective for acetaminophen hepatotoxicity because it restores glutathione levels in the liver and acts as an alternative substrate for conjugation of toxic acetaminophen metabolites (15). The mechanism of the protective action of N-acetyl cysteine against the toxicity of acetaminophen has been suggested to involve the inhibition of the O-deethylation of ethoxyresorufin (cytochrome P-448) (64691).

Anti-inflammatory effects: N-acetyl cysteine appears to reduce cellular production of pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) (1763). Some in vitro research shows that N-acetyl cysteine inhibits markers of inflammation, such as phospholipid metabolism, pro-inflammatory cytokine release, and protease activity (64442). Although the mechanism has not yet been elucidated, some in vitro research suggests that nitric oxide synthesis may explain some of the anti-inflammatory effects of N-acetyl cysteine (64469). Preliminary clinical research in adult females with fibrocystic breast disease shows that taking N-acetyl cysteine 600 mg orally once daily for 12 weeks modestly lowers markers of inflammation, such as C-reactive protein, when compared with placebo (109938).

In isolated neutrophils and monocytes, N-acetyl cysteine inhibited chemotaxis (64679), release of elastase, respiratory burst, and NF-kappaB activation (64499). However, when given orally, N-acetyl cysteine resulted in reduction of neutrophil activity and respiratory burst, but not chemotaxis (64677,64499). Control of redox-sensitive transcription factors by N-acetyl cysteine may play a role in its anti-inflammatory effects (64527). Also, intraoperative N-acetyl cysteine administration during liver transplantation increased plasma IL-4 and IL-10 (64620).

Antioxidant effects: The antioxidant effects of N-acetyl cysteine may explain its apparent ability to prevent adverse effects caused by toxic chemicals, drug reactions, and nonionic low-osmolality contrast agents (1762,6611). The antioxidant and free radical properties might also make N-acetyl cysteine useful in the treatment of pulmonary and cardiac disease (1705,1765). In chronic obstructive pulmonary disease (COPD) patients, N-acetyl cysteine administration counteracted the oxidative stress associated with oxygen administration; namely, it prevented the oxidization of erythrocyte GSH and protein (64495). After N-acetyl cysteine treatment of humans, there was a decrease in the production of superoxide anions by stimulated neutrophils (64793). In humans undergoing knee surgery, low-dose N-acetyl cysteine infusion resulted in significantly lower plasma, but not tissue, malondialdehyde (MDA; a marker of oxidative stress) levels upon reperfusion (64485). N-acetyl cysteine did not have an effect on MDA levels in COPD patients treated for 15 days (64609). Some in vitro research showed that N-acetyl cysteine prevented oxidative stress-induced suppression of IL-2 biosynthesis (64416). Other in vitro research showed that N-acetyl cysteine protected A431 epithelial cells against oxidative stress induced by quinine menadione (64751).

Antisepsis effects: Some animal research suggests that IV N-acetyl cysteine may improve some markers of sepsis. Dogs with E. coli-induced sepsis were treated with N-acetyl cysteine 150 mg/kg followed by a 20 mg/kg per hour infusion. Compared to a control, dogs receiving N-acetyl cysteine maintained a higher cardiac index, oxygen delivery, and left ventricular stroke work index and had lower systemic and pulmonary vascular resistance (64768). In additional animal research, dogs receiving the same dose of IV N-acetyl cysteine showed improved oxygen availability and decreased TNF release when compared with placebo after exposure to E. coli endotoxin (64757).

Antiviral effects: In patients with human immunodeficiency virus (HIV) disease, N-acetyl cysteine can increase levels of glutathione. Increased concentration of glutathione seems to reduce oxidative stress associated with HIV disease and to improve the number and activity of CD4 T-lymphocytes (1539). Despite this, most clinical research suggests that N-acetyl cysteine does not provide additional benefit to HIV patients (64482,64779,64798). Additionally, some in vitro research shows that N-acetyl cysteine might actually enhance growth of HIV in certain cell types. The mechanism of this activity is unclear (64783).

Cardiovascular effects: Some in vitro and animal research suggests that N-acetyl cysteine's antioxidant effects might inhibit LDL oxidation, slow the progression of atherosclerotic lesions, and increase expression of nitric oxide synthase in vascular smooth muscle cells (64409,64602,64800). However, preliminary clinical evidence shows that N-acetyl cysteine 1200-2400 mg daily does not improve oxidized LDL or serum lipids in healthy adults (64465). There is some interest in using N-acetyl cysteine to protect the heart after myocardial infarction. In clinical research, continuous infusion of N-acetyl cysteine in conjunction with nitroglycerin reduces myocardial infarct size and increases myocardial salvage in patients undergoing percutaneous coronary intervention (PCI) for a myocardial infarction. The extent of myocardial salvage was directly correlated with increased myeloperoxidase levels and reduced malondialdehyde levels. N-acetyl cysteine administration was also associated with a 42% reduction in median creatine kinase levels (97044).

Cystic fibrosis effects: While N-acetyl cysteine does not seem to benefit cystic fibrosis patients in clinical research, some evidence suggests that N-acetyl cysteine may have a role in this disease. In vitro research suggests that N-acetyl cysteine may induce electrolyte secretion from airway epithelial cells (64774). Additionally, in children, some evidence suggests that N-acetyl cysteine improves electrolyte transport across the epithelia via osmotic effects or alteration of certain factors which influence this transport (64447).

Dental effects: Some early clinical research shows that using a mouthwash solution containing N-acetyl cysteine reduces dental plaque or gingivitis (64687,102662). N-acetyl cysteine might reduce bacterial growth, including oral pathogenic bacteria, by breaking the disulfide bonds of bacterial proteins. N-acetyl cysteine may also inhibit bacterial adherence (102662).

Exercise performance enhancement: In human research, N-acetyl cysteine appears to increase exercise performance by reducing respiratory muscle fatigue (64618). The exercise benefits of N-acetyl cysteine are also purportedly due to its antioxidant effects (64595,64584,91248). N-acetyl cysteine also seems to improve potassium regulation, which plays a role in reducing fatigue (64529).

Heavy metal toxicity protective effects: Some animal research shows that N-acetyl cysteine acts as a chelating agent for certain heavy metals, including potassium dichromate, boric acid, and mercuric chloride (36849,64519). N-acetyl cysteine does not appear to be effective in the treatment of lead tetraacetate or cadmium intoxication (36849,64428). Some animal research also suggests that N-acetyl cysteine may protect embryos from the toxic effects of methyl mercuric chloride (64772). However, other animal research indicates that N-acetyl cysteine might actually increase the risk for teratogenic effects from mercury, chromium, and cadmium (64666). The mechanism for these differing results is unclear.

Immunomodulatory effects: In patients with systemic lupus erythematosus, N-acetyl cysteine appears to improve disease activity by blocking mTOR in T lymphocytes (91242). N-acetyl cysteine increased the number of CD4+ cells in patients with suboptimal glutathione levels (64758). In cells isolated from healthy adults and HIV patients, N-acetyl cysteine enhanced the antibody-dependent cellular cytotoxicity of neutrophils and mononuclear cells and partially reversed the antineoplastic drug 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced inhibition of neutrophils (64749). After N-acetyl cysteine treatment of humans, there was an improvement in neutrophil phagocytic capacity, although random or chemotactic migration was not affected (64793). Treatment with N-acetyl cysteine immunoenhanced CD4+ T cells isolated from 30 HIV+ and matching controls (64773). Mitogenesis was also enhanced in both groups approximately twofold. IL-2 production with activators anti-CD3, PMA, or anti-CD28 was enhanced two- to threefold for both groups. Treatment with N-acetyl cysteine, however, suppressed IL-4 production by activators anti-CD3 and anti-CD28, also in both groups. An in vitro study was conducted to evaluate the effects of glutathione, glutathione ester, and N-acetyl cysteine on the induction of HIV expression in the chronically infected monocytic U1cell line (64537). N-acetyl cysteine suppressed reverse transcriptase activity >90%. Longer incubation periods produced greater suppression of reverse transcriptase. N-acetyl cysteine also inhibited the induction of HIV protein synthesis. Other in vitro research showed that N-acetyl cysteine inhibited TNF-alpha-stimulated HIV replication as well as cytokine-enhanced HIV long-terminal repeat-directed expression of beta-galactosidase (64649). In vitro, N-acetyl cysteine suppressed human immunodeficiency virus in persistently infected cells (64446).

Nephroprotective effects: Some animal research suggests that N-acetyl cysteine improves outcomes after renal failure due to cadmium exposure, inferior vena cava occlusion, or ischemic kidney injury (64782,64796,64804).

Neurological effects: The glutamatergic and antioxidant properties of N-acetyl cysteine are purported to improve neuropsychiatric conditions such as autism (91239,91241), bipolar disorder (91234,91237,91243), and trichotillomania (16840,91235). There is also interest in using N-acetyl cysteine for improving compulsive behaviors, which is associated with hyperactivity in the cortical-striatum-thalamus-cortical circuits, possibly due to abnormal glutamate levels (97045). N-acetyl cysteine appears to increase the uptake of cysteine. Uptake of cysteine activates a reverse transport of glutamate into the extracellular space. Restoring glutamate to the extracellular space inhibits further release of glutamate which improves compulsive behaviors (16840).

Neuroprotective effects: N-acetyl cysteine may offer neuronal protection by preserving mitochondria and protecting motor neurons (64625). It is hypothesized that neuroprotection may also be facilitated via the scavenging of free radicals and reduction of oxidative stress beyond the blood brain barrier. There is some interest in using N-acetyl cysteine for fetal neuroprotection after diagnosis of intra-amniotic infection, or chorioamnionitis. Early research shows that administering N-acetyl cysteine 100 mg/kg intravenously every 6 hours until delivery decreases levels of vascular endothelial growth factor (VEGF), increases levels of interleukin-1 (IL-1), and reduces maternal cytokines, with no apparent negative effects on cardiovascular function or cerebral or systemic perfusion in the fetus or infant (97041).

Pulmonary effects: Some clinical, animal, and in vitro research suggests that, due to its antioxidant and anti-inflammatory effects, N-acetyl cysteine may help break down mucus and provide a protective effect against lung injury caused by cigarette smoke or ischemia (64423,64454,64510,64676,64682,64692,64696,64700,64707,64739)(64810,64811).

Thyroid effects: Preliminary clinical research in patients with non-thyroidal illness syndrome (NTIS) shows that taking NAC orally, 600 mcg daily for 12 weeks, reduces reverse triiodothyronine (rT3) levels when compared with placebo. There is no effect on free T3, free thyroxine (FT4), or thyroid stimulating hormone (TSH) levels (108942).