What do studies say about N-Acetyl-L-Cysteine (NAC)?

From the Guidelines

N-Acetyl-L-Cysteine (NAC) is a valuable treatment for acetaminophen overdose and has shown promise in reducing exacerbations of chronic obstructive pulmonary disease (COPD) and chronic bronchitis, with typical dosages ranging from 600-1200mg daily.

Key Points

• NAC serves as an antioxidant and precursor to glutathione, helping to reduce oxidative stress in the body 1.
• For acetaminophen overdose, NAC is the standard treatment, and its effectiveness is well-established, particularly when administered promptly 1.
• In patients with COPD and chronic bronchitis, oral NAC has been proposed as a mucolytic agent to aid in the elimination of secretions, with studies suggesting a reduction in the rate of exacerbations 1.
• NAC may also have benefits for psychiatric applications, such as obsessive-compulsive disorder, addiction, and certain mood disorders, at doses of 1200-2400mg daily.
• Common side effects include nausea, vomiting, and gastrointestinal discomfort, particularly at higher doses, and NAC may interact with certain medications, including some antibiotics and anticoagulants 1.

Recommendations

• For acetaminophen overdose, NAC should be administered as soon as possible, ideally within 8-10 hours of ingestion 1.
• For COPD and chronic bronchitis, NAC may be considered as an adjunctive treatment to reduce exacerbations, at a dosage of 600mg twice daily 1.
• Patients with existing health conditions or taking other medications should consult a healthcare provider before starting NAC, especially if they have asthma, as NAC may worsen symptoms in some cases.

From the FDA Drug Label

Long-term oral studies of acetylcysteine solution alone in rats (12 months of treatment followed by 6 months of observation) at doses up to 1,000 mg/kg/day (5. 2 times the human mucolytic dose) provided no evidence of oncogenic activity. Mutagenesis Published data1 indicate that acetylcysteine is not mutagenic in the Ames test, both with and without metabolic activation. Impairment of Fertility A reproductive toxicity test to assess potential impairment of fertility was performed with acetylcysteine (10%) combined with isoproterenol (0. 05%) and administered as an aerosol into a chamber of 12. 43 cubic meters. The only adverse effect observed was a slight non-dose-related reduction in fertility at dose levels of 500 or 1,000 mg/kg/day (2.6 or 5.2 times the human mucolytic dose) in the Segment I study.

Studies on N-Acetyl-L-Cysteine (NAC) indicate that:

• No evidence of oncogenic activity was found in long-term oral studies in rats at doses up to 5.2 times the human mucolytic dose 2.
• No mutagenic effects were observed in the Ames test, with or without metabolic activation 2.
• A slight non-dose-related reduction in fertility was noted at high doses (2.6 or 5.2 times the human mucolytic dose) in rat studies 2 and 2.
• No teratogenic effects were observed in rabbit and rat studies at doses up to 2.6 times the human dose 2 and 2.
• However, no adequate and well-controlled studies have been conducted in pregnant women, and the drug should be used during pregnancy only if clearly needed 2 and 2.

From the Research

Overview of N-Acetyl-L-Cysteine (NAC) Studies

• N-Acetyl-L-Cysteine (NAC) has been studied for its potential benefits in various medical conditions, including chronic bronchitis, cystic fibrosis, and chronic obstructive lung disease 3.
• The evidence suggests that NAC may be useful as an adjuvant in treating various medical conditions, especially chronic diseases, due to its potential mechanisms of action, such as reducing oxidative stress and inflammation 3.

NAC in Chronic Bronchitis

• Studies have investigated the effect of NAC on chronic bronchitis, with some showing a reduction in exacerbations and improvement in symptoms 4, 5.
• A meta-analysis found that NAC reduced the frequency of chronic bronchitis exacerbations and improved symptoms compared to placebo, without increasing the risk of adverse effects 4.
• However, not all studies have found significant benefits, with some showing no difference in lung function, mucociliary clearance, or sputum viscosity between NAC and placebo groups 6, 7.

Potential Benefits and Mechanisms of NAC

• NAC has been proposed as a potential treatment for various conditions, including polycystic ovary disease, male infertility, sleep apnea, and neurodegenerative diseases, due to its antioxidant and anti-inflammatory properties 3.
• The potential mechanisms of action of NAC include reducing oxidative stress, inflammation, and glutathione depletion, which may contribute to its therapeutic effects 3.

Adverse Effects and Safety

• The studies suggest that NAC is generally well-tolerated, with few adverse effects reported, and no significant difference in adverse effects between NAC and placebo groups 4, 5.
• However, gastrointestinal adverse effects, such as nausea and diarrhea, have been reported in some studies, and patients should be monitored for potential side effects 5.