NAC (N-Acetylcysteine)
NAC (N-Acetyl Cysteine) is a supplemental form of the amino acid cysteine, best known for its powerful antioxidant and detoxification support. It helps replenish glutathione, the body's master antioxidant, and supports liver health, respiratory function, and immune defense. While cysteine is found in high-protein foods like chicken, turkey, eggs, dairy, and legumes, NAC itself is not found in food and is produced synthetically for use in supplements. It is commonly used for its role in managing oxidative stress, supporting detoxification, and promoting overall cellular health.
Benefits
Antioxidant Support
NAC boosts glutathione production, a critical antioxidant, helping neutralize free radicals and reduce oxidative stress. This supports overall cellular health and may protect against chronic diseases.
Liver Health and Detoxification
NAC is used medically to treat acetaminophen (paracetamol) overdose by restoring glutathione levels and preventing liver damage. It may also support liver function in cases of toxin exposure or fatty liver disease.
Respiratory Health
As a mucolytic, NAC breaks down mucus, improving symptoms in chronic respiratory conditions like chronic obstructive pulmonary disease (COPD), bronchitis, and cystic fibrosis. It may reduce exacerbations and improve breathing.
Mental Health Support
NAC shows promise in managing psychiatric conditions. It may reduce symptoms of depression, bipolar disorder, and obsessive-compulsive disorder (OCD) by modulating glutamate levels and reducing oxidative stress in the brain. It may also help with addiction (e.g., cocaine, cannabis) by curbing cravings.
Immune Function
NAC may enhance immune response by supporting glutathione levels and reducing inflammation, potentially aiding in infection resistance, though evidence is preliminary.
Fertility Benefits
In men, NAC may improve sperm quality by reducing oxidative stress. In women with polycystic ovary syndrome (PCOS), it may enhance ovulation and insulin sensitivity when combined with other treatments.
Mechanism of Action
Glutathione Precursor
NAC provides cysteine, a rate-limiting precursor for glutathione synthesis, boosting antioxidant defenses and protecting cells from oxidative damage.
Mucolytic Action
NAC breaks disulfide bonds in mucus proteins, reducing mucus viscosity and improving airway clearance in respiratory conditions like COPD or bronchitis.
Glutamate Modulation
In the brain, NAC regulates glutamate levels by modulating the cystine-glutamate antiporter, potentially reducing excitotoxicity and supporting mental health conditions like OCD or depression.
Detoxification
In acetaminophen overdose, NAC replenishes glutathione to neutralize the toxic metabolite NAPQI, preventing liver damage.
Anti-Inflammatory Effects
NAC inhibits pro-inflammatory pathways (e.g., NF-κB) and reduces cytokine production, mitigating inflammation in various conditions.
Clinical Trials
N-Acetyl Cysteine (NAC) Augmentation in the Treatment of Obsessive-Compulsive Disorder: A Phase III, 20-Week, Double-Blind, Randomized, Placebo-Controlled Trial
Study: This RCT (Sarris et al., 2022,) enrolled patients with obsessive-compulsive disorder (OCD) to assess NAC (up to 3,000 mg/day) as an adjunct to standard treatment over 20 weeks. Primary outcomes were Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores. Secondary outcomes included anxiety, depression, and quality of life
Findings: NAC showed no significant improvement in Y-BOCS scores compared to placebo (p>0.05). Subgroup analyses suggested modest benefits in treatment-resistant OCD, but results were not statistically significant. No serious adverse events were reported; mild gastrointestinal upset occurred in 10%. The study suggests limited efficacy for NAC in OCD, contrasting earlier smaller trials, highlighting the need for larger studies targeting specific OCD subtypes.
Link: Journal of Clinical Psychiatry
Safety and Efficacy of N-Acetylcysteine (NAC) as an Adjunct to Standard Treatment in Patients with Acute Ischemic Stroke: A Randomized Controlled Pilot Trial (NACTLYS)
Study: This RCT (Srivastava et al., 2024,, CTRI/2019/05/019305) at AIIMS, India, enrolled 50 patients with acute ischemic stroke (within 4.5 hours of onset), randomized to IV NAC (150 mg/kg) + recombinant tissue plasminogen activator (rtPA) or rtPA alone. Primary outcomes were intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes included National Institutes of Health Stroke Scale (NIHSS) at 24 hours, recanalization, and 3-month modified Rankin Scale (mRS).
Findings: NAC reduced infarct volume (140.27 vs. 226.07 mm³, p=0.0135) and NIHSS at 24 hours (p=0.03), indicating early neurological improvement. No significant differences were found in adverse events (p=0.99), intracranial hemorrhage (p=0.21), or 3-month mortality (p=0.99). The study suggests NAC is safe as an adjunct to rtPA and may improve early outcomes, but small sample size limits conclusions. Larger trials are needed.
Link: Scientific Reports
Prophylactic NAC Promoted Hematopoietic Reconstitution by Improving Endothelial Cells After Haploidentical HSCT: A Phase 3, Open-Label Randomized Trial
Study: This RCT (Wang et al., 2022,) involved 1006 patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), randomized to oral NAC (1,200 mg/day) or placebo. The primary outcome was hematopoietic reconstitution (neutrophil and platelet engraftment). Secondary outcomes included graft-versus-host disease (GVHD) and survival.
Findings: NAC significantly improved neutrophil engraftment (median 13 vs. 15 days, p<0.01) and platelet engraftment (median 19 vs. 22 days, p<0.05). GVHD incidence was unchanged (p>0.05). No serious adverse events were reported. The study supports NAC’s role in enhancing hematopoietic recovery post-HSCT, likely via endothelial cell protection, but long-term survival benefits are unclear.
Link: BMC Medicine
N-Acetylcysteine for Chronic Obstructive Pulmonary Disease and Chronic Bronchitis
Study: This RCT (Zhang et al., 2022,) evaluated NAC (1,200 mg/day) in 120 patients with stable chronic obstructive pulmonary disease (COPD) over 24 weeks. Outcomes included forced expiratory volume in 1 second (FEV1), exacerbation frequency, and quality of life (St. George’s Respiratory Questionnaire, SGRQ)
Findings: NAC maintained FEV1 (p<0.05) while placebo patients declined. Exacerbation frequency decreased (1.2 vs. 2.1 per year, p<0.01), and SGRQ scores improved (p<0.05). Mild gastrointestinal side effects occurred in 8%. The study aligns with the PANTHEON trial (1,200 mg/day,), which reduced exacerbations in moderate COPD, but contrasts with trials using 600 mg/day showing no benefit (e.g.,)
Link: BioMed Research International
Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
Study: This ongoing double-blind, placebo-controlled RCT (Shungu et al., 2020,, NCT04542161) at Cornell University is testing NAC (900 mg and 3,600 mg/day) in ME/CFS patients with low cortical glutathione (GSH). The primary outcome is change in GSH levels via proton magnetic resonance spectroscopy. Secondary outcomes include fatigue (CDC CFS Symptom Inventory) and cognitive function. A 2016 pilot study (n=small) found 1,800 mg/day NAC increased GSH and reduced symptoms
Findings: Preliminary 2016 data showed significant GSH increase and symptom reduction (p<0.05). The current trial (recruiting, completion expected 2025) aims to confirm these effects in a larger cohort. No adverse events were reported in the pilot. The study suggests NAC may address oxidative stress in ME/CFS, but results are pending.
Link: ClinicalTrials.gov
Potential Side Effects
Gastrointestinal Issues
Common side effects include nausea, vomiting, diarrhea, or abdominal pain, especially at higher doses (e.g., above 1,200–1,800 mg/day) or when taken on an empty stomach. Some users report flatulence or a bad taste in the mouth.
Skin Reactions
Mild skin rash or itching may occur, particularly in sensitive individuals. Rare cases of urticaria (hives) have been reported.
Allergic Reactions
Rare allergic reactions, such as swelling, rash, or difficulty breathing, may occur, especially with intravenous NAC (used medically) or in individuals sensitive to sulfur compounds. Severe allergic reactions (e.g., anaphylaxis) are very rare but possible, primarily with IV administration.
Low Blood Pressure
NAC may cause a slight drop in blood pressure, leading to dizziness or lightheadedness, particularly in individuals with low blood pressure or when combined with medications like nitroglycerin.
Headaches or Fatigue
Some users report mild headaches or fatigue, though these are uncommon and not well-documented.
Bronchospasm
In rare cases, particularly in individuals with asthma, NAC may cause bronchospasm or wheezing, especially with inhaled or high-dose forms.