N-Acetylcysteine (NAC)
Glutathione precursor with broad clinical uses.
Evidence tier
Moderate
Research weight
Citations
21 verified / 21
Classification
Gut & Immune
❝
What the evidence says. Several controlled trials; effects real but modest or context-dependent.
What is N-Acetylcysteine (NAC)?
N-Acetylcysteine (NAC) is a gut and immune supplement used for antioxidant (glutathione). NutriDex grades the human evidence as Moderate. NAC is a precursor to glutathione, the body's master antioxidant, and is an established medicine for acetaminophen overdose and as a mucolytic. As a supplement, controlled trials support adjunctive benefit in some psychiatric conditions (OCD, trichotillomania, addiction) and respiratory mucus clearance. Evidence is promising but uneven across the many conditions it's marketed for.
Purported Benefits
✓Antioxidant (glutathione)
✓Mucus thinning
✓Mental-health adjunct
✓Liver support
Evidence by outcome
The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.
| Outcome | Evidence | Effect | Studies |
|---|---|---|---|
| Acetaminophen-overdose antidoteEstablished life-saving emergency antidote; earlier administration lowers hepatotoxicity, oral and IV routes comparable. | Strong | ↑ benefit · large | 2 |
| COPD exacerbation prevention (mucolytic)Pooled RCTs (4,155 pts) reduced exacerbations (RR 0.75); confirmed COPD with obstruction needs high dose >=1200 mg/day. | Moderate | ↑ benefit · moderate | 3 |
| Depression (adjunct)Meta-analysis of 12 RCTs (904 pts) found NAC eased depressive symptoms at 1000-2750 mg/day; effect modest. | Moderate | ↑ benefit · small | 1 |
| OCD / trichotillomania (adjunct)OCD meta-analysis shows only modest, time-limited SSRI augmentation; one positive trichotillomania RCT (n=50); small, mixed. | Preliminary | ↔ mixed · small | 3 |
| Substance-use craving (adjunct)Meta-analysis of 9 RCTs supports reduced craving but flags high heterogeneity and publication bias; interpret cautiously. | Preliminary | ↑ benefit · small | 1 |
| Contrast-induced nephropathyLarge PRESERVE RCT (4,993 pts) definitively negative for renal protection; umbrella review's lower-incidence signal not borne out clinically. | Moderate | — no effect · negligible | 2 |
| Schizophrenia symptoms (adjunct)Meta-analysis found adjunctive NAC superior to placebo (medium effect, larger in acute phase); single pooled analysis. | Preliminary | ↑ benefit · moderate | 1 |
Dosing & Compounds
Typical Dose
600–1,800 mg/day; psychiatric trials often use 2,400 mg/day.
Active Compounds
Safety & Cautions
Generally safe. GI upset, rare bronchospasm in asthmatics. Regulatory status varies by country. Educational only — always check with your doctor or pharmacist before combining N-Acetylcysteine (NAC) with any medicine.
N-Acetylcysteine (NAC) drug interactions
Known or theoretical interactions between N-Acetylcysteine (NAC) and common medications — educational, not exhaustive. Always check with your doctor or pharmacist before combining N-Acetylcysteine (NAC) with any medicine.
Caution
Chemotherapy / radiation
Antioxidant NAC may theoretically protect tumor cells and blunt oxidative chemo/radiation — consult oncologist.
NAC replenishes glutathione and scavenges ROS, potentially reducing oxidative cytotoxicity. Antioxidants & supplements in cancer treatment (review)
Key Studies ★ 21 studies
Meta-analysis
Kishi 2023 (meta-analysis)
✓ Source
Meta-analysis of RCTs found adjunctive NAC superior to placebo for reducing total symptoms in schizophrenia (medium effect, larger in acute phase SMD approx -1.22).
Meta-analysis
Peng 2024 (meta-analysis)
✓ PubMed
Updated systematic review/meta-analysis of 12 RCTs (904 patients) found NAC more effective than placebo at alleviating depressive symptoms, with optimal doses of 1000-2750 mg/day.
Meta-analysis
Winterlind 2024 (meta-analysis)
✓ PubMed
Meta-analysis of 9 RCTs (623 participants) supported NAC for reducing substance craving in substance use disorders, but with high heterogeneity and publication bias warranting cautious interpretation.
Meta-analysis
Hosseini 2024 (OCD meta-analysis)
✓ Full text
Systematic review and meta-analysis of 6 RCTs (195 adults) found NAC augmentation of SSRIs provided modest benefit in obsessive-compulsive disorder with good tolerability.
Meta-analysis
Izquierdo-Condoy 2024 (COVID-19 meta-analysis)
✓ Full text
Meta-analysis of 5 RCTs (651 patients) found no statistically significant mortality reduction with NAC in COVID-19 (15.6% vs 32.3%; RR 0.58).
Meta-analysis
Nutrients 2025 (PCOS meta-analysis)
✓ Full text
Systematic review and meta-analysis found NAC improved metabolic and reproductive parameters in women with polycystic ovary syndrome, supporting its insulin-sensitizing antioxidant role.
Meta-analysis
Arch Ital Urol Androl 2025 (male infertility meta-analysis)
✓ PubMed
Systematic review and meta-analysis of RCTs found NAC supplementation significantly improved seminal parameters in men with infertility/impaired semen, with a favorable safety profile.
umbrella review
Yan 2023 (CIN umbrella review)
✓ Full text
Umbrella review of 12 meta-analyses (161 RCTs, 38,053 participants) found NAC significantly reduced contrast-induced nephropathy incidence (OR 0.72, 95% CI 0.65-0.79) but had no effect on dialysis need or mortality; evidence rated moderate quality.
meta-analysis
Orban 2024 (non-paracetamol ALF meta-analysis)
✓ Full text
Meta-analysis of 4 RCTs found intravenous NAC did not improve overall survival (OR 0.70, 95% CI 0.34-1.44) or transplant-free survival (OR 0.90, 95% CI 0.25-3.28) in non-paracetamol acute liver failure.
systematic review/meta-analysis
Yang 2023 (NAFLD meta-analysis)
✓ Full text
Transcriptomic analysis plus meta-analysis of preclinical studies found NAC significantly improved systemic and hepatic lipid metabolism in non-alcoholic fatty liver disease, supporting future clinical trials.
Meta-analysis
PMID 40728675 (2025)
✓ PubMed
Updated RCT meta-analysis found NAC may reduce COVID-19 mortality, particularly at higher doses or via non-oral (e.g. intravenous) routes, while concluding RCT evidence overall remains inconsistent.
Systematic review
Eghdami et al. 2024 (Front Psychiatry systematic review/meta-analysis)
✓ PubMed
Six RCTs (195 adults with moderate-to-severe OCD) of NAC augmentation of SSRIs. Total Y-BOCS improved over a 5-8 week window (p=0.05), but no significant benefit for treatment <5 weeks or >12 weeks, and no significant effect on obsession or compulsion subscores; adverse events did not differ from placebo. Overall: modest, time-limited augmentation signal.
Meta-analysis
Cazzola et al. 2015 (Eur Respir Rev meta-analysis)
✓ PubMed
Pooled analysis of 13 RCTs (4,155 COPD/chronic bronchitis patients) found NAC significantly reduced exacerbations (RR 0.75, 95% CI 0.66-0.84; p<0.01). In spirometrically confirmed COPD with airway obstruction, benefit required high dose (>=1200 mg/day; RR 0.75, 95% CI 0.68-0.82); 600 mg/day sufficed only without obstruction. Well tolerated, adverse-event risk not dose-dependent.
Systematic review
Green et al. 2013 (West J Emerg Med systematic review/meta-analysis)
✓ PubMed
16 studies, 5,164 acetaminophen-poisoned patients. Hepatotoxicity (transaminase >1000 IU/L) occurred in 12.6% of oral-NAC vs 13.2% of IV-NAC treated patients (no meaningful route difference); treatment delay was associated with higher hepatotoxicity, supporting early administration regardless of route.
Cochrane review
Cochrane (COPD)
✓ PubMed
Reduced exacerbations as a mucolytic.
randomized controlled trial
MASLD RCT 2025
✓ PubMed
Double-blind RCT in 69 MASLD patients (600 mg three times daily for 8 weeks) found no improvement in hepatic steatosis or liver enzymes, but significant reductions in fasting glucose, fasting insulin, HOMA-IR, and CRP versus placebo.
RCT
Weisbord et al. 2018 / PRESERVE (NEJM RCT)
✓ PubMed
2x2 factorial trial, 4,993 high-risk patients undergoing angiography. Oral acetylcysteine showed NO benefit vs placebo for the composite of death, dialysis, or persistent >=50% creatinine rise at 90 days (4.6% vs 4.5%; OR 1.02, 95% CI 0.78-1.33; p=0.88), nor for contrast-associated AKI. Definitively negative for renal protection.
RCT
Grant et al. 2009 (Arch Gen Psychiatry RCT)
✓ PubMed
12-week double-blind trial in 50 adults with trichotillomania. NAC (1200-2400 mg/day) produced significantly greater reductions in hair-pulling than placebo (MGH Hairpulling Scale p<0.001; PITS p=0.001); 56% of NAC patients 'much/very much improved' vs 16% on placebo (p=0.003), with separation emerging by week 9. No adverse events; well tolerated.
Review
Ooi 2018 review
✓ Full text
Adjunctive benefit in several psychiatric disorders.
Review
Matera/Cazzola et al. 2016 (Expert Rev Respir Med review)
✓ PubMed
Mechanistic and clinical review: NAC is a cysteine precursor for glutathione synthesis with mucolytic and anti-inflammatory actions countering COPD oxidative stress. Concludes NAC prevents COPD exacerbations at high dose (>=1200 mg/day), while 600 mg/day suffices in chronic bronchitis without obstruction.
Study
Acetaminophen-OD protocols
✓ Full text
Standard, life-saving antidote in emergency medicine.