tuneTypical Dose
1200-1800
Supplement
N-Acetylcysteine
N-acetyl-L-cysteine
Evidence TierBWADA NOT PROHIBITED
watchEffect Window
Weeks for psychiatric/craving outcomes. Months for respiratory exacerbation reduction
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
N-Acetylcysteine is an antioxidant or precursor that supports glutathione dependent redox balance. It is taken for oxidative stress, respiratory support, and detoxification pathways.
N-acetylcysteine and related strategies can increase glutathione and reduce oxidative stress biomarkers in several settings. Trials show benefits for mucus clearance in chronic bronchitis and mixed results for exercise recovery and insulin sensitivity. Minority evidence includes fertility and psychiatric symptoms. Nausea and rare hypersensitivity reactions can occur.
Cysteine donor that replenishes glutathione, acts as mucolytic, and modulates glutamatergic signaling
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Reduced exacerbation burden in chronic bronchitis/COPD adjunct use
- Modest adjunctive depressive-symptom improvement in psychiatric populations
Secondary Outcomes
- Potential craving reduction signal in substance use disorders
- Select hormonal/metabolic improvements in PCOS (non-uniform)
Safety
Contraindications and Interactions
Contraindications
- Known NAC hypersensitivity
- Caution with active severe GI intolerance/peptic symptoms
- Caution in severe reactive airway history (especially non-oral formulations)
Side effects
- Nausea or GI upset
- Diarrhea/reflux
- Headache/sulfur taste-odor
Interactions
- Nitroglycerin and other nitrates (hypotension/headache risk)
- Additive BP-lowering regimens (monitor dizziness)
- High-burden antioxidant stacks (higher GI intolerance likelihood)
Avoid if
- Pregnancy/lactation without clinician guidance
- Recurrent hypotension/syncope
- Unsupervised chronic nitrate therapy
Evidence
Study-level References
n-acetylcysteine-SRC-001Cochrane systematic review/meta-analysis (mucolytics incl. NAC).
Sourceopen_in_newPoole P et al. Cochrane Database Syst Rev. 2019;5:CD001287. PMID: 31107966. DOI: 10.1002/14651858.CD001287.pub6.
Population: 38 RCTs; 10,377 adults with chronic bronchitis/COPD.
Dose protocol: Oral mucolytics >=2 months, mixed compounds including NAC.
Key findings: More participants exacerbation-free (Peto OR 1.73). NNTB ~8 over ~9 months.
Notes: Moderate-certainty with heterogeneity. Newer studies show smaller effects.
Paper content
More participants exacerbation-free (Peto OR 1.73); NNTB ~8 over ~9 months.
n-acetylcysteine-SRC-002Systematic review/meta-analysis (NAC-focused for chronic bronchitis).
Sourceopen_in_newWei J et al. Adv Ther. 2019;36(12):3356-3367. PMID: 31598901. DOI: 10.1007/s12325-019-01111-4.
Population: 11 studies; 775 NAC vs 789 placebo.
Dose protocol: Oral NAC, often <1200mg/day, duration >=3 months in effective subgroup.
Key findings: Exacerbation RR 0.81. Symptom improvement RR 1.68. No significant AE increase.
Notes: Includes older and regionally variable trials.
Paper content
Exacerbation RR 0.81; symptom improvement RR 1.68; no significant AE increase.
n-acetylcysteine-SRC-003Distinct meta-analyses for COPD and CB/pre-COPD.
Sourceopen_in_newPapi A et al. Arch Bronconeumol. 2024;60(5):269-278. PMID: 38555190. DOI: 10.1016/j.arbres.2024.03.010.
Population: 20 studies (subset CB/pre-COPD focused).
Dose protocol: NAC vs placebo, sensitivity analyses for durations >5 months.
Key findings: Exacerbation incidence reduced (IRR 0.76 COPD, 0.81 CB/pre-COPD). Symptom/QoL odds improved in CB/pre-COPD.
Notes: Study-level heterogeneity and mixed protocol designs.
Paper content
Exacerbation incidence reduced (IRR 0.76 COPD; 0.81 CB/pre-COPD); symptom/QoL odds improved in CB/pre-COPD.
n-acetylcysteine-SRC-004Systematic review/meta-analysis of RCTs.
Sourceopen_in_newPeng TR et al. Gen Hosp Psychiatry. 2024;91:151-159. PMID: 39504621. DOI: 10.1016/j.genhosppsych.2024.10.018.
Population: 12 studies; 904 participants with depressive symptoms in psychiatric disorders.
Dose protocol: 1000-3000mg/day for 8-24 weeks.
Key findings: Depression score change improved vs placebo (SMD -0.24).
Notes: Mixed diagnoses and moderate heterogeneity.
Paper content
Depression score change improved vs placebo (SMD -0.24).
n-acetylcysteine-SRC-005Meta-analysis of RCTs.
Sourceopen_in_newCuocina M et al. Front Pharmacol. 2024;15:1462612. PMID: 39309000. DOI: 10.3389/fphar.2024.1462612.
Population: 11 RCTs across alcohol/cocaine/poly-drug/amphetamine/nicotine SUD.
Dose protocol: Adjunct NAC vs placebo, duration and dose varied by trial.
Key findings: Craving reduction signal (SMD -0.61) with weak-certainty interpretation.
Notes: High heterogeneity for primary endpoint.
Paper content
Craving reduction signal (SMD -0.61) with weak-certainty interpretation.
n-acetylcysteine-SRC-006Systematic review/meta-analysis.
Sourceopen_in_newShahveghar Asl Z et al. Br J Nutr. 2023;130(2):202-210. PMID: 36597797. DOI: 10.1017/S0007114522003270.
Population: 18 studies; 2185 women with PCOS.
Dose protocol: NAC supplementation vs controls, trial regimens varied.
Key findings: Reduced total testosterone and increased FSH. Many fertility/endocrine endpoints unchanged.
Notes: Significant heterogeneity in several hormone endpoints.
Paper content
Reduced total testosterone and increased FSH; many fertility/endocrine endpoints unchanged.
n-acetylcysteine-SRC-007Double-blind cardiovascular clinical trial.
Sourceopen_in_newHorowitz JD et al. Circulation. 1988;77(4):787-794. PMID: 3127076. DOI: 10.1161/01.cir.77.4.787.
Population: 46 severe unstable angina patients on IV nitroglycerin +/- IV NAC.
Dose protocol: IV NAC 5g q6h with NTG in trial arm.
Key findings: Symptomatic hypotension occurred more frequently in NTG+NAC arm.
Notes: Older inpatient setting. Protocol not equivalent to modern supplement use.
Paper content
Symptomatic hypotension occurred more frequently in NTG+NAC arm.
n-acetylcysteine-SRC-008Systematic review/meta-analysis (performance and side effects).
Sourceopen_in_newRhodes K, Braakhuis A. Sports Med. 2017;47(8):1619-1636. PMID: 28102488. DOI: 10.1007/s40279-017-0677-3.
Population: 7 studies for performance; 17 studies for side effects.
Dose protocol: Typical dose ~5.8g/day (range 1.2-20g/day), often short-term protocols.
Key findings: No reliable ergogenic effect (mean performance change ~0.29%). Side-effect risk estimate uncertain.
Notes: Small samples and inconsistent adverse-event reporting.
Paper content
No reliable ergogenic effect (mean performance change ~0.29%); side-effect risk estimate uncertain.
n-acetylcysteine-pmid-32799012Systematic review and meta-analysis of 24 randomized clinical trials.
Sourceopen_in_newAskari M, Faryabi R, Mozaffari H, Darooghegi Mofrad M. The effects of N-Acetylcysteine on serum level of inflammatory biomarkers in adults. Findings from a systematic review and meta-analysis of randomized clinical trials. Cytokine. 2020;135:155239. doi:10.1016/j.cyto.2020.155239. PMID:32799012.
Population: Adults across 24 RCTs receiving NAC supplementation at doses of 400 to 2000 mg daily for 1 to 80 weeks.
Dose protocol: Oral NAC 400 to 2000 mg daily for 1 to 80 weeks across 24 RCTs (1,057 participants)
Key findings: NAC reduced CRP by 0.61 mg/L (P=0.039) and IL-6 by 0.43 pg/mL (P=0.001). Other inflammatory biomarkers were not significantly affected.
Notes: Supports modest anti-inflammatory effects of oral NAC supplementation, consistent with the oxidative stress meta-analysis (pmid-32726657).
Paper content
This meta-analysis of 24 RCTs with 1,057 total participants evaluated the effects of oral NAC supplementation on serum inflammatory biomarkers. NAC significantly reduced CRP by 0.61 mg/L (P=0.039) and IL-6 by 0.43 pg/mL (P=0.001). Other inflammatory biomarkers did not show significant changes. Doses ranged from 400 to 2000 mg daily over trial durations of 1 to 80 weeks. The findings support a modest anti-inflammatory effect of NAC supplementation, particularly on CRP and IL-6, though additional trials are needed to confirm dose-response relationships.