Amino Acid

N-Acetyl L-Cysteine

N-Acetyl-L-cysteine

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

1,200–2,400 mg/day

watchEffect Window

8–12 weeks for behavioral/mood endpoints. Longer trials for some psychiatric subtypes.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

NAC is a cysteine donor that increases glutathione synthesis and acts as a mucolytic. It is used for respiratory mucus reduction, oxidative stress modulation, and certain compulsive-behavior targets.

Strong clinical evidence supports NAC as a mucolytic and as the standard antidote for acetaminophen toxicity in medical care. Trials also show benefits for some psychiatric conditions, including trichotillomania and obsessive-compulsive spectrum symptoms. Minority studies report improved insulin sensitivity and liver fat biomarkers. Gastrointestinal side effects can limit adherence, and effects vary by condition and dose.

NAC supports cysteine-glutathione pathways and may modulate glutamatergic signaling. Clinical effects are context-dependent and better for selected psychiatric adjunct use than broad cognition claims.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Adult compulsive-behavior symptom reduction (e.g., trichotillomania scales)
  • MADRS improvement in adjunctive bipolar depression protocols

Secondary Outcomes

  • Pediatric trichotillomania: no significant difference vs placebo
  • Possible delayed schizophrenia negative-symptom and working-memory effects in pooled analyses

Safety

Contraindications and Interactions

Contraindications

  • Pregnancy/lactation without clinician oversight
  • Asthma/bronchospasm history
  • High bleeding-risk states
  • Severe fluid-overload/cardiac disease

Side effects

  • Nausea
  • Vomiting
  • Diarrhea
  • Sulfur-like body odor

Interactions

  • Nitroglycerin
  • Carbamazepine
  • Procedural anticoagulation and perioperative contexts

Avoid if

  • Unstable mood episodes
  • Active severe respiratory reactivity
  • Recent major surgery without clinical review
  • Pediatric use outside specialist protocol

Evidence

Study-level References

n-acetyl-l-cysteine-SRC-001Randomized, double-blind, placebo-controlled trial
Sourceopen_in_new

PMID 19581567; DOI 10.1001/archgenpsychiatry.2009.60

Population: 50 adults with trichotillomania; 12 weeks; oral NAC 1,200–2,400 mg/day

Key findings: Favors NAC (56% much/very much improved vs 16% placebo. MGH-HPS/PIHTS improved, p<0.001)

Notes: Moderate risk from single-center, self-report components, limited follow-up.

Paper content

Favors NAC (56% much/very much improved vs 16% placebo; MGH-HPS/PIHTS improved, p<0.001)

n-acetyl-l-cysteine-SRC-002Randomized, double-blind, placebo-controlled add-on trial
Sourceopen_in_new

PMID 23452680; DOI 10.1016/j.jaac.2012.12.020

Population: 39 youth (ages 8–17), pediatric trichotillomania, 12 weeks

Key findings: No significant benefit on primary or secondary outcomes. 25% responders on NAC vs 21% placebo

Notes: Low-to-moderate power for age-stratified behavioral outcomes. Informative null result, but confidence limited by sample size.

Paper content

No significant benefit on primary or secondary outcomes; 25% responders on NAC vs 21% placebo

n-acetyl-l-cysteine-SRC-003Multicenter randomized, double-blind, placebo-controlled trial
Sourceopen_in_new

PMID 18534556; DOI 10.1016/j.biopsych.2008.04.022

Population: 75 adults with bipolar disorder in maintenance phase, 24-week adjunctive protocol

Key findings: Favors NAC on MADRS (LS mean diff -8.05, 95% CI -13.16 to -2.95, p=.002)

Notes: Post-hoc interpretation should be cautious. Primary episode-timing endpoint was null.

Paper content

Favors NAC on MADRS (LS mean diff -8.05; 95% CI -13.16 to -2.95; p=.002)

n-acetyl-l-cysteine-SRC-004Systematic review and meta-analysis of RCTs
Sourceopen_in_new

PMID 31826654; DOI 10.1177/0004867419893439

Population: 7 RCTs, n=220 NAC / n=220 placebo

Key findings: Suggests possible improvement in PANSS negative and total scores, and working memory at ≥24 weeks

Notes: Heterogeneous trial quality and outcome timing. Not definitive for broad clinical claims.

Paper content

Suggests possible improvement in PANSS negative and total scores, and working memory at ≥24 weeks

n-acetyl-l-cysteine-pmid-32726657Systematic review and meta-analysis of 28 controlled clinical trials.
Sourceopen_in_new

Faghfouri AH, Zarezadeh M, Tavakoli-Rouzbehani OM, Radkhah N, Faghfuri E, Kord-Varkaneh H, Tan SC, Ostadrahimi A. The effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials. Eur J Pharmacol. 2020;884:173368. doi:10.1016/j.ejphar.2020.173368. PMID:32726657.

Population: Adults across various clinical and healthy populations included in 28 controlled trials.

Dose protocol: Various NAC doses across 28 controlled clinical trials

Key findings: NAC significantly reduced malondialdehyde (SMD -1.44, P<0.001), IL-8 (WMD -2.56 pg/mL, P<0.001), and homocysteine (WMD -1.45, P=0.027). CRP and TNF-alpha were not consistently significant.

Notes: Supports NAC as effective for oxidative stress reduction, with more limited broad anti-inflammatory effects.

Paper content

This systematic review and meta-analysis pooled 28 controlled clinical trials to evaluate the effects of NAC supplementation on inflammatory and oxidative stress biomarkers. NAC significantly reduced malondialdehyde (SMD -1.44, P<0.001), IL-8 (WMD -2.56 pg/mL, P<0.001), and homocysteine (WMD -1.45, P=0.027). CRP, TNF-alpha, and IL-6 did not reach significance in the primary analysis, though sensitivity analyses suggested possible effects on some of these markers. The findings support NAC as an effective agent for reducing oxidative stress, with more limited evidence for broad anti-inflammatory effects.

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