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Research · Supplements

N-acetylcysteine

A meta-analysis of sport trials found no change in performance, and side effects did not differ from placebo overall. In chronic bronchitis and COPD, two meta-analyses found 13% to 25% fewer exacerbations. Depression scores fell slightly as an add-on. With nitroglycerin, NAC was followed by intolerable headache and low blood pressure in angina trials.

Add to Bio HackChecked 2026-11-09
Status
FDA-approved prescription drug (acetylcysteine) for acetaminophen overdose and as a mucolytic. FDA's position is that NAC is excluded from the dietary supplement definition because it was approved as a new drug before it was marketed as a supplement. Since 2022, FDA has used enforcement discretion for NAC products labeled as dietary supplements that otherwise comply with the law [1].
Also called
NAC, N-acetyl-L-cysteine, acetylcysteine, Mucomyst, Acetadote
Taken for
antioxidant, glutathione, exercise performance, recovery, lung health, COPD, depression, bipolar disorder, PCOS, fertility, liver health

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help4

Reported risks2

What people take it for, and what was found

Shown to help4

Strong

Chronic bronchitis and COPD exacerbations

Shown to lower exacerbations in chronic bronchitis and COPD, about 13 to 25% fewer. The reviews disagree on which dose range showed it.

The numbers and sources
Effect
Across 13 studies (4,155 patients), NAC lowered exacerbations (RR 0.75, 95% CI 0.66 to 0.84). In spirometry-confirmed COPD, doses above 600 mg a day gave RR 0.75 (95% CI 0.68 to 0.82) [3]. A 2026 meta-analysis of 14 RCTs (2,856 COPD patients) found fewer exacerbations (RR 0.87, 95% CI 0.79 to 0.96). There, 600 mg a day or less gave RR 0.84 (95% CI 0.73 to 0.97) and higher doses RR 0.88 (95% CI 0.73 to 1.06). FEV1, FVC, St. George's Respiratory Questionnaire scores and glutathione did not improve [4]. A 2026 dose meta-analysis found FEV1, FVC and FEV1/FVC improved at 1,200 mg a day or more and not at lower doses [5].
Population
1,933 on NAC and 2,222 on placebo or control [3]; 1,295 on NAC and 1,314 controls in the exacerbation analysis of [4]; COPD trials from 2000 to 2024 [5].
Sources
[3], [4], [5]
Caveats
The effect was more apparent in patients without airway obstruction [3]. The two exacerbation reviews disagree on which dose range showed the effect [3][4]. The lung function reviews disagree, and [5] reported substantial heterogeneity for some outcomes.
Moderate

Depression symptoms

Shown to lower depression scores slightly when added to treatment, mainly in bipolar disorder.

The numbers and sources
Effect
Across 12 studies (904 patients), adjunctive NAC lowered depression scores compared with placebo (SMD -0.24, 95% CI -0.44 to -0.05, I² 45%) [6].
Population
Patients with bipolar disorder or major depressive disorder, 1,000 to 3,000 mg a day for 8 to 24 weeks [6].
Sources
[6]
Caveats
Wide confidence interval. The effect appeared mainly in bipolar disorder [6].
ModerateStudied in women

Polycystic ovary syndrome

Shown to raise progesterone and endometrial thickness in women with PCOS. These are hormone and ultrasound measures, not pregnancy rates.

The numbers and sources
Effect
Across 22 studies (2,515 women), NAC was associated with higher progesterone (SMD 0.95, 95% CI 0.13 to 1.77) and thicker endometrium (SMD 0.58, 95% CI 0.10 to 1.06) than placebo and other drugs. Estradiol, SHBG and FSH did not differ [7].
Population
Women with PCOS, compared with placebo, metformin or clomiphene [7].
Sources
[7]
Caveats
Hormone and ultrasound measures, not pregnancy or live birth rates. Comparators were mixed.
ModerateStudied in men

Male fertility and semen quality

Shown to improve sperm concentration, motility, morphology and semen volume in men with infertility, measured as semen quality rather than pregnancy.

The numbers and sources
Effect
Across 5 RCTs in men with infertility or impaired semen, NAC raised semen volume (MD 0.69 mL), sperm concentration (MD 4.43), total motility (MD 9.69) and normal morphology (MD 1.36) against control [8]. In 3 placebo-controlled trials in idiopathic male infertility, NAC improved sperm concentration, morphology, motility and ejaculation volume [9].
Population
Men with infertility or impaired semen parameters [8][9].
Sources
[8], [9]
Caveats
Few trials, likely overlapping between the reviews. Semen measures, not pregnancy or live birth. The abstract of [9] reports p-values only.

Not shown to help1

Moderate

Exercise performance

Not shown to change exercise performance in athletes and active adults, with a mean change of 0.29%.

The numbers and sources
Effect
Across 7 studies, mean performance changed by 0.29% (95% CI -0.67 to 1.25) [2].
Population
Athletes and active adults, typical dose 5.8 g a day, range 1.2 to 20 g [2].
Sources
[2]
Caveats
The authors note suboptimal reporting across trials [2].

Doses studied

Sport trials used a typical 5.8 g a day, range 1.2 to 20 g [2]. A dose-ranging handgrip study gave 9 to 140 mg per kg [10]. COPD trials compared 600 mg a day or less with more than 600 mg a day [3]. Depression trials used 1,000 to 3,000 mg a day [6].

Risks

Reported risks2

LimitedVery common

Interaction with nitroglycerin

Small trials found more headache and low blood pressure when NAC was given with nitroglycerin in hospital patients with unstable angina.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In 200 patients with unstable angina, oral NAC with transdermal nitroglycerin was followed by side effects in 35%, mainly intolerable headache, almost twice as often as nitroglycerin alone [11]. In 46 patients, intravenous NAC with intravenous nitroglycerin caused symptomatic hypotension in 7 versus 0 on nitroglycerin alone [12].
Population
Hospital patients with unstable angina [11][12].
Sources
[11], [12]
Caveats
Hospital doses, in [12] 5 g intravenously every 6 hours. The same combination also lowered cardiac event rates in both trials.
LimitedHow often is not known

Reactions to the drug form

Limited evidence: at antidote doses for acetaminophen poisoning, acetylcysteine has caused reactions from nausea to death, and intravenous dosing anaphylaxis-like reactions.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
As an antidote for acetaminophen poisoning, acetylcysteine has caused reactions from nausea to death, most deaths from incorrect dosing. Intravenous dosing causes anaphylaxis-like reactions with rash, itching, swelling and bronchospasm. Women and people with asthma or atopy were more susceptible [13].
Population
Patients treated for acetaminophen poisoning [13].
Sources
[13]
Caveats
Antidote doses are far higher than supplement doses. The review reports reaction frequency with oral dosing as at least as high as with intravenous dosing [13].

Checked, no increase found1

Moderate

Side effects in trials

Side effects were about as common on NAC as on placebo, with a suggestion of more at higher doses.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Across 17 studies, the odds of side effects on NAC versus placebo were 1.11 (95% CI 0.88 to 1.39), with a suggestion of more side effects at higher doses [2]. In COPD trials, adverse reactions were not dose-dependent [3], and adverse events did not rise against control in a 2026 meta-analysis [4]. At 140 mg per kg as a solution, gastrointestinal reaction intensity was higher than placebo, while 70 mg per kg did not cause significant adverse reactions [10].
Population
Exercise trial participants [2][10]; COPD patients [3].
Sources
[2], [3], [4], [10]
Caveats
Side effect reporting varied across trials [2].

Claims tested and not found

  1. That NAC improves sport performance. Mean performance changed by 0.29% (95% CI -0.67 to 1.25) [2].

Sources

  1. U.S. Food and Drug Administration. Policy Regarding N-acetyl-L-cysteine: Guidance for Industry; Availability. Federal Register 87(147). 2022. https://www.govinfo.gov/content/pkg/FR-2022-08-02/html/2022-16499.htm
  2. Rhodes K, Braakhuis A. Performance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis. Sports Medicine. 2017. https://doi.org/10.1007/s40279-017-0677-3
  3. Cazzola M, Calzetta L, Page C, et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. European Respiratory Review. 2015. https://doi.org/10.1183/16000617.00002215
  4. Cai X, Peng S, Mao S, et al. The efficacy of N-acetylcysteine in the management of chronic obstructive pulmonary disease: a systematic review and meta-analysis. PeerJ. 2026. https://doi.org/10.7717/peerj.21448
  5. Wang Y, Chen X, Huang J. Effects of different doses of N-acetylcysteine on lung function in patients with chronic obstructive pulmonary disease: a meta-analysis. BMC Pulmonary Medicine. 2026. https://doi.org/10.1186/s12890-026-04523-5
  6. Peng TR, Lin HH, Tseng TL, et al. Efficacy of N-acetylcysteine for patients with depression: An updated systematic review and meta-analysis. General Hospital Psychiatry. 2024. https://doi.org/10.1016/j.genhosppsych.2024.10.018
  7. Viña I, Viña JR, Carranza M, et al. Efficacy of N-Acetylcysteine in Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis. Nutrients. 2025. https://doi.org/10.3390/nu17020284
  8. Syarif S, Makkaraka MAG, Zainal ATF, et al. Unlocking the potential of antioxidant supplementation with n-acetylcysteine to improve seminal parameters and analysis of its safety: a systematic review and meta-analysis of randomized controlled trials. Archivio Italiano di Urologia e Andrologia. 2025. https://doi.org/10.4081/aiua.2025.13750
  9. Ma X, Yang Y, Liu S, et al. Meta-analysis of the efficacy and safety of L-carnitine and N-acetylcysteine monotherapy for male idiopathic infertility. Revista Internacional de Andrología. 2025. https://doi.org/10.22514/j.androl.2025.004
  10. Ferreira LF, Campbell KS, Reid MB. N-Acetylcysteine in Handgrip Exercise: Plasma Thiols and Adverse Reactions. International Journal of Sport Nutrition and Exercise Metabolism. 2011. https://doi.org/10.1123/ijsnem.21.2.146
  11. Ardissino D, Merlini PA, Savonitto S, et al. Effect of Transdermal Nitroglycerin or N-Acetylcysteine, or Both, in the Long-Term Treatment of Unstable Angina Pectoris. Journal of the American College of Cardiology. 1997. https://doi.org/10.1016/s0735-1097(97)00005-3
  12. Horowitz JD, Henry CA, Syrjanen ML, et al. Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris. Circulation. 1988. https://doi.org/10.1161/01.cir.77.4.787
  13. Sandilands E, Bateman D. Adverse reactions associated with acetylcysteine. Clinical Toxicology. 2009. https://doi.org/10.1080/15563650802665587

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