Evidence explainerNAC (N-acetylcysteine)
Is NAC Safe to Take Daily? What Long Trials and FDA's 2022 Policy Say
NAC has been taken daily for months to years in clinical trials, and FDA's first look found no safety concerns. Its legal status as a supplement is a separate, odder story.
Key takeaways
- In 13 studies (4,155 patients with chronic bronchitis or COPD), NAC was well tolerated and the risk of adverse reactions did not rise with dose [1].
- A Cochrane review of mucolytics, including NAC, given daily for 2 months to 3 years found no increase in adverse events versus placebo [2].
- In 6 add-on psychiatric trials (701 people), adverse reactions and dropouts were similar on NAC and control [3].
- FDA's initial review found no safety concerns with NAC in supplements, though its full review was ongoing as of August 2022 [4].
- FDA considers NAC excluded from the supplement definition because it was approved as a drug in 1963, but does not intend to object to most NAC supplements [4].
The evidence, graded
Pulled from our monograph evidence tables. Grades follow our evidence-grading policy.
- Grade BWorsenedRespiratory flare-up (exacerbation) ratePatients taking NAC had fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75); the effect was clearer in those without airway obstruction, and high doses were also effective in spirometry-confirmed COPD. Adverse reactions did not differ from placebo or rise with dose.
- Grade CMixedSymptom scores when added to standard psychiatric careAdjunctive NAC improved total psychopathology scores in schizophrenia (SMD -0.74, I² 84%) but had no significant effect in bipolar disorder and only a small effect on major depressive symptoms. Adverse reactions and dropouts were similar to control.
What daily-use trials report on safety
The longest NAC data come from lung trials. A 2015 meta-analysis of 13 studies (1,933 people on NAC, 2,222 on placebo or control) found NAC was well tolerated, and adverse reactions were not dose-dependent across low (600 mg/day or less) and high (over 600 mg/day) doses [1].
A 2019 Cochrane review of 38 trials of mucolytics, including NAC, given at least once daily for between 2 months and 3 years, found they were not associated with an increase in adverse events [2].
In a 2018 meta-analysis of 6 trials (701 people) where NAC was added to existing psychiatric care, adverse reactions and discontinuation rates were similar to control [3].
What these trials do not tell you
The long trials enrolled patients with chronic bronchitis or COPD, and the psychiatric trials added NAC to existing care, so they say little about healthy people [1][3]. In older adults, the GlyNAC trials were short: 2 weeks in 114 people and 16 weeks in 24 [5][6]. Both reported it was safe and well tolerated [5][6].
Why FDA says NAC is not a supplement
NAC (acetylcysteine) was approved as a new drug on September 14, 1963, and FDA found no evidence it was sold as a supplement or food before then [4]. Under the law, that excludes it from the dietary-supplement definition [4].
After petitions from two industry groups in 2021, FDA confirmed the exclusion on March 31, 2022 [4]. Its August 2022 guidance then said FDA intends to exercise enforcement discretion for NAC products labelled as supplements, noting they had been sold in the US for over 30 years [4].
That policy does not cover NAC products marketed for disease or products that are adulterated or misbranded [4]. FDA said it would likely propose a rule allowing NAC in supplements if its ongoing review finds no safety-related concerns [4].
Quick answers
Can NAC be taken every day?
Trials gave NAC daily for months to years, and pooled data found adverse reactions similar to placebo and not dose-dependent [1][2]. Talk to a pharmacist or clinician first if you take prescription medicines or have a chronic condition.
Why is NAC sometimes hard to find?
FDA concluded in 2022 that NAC is excluded from the supplement definition because it was approved as a drug in 1963 [4]. Its August 2022 guidance lets most NAC supplements stay on sale under enforcement discretion [4].
Does NAC have side effects?
The pooled abstracts report adverse reactions at rates similar to placebo or control, without listing specific effects [1][3]. We have not added a list that our sources do not support.
Does NAC raise glutathione?
Results are mixed; see NAC and glutathione [5].
Keep reading
Full monographs
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References
- [1]Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev, 2015.
- [2]Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease. Cochrane Database Syst Rev, 2019.
- [3]N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials. Acta Psychiatr Scand, 2018.
- [4]Guidance for Industry: Policy Regarding N-acetyl-L-cysteine. U.S. Food and Drug Administration, 2022.
- [5]A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Front Aging, 2022.
- [6]Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci, 2023.