NAC (N-acetylcysteine)
Summary
NAC's strongest human data come from long-term trials in people with chronic lung conditions, where it lowered flare-up rates. Exercise trials found less soreness and lactate but no performance gain in trained cyclists. Results for NAC combined with glycine in older adults are mixed. FDA permits NAC supplements under enforcement discretion.
Key facts
- No head-to-head human data between NAC products in our sources; GlyNAC trials test the combination, so NAC's own effect cannot be separated[6][7]
- Respiratory flare-ups in chronic lung conditions ↓ (B); repeated-sprint cycling performance: no effect (D); muscle soreness and lactate after exercise ↓ (meta-analysis without pooled n); glutathione in older adults: mixed (C/D)[2][5][8][6][7]
- About 600–1,200 mg/day or more in lung trials; 20 mg/kg before exercise; GlyNAC 2.4–7.2 g/day[2][5][7]
- FDA considers NAC excluded from the dietary-supplement definition but, under August 2022 guidance, exercises enforcement discretion for products labelled as supplements[1]
- 5 graded human outcomes on this page
- October 10, 2026
How it works
EstablishedNAC provides cysteine for synthesis of glutathione, an intracellular tripeptide that neutralizes reactive oxygen species (established). As a mucolytic, it is thought to make sputum easier to cough up (established). Glycine and cysteine are both required to make glutathione, the rationale for GlyNAC (proposed).[8][3][7]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Immune | Grade B | Worsened | Meta-analysis · n = 4,155 · 2015 | 1 row |
| Stress | Grade C | Mixed | Meta-analysis · n = 701 · 2018 | 1 row |
| Healthy aging | Grade C | No effect | RCT · n = 114 · 2022 | 2 rows |
| Performance | Grade D | No effect | Crossover RCT · n = 11 · 2019 | 1 row |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Respiratory flare-up (exacerbation) rate | Worsened | Grade B | Meta-analysis · n = 4,155 · 2015 Patients with chronic bronchitis or COPD in 13 studies (1,933 on NAC, 2,222 on placebo or control) Form: NAC · Dose: Low (≤600 mg/day) and high (>600 mg/day) dose groups · Duration: Varied across studies Patients 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. | 26324807 (opens PubMed)Source [2] |
| Symptom scores when added to standard psychiatric care | Mixed | Grade C | Meta-analysis · n = 701 · 2018 Patients with schizophrenia (3 RCTs), bipolar disorder (2) or major depressive disorder (1) on existing treatment Form: NAC (adjunctive) · Dose: Varied across trials · Duration: Varied across trials Adjunctive 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. | 29457216 (opens PubMed)Source [4] |
| Glutathione status in healthy older adults (GlyNAC) | No effect | Grade C | RCT · n = 114 · 2022 Healthy older adults (mean age 65) Form: glycine plus NAC (1:1) vs control · Dose: 2.4, 4.8 or 7.2 g/day · Duration: 2 weeks GlyNAC was safe and well tolerated but did not raise the reduced-to-oxidized glutathione ratio or total glutathione overall. In a subgroup with high oxidative stress and low baseline glutathione, the 4.8 and 7.2 g doses increased glutathione. | 35821844 (opens PubMed)Source [7] |
| Glutathione, oxidative stress and physical function in older adults (GlyNAC) | Improved | Grade D | RCT · n = 24 · 2023 Older adults (12 GlyNAC, 12 alanine placebo) Form: glycine plus NAC (GlyNAC) vs isonitrogenous alanine · Dose: Not stated in the abstract · Duration: 16 weeks GlyNAC, but not placebo, improved glutathione deficiency, oxidative stress, mitochondrial function, inflammation, insulin resistance, physical function, waist circumference and systolic blood pressure, and was well tolerated. | 35975308 (opens PubMed)Source [6] |
| Repeated 4-minute maximal cycling performance | No effect | Grade D | Crossover RCT · n = 11 · 2019 Well-trained cyclists Form: oral NAC vs placebo · Dose: 20 mg/kg before exercise · Duration: Single day, two efforts 90 minutes apart Mean power did not differ between NAC and placebo in either effort, and plasma antioxidant capacity was unchanged. | 31030296 (opens PubMed)Source [5] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| NAC capsules or tablets | Varies[1] | No head-to-head human absorption data in our sources.[2] | Adverse reactions did not differ from placebo in pooled lung trials and were not dose-dependent.[2][4] | Chronic lung conditions; exercise; add-on psychiatric trials |
| GlyNAC (glycine plus NAC) | Varies[7] | Raised glutathione only in a subgroup with high oxidative stress in a 2-week trial.[7] | Safe and well tolerated over 2 and 16 weeks in older adults.[6][7] | Healthy aging and glutathione status |
Studied doses
Doses studied in human trials ranged from about 600 mg to 3.6 g of NAC a day, from single servings before exercise to mucolytic trials lasting 2 months to 3 years.[2][3][5][7]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Medicines
- Nitroglycerin (intravenous)RCTIn a double-blind trial of 46 patients with severe unstable angina, intravenous NAC 5 g every 6 hours added to intravenous nitroglycerin led to symptomatic hypotension in 7 of 24 patients versus 0 of 22 on nitroglycerin alone. Anyone on nitrate therapy should check with their prescriber before adding NAC.[9]
Who should be careful
- Regulatory status
- NAC was approved as a new drug in 1963, so FDA considers it excluded from the dietary-supplement definition. Its 2022 guidance says FDA intends not to act against NAC products labelled as supplements, but this does not cover products that make disease claims. FDA's initial review found no safety concerns.[1]
- Psychiatric or lung conditions
- Trials studied NAC alongside prescribed care; it is not a replacement for it.[2][4]
- Before you start
- Talk to your pharmacist or clinician before adding this supplement, especially if you take prescription medicines, are pregnant or breastfeeding, or have a chronic health condition.[1]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
Articles about NAC (N-acetylcysteine)
Plain-English answers to common questions, built on the evidence above.
Frequently asked questions
Why is NAC sometimes hard to find as a supplement?
NAC was approved as a drug in 1963, before it was sold as a supplement, so FDA concluded in 2022 that it is excluded from the supplement definition. FDA's August 2022 guidance says it will exercise enforcement discretion for NAC products labelled as supplements, except products that make disease claims.[1]
Does NAC help athletic performance?
In well-trained cyclists, 20 mg/kg before two 4-minute efforts did not change power output. A meta-analysis of 20 studies found lower soreness and lactate after exercise, but performance gains were not shown.[5][8]
Sources
- [1]Guidance for Industry: Policy Regarding N-acetyl-L-cysteine (archived copy). U.S. Food and Drug Administration, 2022. guideline
- [2]Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis.. Eur Respir Rev, 2015. meta-analysis
- [3]Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive pulmonary disease.. Cochrane Database Syst Rev, 2019. systematic-review
- [4]N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.. Acta Psychiatr Scand, 2018. meta-analysis
- [5]N-Acetyl cysteine does not improve repeated intense endurance cycling performance of well-trained cyclists.. Eur J Appl Physiol, 2019. crossover-RCT
- [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. RCT
- [7]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. RCT
- [8]The impact of N-acetylcysteine on lactate, biomarkers of oxidative stress, immune response, and muscle damage: A systematic review and meta-analysis.. J Cell Mol Med, 2024. meta-analysis
- [9]Combined use of nitroglycerin and N-acetylcysteine in the management of unstable angina pectoris.. Circulation, 1988. RCT
What changed
- First draft. Every evidence-row PMID checked with NCBI E-utilities (esummary + efetch abstract) and re-read in an independent adversarial pass.
- Added the nitroglycerin interaction row (PMID 3127076) and replaced the dead FDA guidance link with an archived copy.