N-Acetylcysteine (NAC)

A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Claims checked

• Protects the liver

  Not studied

  Liver & bile · healthy · No data

  No study of liver protection or liver values in healthy people found. NAC is established as an antidote in paracetamol poisoning, on a weak RCT and mainly observational basis ^[3]; this is a drug use in poisoned patients and not evidence for healthy people. The advertising claim “Raises glutathione and protects the liver” is split according to K4; the glutathione part appears as a marker in the next claim.

• Raises glutathione levels (marker only)

  Mixed results

  Liver & bile · healthy · Human, randomised

  Marker only. In a double-blind crossover study, glutathione rose only in people with a low baseline value, not at medium or high values ^[7]; a systematic review in men reports mostly an improved glutathione balance ^[8]. Area as for the split main claim.

• More endurance and athletic performance

  Mixed results

  Muscle & performance · healthy · Human, randomised

  Performance gains (VO2max +13.6%, time trial +15.4%, Wingate +11.4%) only in the group with low glutathione, not at medium or high baseline values ^[7]. A systematic review of 16 controlled studies in men reports mostly benefits, without meta-analysis ^[8].

• Helps against depression

  Small benefit

  Mood & stress · Patients: depression in bipolar disorder or major depression (adjunctive treatment) · Human, randomised

  Meta-analysis of twelve RCTs with 904 patients: SMD −0.24 (95% CI −0.44 to −0.05) in favor of NAC as an add-on, most clearly in bipolar disorder; because of the wide confidence interval, the authors consider larger studies necessary ^[9].

Mechanism of action

Glutathione is formed in the cell from glutamate, cysteine, and glycine; the supply of cysteine and the activity of the rate-limiting enzyme glutamate-cysteine ligase are decisive for the synthesis rate ^[1]. NAC is used as a cysteine donor for this pathway. After oral intake, however, only 6 to 10% reaches the circulation unchanged; the elimination half-life after infusion was about 2.3 hours, and the volume of distribution corresponded essentially to the extracellular space ^[2].

Intravenously, acetylcysteine serves as an antidote in paracetamol poisoning. A Cochrane review found only a few small RCTs with a high risk of bias: acetylcysteine appeared superior to placebo and had fewer adverse effects than dimercaprol or cysteamine; one small study pointed to lower mortality in fulminant liver failure. Current treatment rests mainly on observational studies ^[3]. With intravenous administration, non-allergic anaphylactoid reactions occur; simplified infusion regimens reduced them markedly in a meta-analysis, without more liver injury ^[4]. Errors in infusions with accidental overdose led in case reports to brain edema, hemolytic uremic syndrome, and deaths ^[5]. These drug findings concern poisoned patients and say nothing about liver protection in healthy people. Orally, acetylcysteine is approved as a mucolytic; the package leaflet of such a product names the liquefaction of mucus in cold-related bronchitis as an indication and describes, among other things, rare bronchospasms, very rare severe skin and hypersensitivity reactions, and interactions with glyceryl trinitrate and carbamazepine ^[6].

On the supplement claims: in a double-blind crossover study with 36 of 100 screened people, NAC over 30 days raised the glutathione level only in people with low glutathione, lowered oxidation markers, and increased performance (VO2max, time trial, Wingate); at medium and high baseline values, performance and redox status remained unchanged ^[7]. A systematic review of 16 controlled studies in men reports mostly benefits for performance, antioxidant capacity, and glutathione balance, but no clear effects on blood count, inflammatory response, and muscle parameters ^[8]. As adjunctive treatment in depression (mainly in bipolar disorder), a meta-analysis of twelve RCTs with 904 patients found a small effect (standardized mean difference −0.24; 95% CI −0.44 to −0.05) ^[9]. Studies with the combination GlyNAC (glycine and NAC) do not count for NAC alone; they are covered in the glynac profile.

Formulations and origin: NAC is available as effervescent tablets, granules, and capsules, as an extended-release tablet, and as an infusion solution (medicinal products). An extended-release tablet gave a flatter concentration curve and the lowest oral availability, a fast-dissolving tablet the highest (6 to 10% overall) ^[2]. Comparative data with a clinical endpoint were not found.

Targets

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

• ·Dopamineno data
• ·Noradrenalineno data
• ·Serotoninno data
• ·Acetylcholineno data
• ·Glutamate · AMPAno data
• ·Glutamate · NMDAno data
• ·GABAno data
• ·Histamineno data
• ·Orexinno data
• ·Adenosineno data
• ·Opioidsno data
• ·Melatoninno data
• ·Neurotrophinsno data
• ·Blood flowno data
• ·Nitric oxideno data
• ·Energy metabolismno data
• ·Insulin · glucoseno data
• ≈Inflammation · oxidativemodulated · Glutathione ↑ and oxidation markers ↓ only at low baseline glutathione; otherwise unchanged^[7][8]
• ·Stress axisno data
• ·Testosterone axisno data
• ·Endocannabinoidsno data
• ·Autophagy · senescenceno data
• ·Immune systemno data
• ·Lipid metabolismno data
• ·Coagulation · fibrinolysisno data
• ·Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

• Oral (swallowed) · Tablets, effervescent tablets, extended-release tablet

  6–10% (human)

  Rapid absorption with fast-dissolving forms; extended-release tablet with a flatter curve and lowest availability ^[2].

  Human, non-randomised

• Intravenous · Infusion (antidote)

  100%

  Standard route in paracetamol poisoning; anaphylactoid reactions possible, less frequent with simplified regimens ^[3][4].^[3][4]

  Human, non-randomised

Human studies

• Pharmacokinetics oral and intravenous

  open comparison of five dosage forms · healthy · n = 10 · single doses

  Measured: plasma levels, excretion

  Result: Oral availability 6–10%, t½ 2.27 h, volume of distribution 0.33 l/kg.^[2]

  Human, non-randomised

• Paracetamol poisoning

  Cochrane review of 11 RCTs · Patients: paracetamol overdose · n = 700 · acute

  Measured: liver injury, mortality, adverse effects

  Result: Acetylcysteine superior to placebo; quality of evidence low to very low.^[3]

  Human, randomised

• Performance by glutathione status

  double-blind crossover study, placebo-controlled · healthy (stratified by glutathione level) · n = 36 · 30 days

  Measured: VO2max, time trial, Wingate, redox markers

  Result: Better only at low glutathione; no effect at medium and high.^[7]

  Human, randomised

• Performance and biomarkers in men

  systematic review of 16 controlled studies · healthy (men) · varied

  Measured: performance, laboratory values, adverse effects

  Result: Mostly benefits for performance and glutathione; no severe adverse effects.^[8]

  Human, randomised

• Depression

  Meta-analysis of 12 RCTs · Patients: depression (bipolar, major depression) · n = 904 · 8–24 weeks

  Measured: depression score

  Result: SMD −0.24 (CI −0.44 to −0.05).^[9]

  Human, randomised

Risks and warnings

• Anaphylactoid reactions during infusion

  With intravenous administration as an antidote, non-allergic anaphylactoid, skin, and gastrointestinal reactions occur; simplified infusion regimens reduced them markedly (OR 0.24) ^[4].

  Human, non-randomised

• Severe consequences of infusion errors

  After accidental intravenous overdose, brain edema, seizures, hemolytic uremic syndrome, and deaths were described (review of 16 case reports) ^[5].

  Human, non-randomised

• Adverse effects with oral intake (product information)

  The package leaflet of an oral product lists occasional allergic reactions (rash, swelling, itching, hives, shortness of breath, rapid heartbeat, drop in blood pressure), headache, fever, inflammation of the oral mucosa, abdominal pain, nausea, vomiting, diarrhea, and tinnitus; rarely shortness of breath and bronchospasm, especially in asthma; very rarely bleeding, anaphylactic shock, and severe skin reactions (Stevens-Johnson and Lyell syndromes, usually with concurrent intake of other medicines). Platelet aggregation was impaired in several studies, with unclear clinical significance. As warnings it names bronchial asthma, previous or existing gastrointestinal ulcers, and histamine intolerance (with longer use) ^[6].

  Human, non-randomised

• Oral intake in sports studies

  No severe adverse effects were reported in the controlled sports studies ^[8].

  Human, randomised

Interactions

• Glyceryl trinitrate (nitroglycerin): According to the product information, possibly increased vasodilation with a drop in blood pressure that can be severe and manifest as headache ^[6].
• Carbamazepine: Decrease in the plasma carbamazepine level with possibly reduced efficacy ^[6].
• Cough suppressants: With concurrent use, a dangerous accumulation of secretions can occur because of the suppressed cough reflex ^[6].
• Antibiotics (tetracyclines, aminoglycosides, penicillins): Indications from experimental studies of reduced effect; cefixime and loracarbef are not affected according to the product information ^[6].
• Activated charcoal: Activated charcoal can reduce the effect of acetylcysteine ^[6].
• Laboratory tests: Acetylcysteine can affect the determination of salicylates and of ketone bodies in urine ^[6].

Fact check: common claims

• refuted

  “NAC replenishes glutathione stores in everyone”

  In a double-blind crossover study, glutathione rose only at a low baseline value, not at medium or high ^[7].

• not supported

  “NAC protects the liver because it helps in paracetamol poisoning”

  The antidote effect concerns poisoned patients ^[3]; for healthy people without poisoning there is no study of liver protection.

• partly supported

  “NAC is a natural antidepressant”

  As an add-on to a treatment, a small effect with a wide confidence interval, mainly in bipolar disorder ^[9]; not tested as sole treatment.

Pharmacokinetics

Absorption

Oral availability 6–10% ^[2].

Half-life

About 2.3 hours (late elimination phase after infusion) ^[2].

Metabolism

About 30% of total clearance via the kidney ^[2].

Legal status

Germany

Acetylcysteine is prescription-only, except for oral use in acute common cold illnesses in humans (AMVV Annex 1) ^[10]. The entry concerns medicinal products; whether NAC may be marketed as a dietary supplement was not checked (not verified). According to the package leaflet of an effervescent tablet product approved by the Belgian medicines agency, the same medicinal product is authorized in the European Economic Area, in Germany as an acetylcysteine product from Hexal; indication there: liquefaction of mucus and easier expectoration in cold-related bronchitis ^[6]. The German marketing authorization itself (AMIce) and the summary of product characteristics were not queried.

EU

No entry “acetylcysteine” or “cysteine” in the consolidated Union list of novel foods, as of August 10, 2026 ^[11]; in the EMA data export (October 24, 2026) no centrally authorized medicinal product with acetylcysteine.

USA

Not verified.

Related compounds

Open questions

• Do only people with low glutathione benefit, and how common is that in healthy people?
• How well tolerated is NAC as a long-term supplement, also with regard to training adaptations?
• Is the small effect in depression confirmed in large RCTs?