NAC and Glutathione

We evaluated 175 human studies on NAC and Glutathione, including 136 randomised controlled trials and 27 meta-analyses or systematic reviews; the controlled studies include 12,919 participants in total. As of 13 October 2026.

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1. What Is NAC and Glutathione? Occurrence, Origin and Forms

N-acetylcysteine (NAC) is a sulphur-containing compound and a precursor of the amino acid cysteine. Glutathione is a tripeptide of glutamate, cysteine and glycine that the body's cells produce themselves. In medicine NAC is used, among other things, to loosen mucus and as an antidote after a paracetamol overdose, while glutathione is used mainly as a dietary supplement.

Glutathione occurs in almost every cell of the body, with high levels in the liver. NAC and glutathione are offered as capsules, powders, drinks and in nebulised or infused form.

NAC is produced synthetically, glutathione synthetically or by fermentation. Studies in humans mainly examine oral capsules and powders, liposomal formulations, nebulised solutions and intravenous administration.

Forms and Preparations Studied

• Oral N-acetylcysteine (capsules, tablets, effervescent powder)
• Nebulised or inhaled N-acetylcysteine
• Intravenous N-acetylcysteine
• Oral glutathione (capsules, powder)
• Liposomal glutathione
• Intravenous glutathione

Not covered on this page:

• Other mucolytics such as ambroxol, bromhexine or carbocisteine are separate substances.
• Free cysteine, glycine or glutamine alone are neither NAC nor glutathione.
• Cysteine derivatives such as N-acetylcysteine amide (NACA) are separate substances.
• Combination products in which NAC or glutathione is only one ingredient alongside other active substances do not belong to the single substance.

2. What Does NAC and Glutathione Do? Results by Area

How to read the table: counted are human studies whose results concern the area. “High” means at least one meta-analysis and two controlled studies showing improvement, or at least three controlled studies of which three quarters show improvement, with at least 300 participants in total. “Moderate” means at least two controlled studies showing improvement, as a majority, or one meta-analysis alongside controlled studies. “Low” means one controlled study showing improvement. Where an area has no controlled study, the strength of evidence is at most “low” (result “reviews only” or “observational data only”). Everything else is “unclear”. A study counts as showing improvement when at least half of its outcomes in this area improved. Reviews of combination products do not count as meta-analyses; results that only describe side effects or shares of users do not count as an effect. The same study is counted only once.

3. What the Studies Show in Detail

NAC and Glutathione, Oxidative Stress and Antioxidant Status: Human Studies

Under oxidative stress, in several randomized controlled trials, oral N-acetylcysteine increased glutathione in the blood more than in the control group 4986. Another study found more glutathione in the follicular fluid during in vitro fertilization 39. Several randomized controlled trials also found less malondialdehyde, a marker of lipid peroxidation 5758108, and a higher total antioxidant capacity than in the control group 5786135. N-acetylcysteine as an inhalation spray lowered C-reactive protein in COVID-19 36, and given intravenously it increased catalase and glutathione peroxidase in organophosphate poisoning 92. These are contrasted by randomized controlled trials in which glutathione 69108 or malondialdehyde 7072 did not differ from the control. Most measured variables are blood or cell levels and thus markers, not clinical endpoints; the studies are predominantly small and short, and the overall robustness is high, but not for every individual measured variable.

Further studies in this area: 63 67 69 70 72 78 81 83 86 87 90 92 94 101 108 112 113 115 117 118 119 120 123 129 134 135 139 153

NAC and Glutathione and Mental Health Conditions: Human Studies

In mental disorders, the picture is mixed: one meta-analysis found a small advantage over placebo for depressive symptoms 4, another found no difference for psychotic disorders 9. A randomized controlled trial found less depression and anxiety under methadone maintenance therapy than under placebo 86; in bipolar depression, N-acetylcysteine alone did not differ from placebo 42. In obsessive-compulsive disorder, a meta-analysis found an advantage in the total Y-BOCS score only at five to eight weeks of treatment 15. One meta-analysis on trichotillomania rated N-acetylcysteine as well supported 18, another found no difference in the main analysis for PTSD 10. Almost exclusively oral N-acetylcysteine as an add-on to standard treatment was investigated; studies on nebulized or intravenous administration and on glutathione are still pending in this area. A factorial feasibility study with N-acetylcysteine and sodium benzoate in early schizophrenia found no main effects for most clinical measured quantities 73. Glutathione alone or together with vitamin C and N-acetylcysteine did not change behavior in autistic children 127.

Further studies in this area: 47 53 64 68 73 86 90 93 99 104 105 107 108 118 122 123 127 131 136 144 150 151 156 158

NAC and Glutathione, Addiction and Substance Use: Human Studies

Randomized controlled trials found advantages over placebo for smoking cessation with higher abstinence and less craving 60 and for general alcohol craving in adolescents 124. Compared with fluoxetine, N-acetylcysteine lowered alcohol craving more strongly 54, and in a small crossover study it reduced cocaine-induced drug-seeking behavior 133. For abstinence, controlled trials found predominantly no difference from placebo 404152. Two meta-analyses reach different results: one found an advantage for craving but none for withdrawal symptoms 22, the other found no difference for alcohol craving 10. Almost exclusively oral N-acetylcysteine was investigated, mostly as an add-on to counseling or standard therapy; nebulized, inhaled or intravenous applications as well as glutathione were not tested in this area. The overall strength of evidence is high, since many randomized controlled trials are available, but the heterogeneity of the findings and the mostly short duration do not allow a clear clinical effect to be recognized.

Further studies in this area: 50 52 53 54 60 93 94 107 115 123 124 125 129 133 152 156

NAC and Glutathione, Respiratory Tract and Lungs: Human Studies

In tuberculosis, oral N-acetylcysteine improved lung function (FVC) more strongly than standard therapy alone, without faster culture conversion 49. In bronchiectasis, it improved FVC and quality of life in the social functioning domain compared with placebo 128. Given orally or nebulized, it improved treatment response and sputum conversion in newly diagnosed tuberculosis 58. In COVID-19, quality of life in the SGRQ total score improved faster under oral N-acetylcysteine than under placebo 75. A randomized controlled trial in outpatients with COVID-19 reported fewer hospital admissions under N-acetylcysteine than under standard care 37143. In an open-label randomized study, N-acetylcysteine as an inhalation spray lowered mortality in COVID-19 36. This contrasts with results showing no difference: in COPD, oral N-acetylcysteine changed neither the exacerbation rate nor FEV1 compared with placebo 27. In ARDS, there was no advantage in mortality, oxygenation or need for ventilation 11. In lung fibrosis, N-acetylcysteine in addition to pirfenidone brought no confirmed advantage over pirfenidone alone 12. A meta-analysis of several mucolytics together does not allow a statement about N-acetylcysteine alone 21. It remains open which dose and duration are optimal for the individual diseases and whether the improvements in lung function and quality of life persist in the long term.

Further studies in this area: 49 56 58 61 75 97 128

NAC and Glutathione and Liver: Human Studies

In liver diseases, a mixed picture emerges: several controlled studies found improved liver enzymes with oral N-acetylcysteine, including in tuberculosis patients on standard therapy and in cirrhosis 5885120. In liver transplantation with long cold ischemia time, intravenous N-acetylcysteine improved alanine aminotransferase, without any difference in graft or patient survival 38. In contrast, several controlled studies found no difference in liver values compared with the control, including in MASLD, alcohol use disorder, and drug-induced liver injury 6972102107134. A meta-analysis on use after liver resection reports lower postoperative lactate, but no differences in coagulation, transfusion rate, morbidity, or length of stay 13. A meta-analysis on intravenous N-acetylcysteine in acute liver failure without paracetamol found no difference in overall survival; only in the subgroup of adults was it marginally better 23. The overall strength of evidence is low, the studies are small and differ greatly in form, dose, duration, and comparison group; for glutathione preparations in liver diseases, no controlled study is available in this area.

Further studies in this area: 74 78 80 82 85 91 94 102 107 120 134 147 154 155

NAC and Glutathione: Further Outcomes in Studies

In this area, participants were studied in numerous controlled trials and meta-analyses on very different uses of N-acetylcysteine; the evidence is strong, but the findings vary widely depending on the disease and use. Meta-analyses found lower mortality with N-acetylcysteine in COVID-19 3 as well as in cardiac catheterization procedures and heart surgeries, where contrast-induced kidney injury was also less common 2. In aluminum phosphide poisoning, a meta-analysis showed a mortality benefit only after excluding individual studies 16, and individual randomized controlled trials on poisonings found no difference in mortality 578092. In nerve damage, randomized controlled trials showed fewer neuropathy symptoms than in the control group, under paclitaxel chemotherapy 81 and in diabetic neuropathy 59. In direct comparison with dexamethasone, N-acetylcysteine relieved pain and fever after chemoembolization of the liver less strongly 62. The forms studied range from oral, nebulized, intravenous, and topical N-acetylcysteine to oral, liposomal, and intravenous glutathione. One study with vitamin C together with N-acetylcysteine found no difference in mortality after surgeries 30. It remains open for which patient groups and forms of use a benefit actually exists, since many results concern markers and the comparison groups vary greatly between studies.

Further studies in this area: 15 16 17 19 20 22 24 25 26 28 29 35 36 37 39 42 43 44 45 46 51 55 57 58 59 62 63 65 66 67 69 70 71 72 74 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 98 100 101 103 105 106 107 109 110 111 112 113 114 115 116 117 119 120 121 125 126 130 132 133 135 137 138 139 140 141 142 145 146 147 148 149 150 153 156 157

4. How Is NAC and Glutathione Dosed? Preparation, Dose and Duration in Studies

The studies used N-acetylcysteine orally, nebulized or inhaled, intravenously, and topically, as well as glutathione orally, liposomal, and intravenously. Oral, nebulized, and intravenous applications were assessed separately. Combination products with other active substances must be assessed separately and do not allow any statement about the individual substance.

5. Is NAC and Glutathione Safe? Side Effects in Studies

The studies predominantly report good tolerability of N-acetylcysteine; adverse events did not occur more frequently than with placebo in several studies 1522414750. Gastrointestinal side effects occurred more frequently with N-acetylcysteine than with placebo in individual studies 4042. In one study on intravenous N-acetylcysteine, more anaphylactoid reactions were reported 88.

6. What Remains Open: Limits of the Evidence

• Many measures are blood or cell levels and therefore markers, not clinical endpoints.
• The studies are predominantly small and short, and the comparison groups differ greatly.
• Larger controlled trials on glutathione preparations in liver diseases and mental disorders are still pending.
• For combination products, no finding applies to N-acetylcysteine or glutathione alone.
• It remains open which dose and duration are optimal for the individual diseases.

7. Bottom Line: What Is Established About NAC and Glutathione

N-acetylcysteine and glutathione intervene in oxidative metabolism. In oxidative stress and in the airways, several controlled trials show improvements in markers, lung function, and quality of life. In psychiatry and addiction, the picture is mixed: meta-analyses found advantages for depressive symptoms, obsessive-compulsive disorder, and craving, while many individual studies found no difference from placebo. In liver diseases, the picture is mixed and the evidence is weak. Many findings concern markers rather than clinical endpoints, and the studies are mostly small and short. Combination products do not allow any statement about the individual substance.