Glycine
Three grams before bed, tastes faintly sweet, costs almost nothing, and has a plausible mechanism for better sleep quality — on a thin trial base.
3 g before bed
C Mixed or limited evidenceSleep
General Health
N-Acetylcysteine
Also known as: NAC, acetylcysteine, glutathione precursor
A hospital antidote with a genuine psychiatric research literature behind it — and a supplement aisle full of claims that literature does not support.
Grade CMixed or limited evidence
Studied dose600-1,800 mg/day; psychiatric trials typically used 2,400 mg
TimingBetween meals absorbs slightly better, …
EvidenceGrade C
CategoryGeneral Health
Established medicine for paracetamol overdose and mucus clearance. Psychiatric trials — trichotillomania, OCD-spectrum behaviours, addiction — show promise but are small and inconsistent. General antioxidant and longevity claims are unsupported.
NAC is a real drug that ended up on supplement shelves, and the gap between its two lives is instructive.
In a hospital it is unglamorous and indispensable: the antidote for paracetamol overdose, where it restores the glutathione that the drug's toxic metabolite depletes and prevents liver failure. It is on the WHO Essential Medicines List for that reason. It is also a decent mucolytic, breaking disulphide bonds in mucus, and there is reasonable evidence it reduces COPD exacerbations.
The more interesting literature is psychiatric, and it stems from the glutamate mechanism rather than the antioxidant one. NAC restores glutamate homeostasis in the nucleus accumbens, and clinical trials have followed that lead into compulsive and addictive behaviour. Trichotillomania — compulsive hair-pulling — has the most convincing result, with a well-conducted RCT showing substantial improvement. Skin-picking, some OCD presentations, and cannabis and cocaine dependence have positive but inconsistent findings, and there are trials in bipolar depression and schizophrenia with mixed outcomes. This is a genuine research programme rather than supplement marketing, and it is also nowhere near settled.
What does not hold up is the general case. "Boost your glutathione" reads well on a label, but antioxidant status in a healthy adult is not a deficiency waiting to be corrected, and chronically blunting oxidative signalling may be actively counterproductive — the same lesson high-dose vitamin C and E supplementation taught in exercise trials, where it reduced training adaptations. There is no good evidence that NAC extends healthspan in humans.
One regulatory oddity worth knowing: because NAC was approved as a drug before it was sold as a supplement, the FDA has periodically challenged its status as a dietary supplement, which is why availability has wobbled in the US. That is a legal argument about precedence, not a safety finding.
If you have a specific indication with trial support, 600-1,800 mg daily divided is reasonable, and psychiatric uses need two to three months before judging. Otherwise the case is weak.
How it works
NAC supplies cysteine, the rate-limiting amino acid for synthesising glutathione, the body's principal intracellular antioxidant. Separately and probably more relevantly to its psychiatric effects, it modulates glutamate transmission via the cystine-glutamate antiporter, which is thought to underlie its results in compulsive and addictive behaviour.
What the evidence supports
- Prevents liver injury in paracetamol overdose established emergency medicine, not a supplement useA
- Reduces compulsive hair-pulling and skin-picking best-supported psychiatric indication; 8-12 weeks to effectB
- Reduces COPD exacerbations and clears mucus mucolytic action; benefit concentrated in chronic bronchitisB
- Improves general health or longevity via glutathione no human evidence; chronic antioxidant loading may blunt adaptationD
Safety
Well tolerated orally. The notable caution is asthma — NAC can occasionally trigger bronchospasm. It has mild antiplatelet activity, and its sulphur content produces an unpleasant smell and, in some people, nausea. Do not take it alongside activated charcoal, which adsorbs it.
Reported side effects
- Nausea, vomiting, and a sulphurous smell
- Rare bronchospasm, particularly in asthma
- Headache
Interactions
- Additive bleeding risk with anticoagulants and antiplatelet drugs.
- May potentiate nitroglycerin, causing headache and hypotension.
- Activated charcoal adsorbs NAC and blocks it.
This guide is educational, not medical advice. Talk to a physician or pharmacist before starting any supplement, especially alongside prescription medication or a medical condition.
Common questions
- What does N-Acetylcysteine do?
- A hospital antidote with a genuine psychiatric research literature behind it — and a supplement aisle full of claims that literature does not support. Its best-supported effects are prevents liver injury in paracetamol overdose and reduces compulsive hair-pulling and skin-picking.
- Does N-Acetylcysteine actually work?
- Mixed or limited evidence (grade C). Established medicine for paracetamol overdose and mucus clearance. Psychiatric trials — trichotillomania, OCD-spectrum behaviours, addiction — show promise but are small and inconsistent. General antioxidant and longevity claims are unsupported.
- How much N-Acetylcysteine should I take?
- The studied range is 600-1,800 mg/day; psychiatric trials typically used 2,400 mg, divided into 2-3 doses. Start at the low end — more is not better once the effective range is covered.
- When should I take N-Acetylcysteine?
- Between meals absorbs slightly better, but with food if it upsets your stomach. Psychiatric effects take 8-12 weeks to appear — this is not an acute compound.
- Is N-Acetylcysteine safe?
- Well tolerated orally. The notable caution is asthma — NAC can occasionally trigger bronchospasm. It has mild antiplatelet activity, and its sulphur content produces an unpleasant smell and, in some people, nausea. Do not take it alongside activated charcoal, which adsorbs it. The most reported side effects are nausea, vomiting, and a sulphurous smell, rare bronchospasm, particularly in asthma, headache.
- What should you not mix N-Acetylcysteine with?
- Additive bleeding risk with anticoagulants and antiplatelet drugs. May potentiate nitroglycerin, causing headache and hypotension. Activated charcoal adsorbs NAC and blocks it. Ask a pharmacist or physician before combining it with prescription medication.
References
Evidence review last updated