The sulfur amino acid that usually limits how much glutathione you can make. NAC, its supplement form, has real clinical uses.
Mechanisms, studies and evidence grades for each claim above.
Cysteine is the sulfur-donating partner in glutathione synthesis (glutamate + cysteine + glycine → glutathione), and is generally considered the rate-limiting substrate in that pathway — its thiol (–SH) group is the business end of glutathione's antioxidant chemistry. The body makes cysteine from methionine via the transsulfuration pathway, which is why it's classed as conditionally essential. See Glutathione, Methionine and Glycine / Collagen. (Strong — biochemistry)
Free cysteine is unstable and oxidizes easily, so the supplement form is N-acetylcysteine (NAC), which the body deacetylates back to cysteine. Oral NAC's systemic bioavailability is low — most is metabolized in the gut wall and liver on first pass1 — which is part of why its effects are more convincing as a glutathione precursor than as a direct antioxidant.
↑ back to summaryThe clearest proof that cysteine supply limits glutathione. In overdose, acetaminophen (paracetamol) is metabolized to a reactive intermediate, NAPQI, that is normally neutralized by glutathione. Once hepatic glutathione runs out, NAPQI binds liver proteins and destroys hepatocytes. NAC, given promptly, replenishes glutathione and is the standard antidote worldwide.2 This is a hospital treatment, not a reason to take NAC with Tylenol. (Strong)
↑ back to summaryNAC also thins mucus by breaking disulfide bonds in mucus proteins. In PANTHEON, 1,006 Chinese patients with moderate-to-severe COPD took 600 mg NAC or placebo twice daily for a year: exacerbations fell from 1.49 to 1.16 per patient-year (risk ratio 0.78, p=0.001), with side effects no different from placebo.3 Note the funder: the trial was sponsored by Hainan Zambon, a manufacturer of NAC. (Moderate — large RCT, industry-funded, single country)
↑ back to summaryNAC feeds the cystine–glutamate antiporter, which modulates extracellular glutamate in the nucleus accumbens — a reward-circuit mechanism proposed to dampen compulsive behavior. In a 12-week double-blind trial in 50 adults with trichotillomania (compulsive hair-pulling), NAC at 1,200–2,400 mg/day produced "much or very much improved" ratings in 56% versus 16% on placebo (p=0.003), with no adverse events; improvement appeared after about 9 weeks.4 Trials across other compulsive and addictive conditions have been more mixed. (Early — one positive RCT in this indication)
↑ back to summaryGlutathione falls with age, and both of its limiting precursors — cysteine and glycine — are implicated. In a randomized trial, 24 older adults took GlyNAC (glycine + NAC) or an alanine placebo for 16 weeks, with 12 young adults as a reference group. GlyNAC, but not placebo, corrected glutathione deficiency and improved oxidative stress, mitochondrial fat oxidation, inflammation, insulin resistance, endothelial function, gait speed, strength, waist circumference and blood pressure.5 That's an unusually long list of wins from 12 treated people — worth taking seriously as a hypothesis, and worth replicating before believing in full. (Early — small RCT, needs replication) It pairs directly with the glycine argument on the Glycine / Collagen page.
↑ back to summaryDietary protein generally supplies enough cysteine; low availability is typically seen with broader malnutrition or illness rather than as an isolated deficiency. There's no RDA for cysteine alone; it's covered within the combined sulfur amino acid (methionine + cysteine) requirement.