Yes there is good evidence that acetaminophen (the active ingredient in Tylenol) can deplete glutathione under certain conditions. But whether that matters depends on dose, duration, and individual factors. Acetaminophen metabolism Full article: Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease Haggling with HAGMA: A Common Medication with an Uncommon Differential Renal Fellow Network How do glutathione and Nacetylcysteine (NAC) compare regarding indications, dosing, effectiveness, and safety for acetaminophen toxicity, mucolytic therapy, and general antioxidant supplementation?