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. 1. Widespread Use of Acetaminophen ATrain Education Acetaminophen toxicity EMCrit Project Sex differences in glutathione metabolism and acetaminophen toxicity A Possible Antidote for Tylenol (Paracetamol) Overdose American Council on Science and Health Acetaminophen Overdose Reveals PAR4 as a Low Expressing but Potent Receptor on the Hepatic Endothelium in Mice Arteriosclerosis, Thrombosis, and Vascular Biology