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. Let's talk Tylenol Paracetamol (acetaminophen) There are many side effects that most people don't realize. OTC does not mean it is side effect free, especially with chronic use. Even just 4 days of Sex differences in glutathione metabolism and acetaminophen toxicity Tylenol's Impact on Glutathione and Liver Damage