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. The parent compounds of acetaminophen (US market in 1955 in the US as Tylenol and other products) were first discovered in 1886 (acetanilide) and 1887 (phenacetin). These were the earliest synthetic fever Do You Reach for Tylenol Often? Whether it's for pain, headaches, or fever Tylenol (acetaminophen) is one of the most commonly used medications. But here's something most people don't realize View of Acetaminophen, the missing anion gap in the patient with metabolic acidosis The Southwest journal of medicine Acetaminophen metabolism