Acetaminophen carries a risk of hepatotoxicity; what lifestyle factor worsens this risk?

• A. Alcohol use.
• B. High-fat diet.
• C. Sleep deprivation.
• D. Exercise.

Answer: (A)

Alcohol use increases the risk of acetaminophen-induced liver injury because it boosts the production of the toxic metabolite NAPQI and depletes the liver’s glutathione stores, weakening the detoxification pathway. Acetaminophen is normally processed in the liver, and a portion is converted to NAPQI, which is highly reactive. Glutathione typically neutralizes NAPQI, preventing damage. Chronic or heavy alcohol use induces liver enzymes (like CYP2E1) that generate more NAPQI and often lowers glutathione reserves, so more NAPQI can accumulate and harm liver cells. This makes alcohol consumption the lifestyle factor that worsens hepatotoxic risk with acetaminophen. The other options don’t directly impact the acetaminophen metabolic pathway in a way that increases this risk.