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Health Protocols

Acetaminophen and NSAID Toxicity

What is Acetaminophen and NSAID Toxicity?

Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) (eg, aspirin, ibuprofen) are widely used as analgesics and antipyretics (fever-reducers). Overdosing on acetaminophen is not uncommon, and acetaminophen accounts for up to 50% of all adult cases of acute liver failure in the United States.

Acetaminophen can be toxic to the liver and kidneys. Excess levels overwhelm the liver’s innate detoxification system by depleting levels of glutathione, the ubiquitous cellular antioxidant. Acetaminophen overdose can cause acute liver failure, and in some cases, renal failure.

NSAIDs can cause toxicity in the gastrointestinal tract, kidneys, and cardiovascular system. Their risk profiles vary depending on their cellular targets.

Natural interventions such as N-acetylcysteine and silymarin may help prevent acetaminophen and NSAID toxicity.

What are Risk Factors for Acetaminophen and NSAID Toxicity?

  • Aging
  • Renal or hepatic impairment (and other pre-existing medical conditions)
  • Alcohol use
  • Concurrent use of certain medications
  • Malnutrition

Note: Always read dosing instructions and warnings on every medication. For an adult, the maximum recommended single dose of acetaminophen is 1 gram and the maximum dose in a 24-hour period is 4 grams. Pay specific attention if you are taking more than one medication—many contain acetaminophen and inadvertent combination can easily cause an overdose.

What are Signs and Symptoms of Acetaminophen and NSAID Toxicity?


  • Nausea, vomiting
  • Tenderness/pain in upper right abdomen
  • Jaundice
  • Impaired consciousness

Note: If you suspect an acetaminophen overdose immediately call 911 or the National Poison Control Center (1-800-222-1222).


  • Heartburn
  • Nausea
  • Abdominal pain

What are Conventional Medical Treatments for Acetaminophen and NSAID Toxicity?

Acetaminophen overdose:

  • N-acetylcysteine, administered either intravenously or orally, to restore glutathione levels
  • Activated charcoal to absorb excess drug
  • If acute liver failure occurs, intensive supportive therapy or liver transplantation may be required

NSAID toxicity:

  • Gastroprotective agents to prevent or treat gastric ulcers (eg, proton pump inhibitors [eg, omeprazole])

What are Emerging Therapies for Acetaminophen and NSAID Toxicity?

  • Combining NSAIDs with gastroprotective agents in single-tablet formulations
  • Topical NSAIDs

What Natural Interventions May Be Beneficial for Acetaminophen and NSAID Toxicity?

  • N-acetylcysteine (NAC). High dose NAC is a conventional treatment for acetaminophen overdose. Taking at least 600 mg NAC anytime acetaminophen is used may help prevent liver toxicity.
  • Methionine. Methionine, a precursor to glutathione and other cellular antioxidants, may be used as an alternative to NAC.
  • S-adenosylmethionine (SAMe). Levels of SAMe, a derivative of methionine, are decreased in the presence of acetaminophen. One animal study showed comparable efficacy of SAMe and NAC after acetaminophen overdose.
  • Selenium. Selenium is a cofactor for enzymes that synthesize glutathione and detoxify acetaminophen. Selenium deficiency may decrease the acetaminophen dose necessary to produce toxicity, and coadministration with NAC may be more effective than NAC alone.
  • Carotenoids. Several carotenoids, including lutein and lycopene, have been shown in animal models to exert protective effects against acetaminophen toxicity.
  • Silymarin. Silymarin, a mixture of compounds from milk thistle, has been shown to protect against acetaminophen toxicity and may be more effective than NAC if treatment is delayed after overdose.
  • Other natural interventions that may protect against acetaminophen toxicity include curcumin, polyphenols such as resveratrol and green tea extract, coenzyme Q10, several botanicals such as Ginkgo biloba and garlic, and others.
  • Natural interventions such as zinc-carnosine, licorice, and Boswellia serrata may protect against the gastrointestinal side effects of NSAIDs.