Tylenol/Acetaminophen: NAC Is The Antidote To Its Toxic Glutathione Depleting Effects

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Along with providing information on whether N-Acetyl Cysteine (NAC) supplements might be right for you, this article also links to Fullscript where you can buy high quality supplements. Order online through Fullscript’s secure healthcare formulary to get the best prices and free shipping on professional-grade supplements.

Tylenol, known generically as acetaminophen, is a widely used over-the-counter medication for relieving pain and reducing fever. Unlike NSAIDs, acetaminophen does not significantly reduce inflammation but works by inhibiting the brain’s chemicals that signal pain and by affecting the body’s temperature regulation center.

About Acetaminophen and Glutathione

If you take more than one medicine at a time that contains acetaminophen, it increases your chance of going above the 4,000 mg per 24 hours limit, which could harm your liver.  More than 500 medicines * contain acetaminophen, including prescription and OTC medicines for back pain, headache, sleep, and cold and flu symptoms. 

Acetaminophen is well known for its ability to damage the liver. The combination of acetaminophen and a damaged liver increases the risk that glutathione will be depleted and toxic metabolites will further damage the liver. 

NAC May Improve Pain-Relieving Effects of Acetaminophen

In animal models, NAC has been shown to improve acetaminophen’s pain-relieving effects. [*] Some clinical trails also showed evidence that NAC may provide pain relief, although this effect is not consistent. [*] Taking acetaminophen depletes glutathione, “the master antioxidant” that detoxifies the toxic breakdown products of acetaminophen. Taking N-Acetyl-Cysteine (NAC) restores glutathione.

Acetaminophen Drug-Nutrient Interactions:

  • Glutathione: Glutathione supplements can benefit acetaminophen users by replenishing the body’s primary antioxidant, protecting the liver from potential damage caused by prolonged or excessive acetaminophen use through detoxification and reducing oxidative stress. /PMC4684116
  • N-Acetyl Cysteine: NAC is a rate-limiting precursor for the synthesis of glutathione. NAC supplements can raise the body’s production of glutathione, a crucial antioxidant for liver protection, and serve as an antidote to acetaminophen overdose by reducing liver toxicity and improving detoxification processes. /PMID: 26602168
  • Alcohol: Combining acetaminophen with alcohol significantly raises the risk of liver damage, emphasizing the importance of avoiding this mix. /PMID: 18486561, /PMID: 33333080
  • Caffeine: Some evidence suggests that caffeine may increase the pain-relieving effects of acetaminophen. /PMID: 17442681 However, this combination should be approached with caution, as excessive caffeine can also have adverse effects.
  • Chronic high-dose acetaminophen use: may deplete glutathione, an antioxidant that is crucial for detoxifying the liver. This depletion can leave the liver more vulnerable to damage from acetaminophen and other toxins. /PMID: 12911681, /PMC1434362

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NAC by Integrative Therapeutics

N-Acetyl L-Cysteine (NAC) helps to replenish intracellular glutathione, which is vital in cellular antioxidant pathways.*

Suggested Use: Take 1 capsule once or twice daily, or as recommended by your healthcare professional.


Amount Per 1 Capsule Serving

N-Acetyl L-Cysteine (NAC) … 600 mg**


To Sum It Up

Tylenol has the potential to deplete glutathione. N-Acetylcysteine (NAC) supplements can be a great help for people who regularly take Tylenol (acetaminophen) for pain or fever. NAC raises glutathione, the body’s main protective antioxidant, helping protect the liver from damage that can happen if too much Tylenol is used. It’s especially helpful if too much Tylenol is taken by mistake, acting as a safety net for the liver. This summary highlights how NAC supplements can support liver health for those who depend on Tylenol, emphasizing the importance of considering supplements that can make using common over-the-counter medications safer and more effective.


This Article is Not a Substitute for Medical Advice

This information is provided for educational purposes only and is not a substitute for medical advice. Supplement Sciences does not provide medical care and cannot ensure the safety or effectiveness of any product for your personal use. Always consult your physician before starting any supplement, especially if you are pregnant, breastfeeding, or managing a serious health condition such as cancer, liver disease, or kidney disease. Dietary supplements are not designed to diagnose, treat, cure, or prevent any disease.


About the Author

Supplement Sciences

This article is created by the Supplement Sciences writing team. It is reviewed for medical and nutritional accuracy by Stephanie Figon, MS, RDN, LD. Please let us know your thoughts by messaging us at reviews@supplement-sciences.com.

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