Alcohol and Tylenol Can Be a Deadly Combination
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Why taking acetaminophen (paracetamol) for a hangover is a dangerous idea.
The over-the-counter pain medication acetaminophen is a surprisingly controversial drug. Sold under the brand name Tylenol in North America and known as paracetamol in other countries, acetaminophen can be taxing to the liver. Acetaminophen is the number one cause of acute liver failure in the West.,,
The risks of liver damage, liver failure, and death go way up when the drug is combined with alcohol. That’s because alcohol prevents the liver from quickly detoxifying acetaminophen. This allows toxic intermediary metabolites released during the breakdown of acetaminophen to build up and harm the liver.
The liver metabolizes drugs in two phases: Phase 1 and Phase 2. In Phase 1 detoxification, enzymes convert drugs and toxins into intermediate forms. These intermediate substances then go on to Phase 2 for processing. In Phase 2, conjugation makes the intermediary metabolites less harmful to the body. The metabolites are then made water-soluble (able to dissolve in water), so they can easily pass out of the body through the urine and feces.,
Alcohol prevents the liver from quickly detoxifying acetaminophen.
When a healthy, sober person takes acetaminophen, their liver begins the work of breaking down the drug. The acetaminophen passes through Phase 1 detoxification and is turned into an intermediate metabolite called N-acetyl-p-benzoquinone imine, or NAPQI. Although NAPQI is toxic, only tiny amounts of NAPQI are produced, and then are almost immediately neutralized in Phase 2 with the help of the antioxidant glutathione. All that remains after Phase 2 is a non-toxic substance that’s filtered by the kidneys and excreted out of the body.
When there’s alcohol in the body, however, the detoxification of acetaminophen isn’t so clean cut. Alcohol is known to enhance up Phase 1 detoxification in the liver and decrease Phase 2. This a harmful double-punch, as Phase 1 detoxification converts acetaminophen into the toxic metabolite NAPQI. With Phase 2 being slowed down, NAPQI starts building up in the livers of people who have been drinking.
The liver needs a good supply of glutathione to turn that toxic NAPQI into a harmless substance in Phase 2. Unfortunately, however, alcohol depletes glutathione stores, sabotaging Phase 2 detoxification and further contributing to the buildup of toxic NAPQI. Regular drinkers tend to have even lower glutathione levels, placing them at even greater risk of NAPQI buildup. (Curiously, however, alcoholics are at greatest risk of acetaminophen-related toxicity within their first few days of sobriety).,,,
Alcohol depletes glutathione stores, sabotaging Phase 2 detoxification.
As mentioned earlier, NAPQI is toxic to the body. As it builds up in the liver, it causes damage to the liver cells (hepatocytes), and can even kill them. This injury can not only cause acute liver failure (a medical emergency), but also death. In fact, many cases of acute liver failure are caused by combining alcohol with acetaminophen.,
Many cases of acute liver failure are caused by combining alcohol with acetaminophen (paracetamol).
Healthier hangover remedies
If you find yourself nursing a hangover this holiday season, skip the acetaminophen. Some healthier strategies for dealing with hangovers can include:
- Staying hydrated with water, electrolytes, bone broth, and/or green juice
- Eating some protein (even if you’re not hungry) to balance blood sugar levels and curb nausea
- B vitamins
- Milk thistle and other liver-loving supplements
- N-acetyl cysteine (NAC) – which increases glutathione production, and can also be an antidote to acetaminophen poisoning
- Getting some fresh air, going for a gentle walk
- Smelling peppermint oil and applying it to the temples – one study showed it worked as well as acetaminophen for headaches!
- Resting in a dimly-lit setting, or wearing an eye mask
ReferencesClick here to see References
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 Woolbright BL, Jaeschke H. Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure. J Hepatol. 2017 Apr;66(4):836-48.doi: 10.1016/j.jhep.2016.11.017.
 “Acute liver failure.” Mayo Clinic [Internet]. Accessed December 10, 2021. Available at: https://www.mayoclinic.org/diseases-conditions/acute-liver-failure/symptoms-causes/syc-20352863
 Draganov P, et al. Alcohol-acetaminophen syndrome. Even moderate social drinkers are at risk. Postgrad Med. 2000 Jan;107(1):189-95. doi: 10.3810/pgm.2000.01.831.
 Black M, Raucy J. Acetaminophen, alcohol, and cytochrome P-450. Ann Intern Med. 1986 Mar;104(3):427-9. doi: 10.7326/0003-4819-104-3-427.
 Grant DM. Detoxification pathways in the liver. J Inherit Metab Dis. 1991;14(4):421-30. doi: 10.1007/BF01797915.
 Hedgpeth B, et al. A review of bioinformatics tools to understand acetaminophen-alcohol interaction. Medicines (Basel). 2019 Jul 25;6(3):79. doi: 10.3390/medicines6030079.
 McClain CJ, et al. Potentiation of acetaminophen hepatotoxicity by alcohol. JAMA. 1980;244(3):251-3. doi:10.1001/jama.1980.03310030027020.
 Videla LA, Valenzuela A. Alcohol ingestion, liver glutathione and lipoperoxidation: metabolic interrelations and pathological implications. Life Sci. 1982 Nov 29;31(22):2395-407. doi: 10.1016/0024-3205(82)90743-3.
 Puri P, et al. Alcohol consumption is associated with the severity and outcome of acute liver injury/failure. Liver Int. 2020 Feb;40(2):360-7. doi: 10.1111/liv.14327.
 Krähenbuhl S, et al. Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage. Digestion. 2007;75(4):232-7. doi: 10.1159/000111032.
 Riordan SM, Williams R. Alcohol exposure and paracetamol-induced hepatotoxicity. Addict Biol. 2002 Apr;7(2):191-206. doi: 10.1080/13556210220120424.
 Bunchorntavakul C, Reddy KR. Acetaminophen (APAP or N-Acetyl-p-Aminophenol) and acute liver failure. Clin Liver Dis. 2018 May;22(2):325-46. doi: 10.1016/j.cld.2018.01.007. Epub 2018 Feb 9.
 Chu A. “Can I drink alcohol with Tylenol?” GoodRx Health [Internet]. Dec 3, 2021. Accessed Dec 10, 2021. Available at: https://www.goodrx.com/acetaminophen/tylenol-and-alcohol
 Larson Anne M. Acetaminophen hepatotoxicity. Clin Liver Dis. 2007 Aug;11(3):525-48. doi: 10.1016/j.cld.2007.06.006.
 Göbel H, et al. Peppermint oil in the acute treatment of tension-type headache. Schmerz. 2016 Jun;30(3):295-310. doi: 10.1007/s00482-016-0109-6.
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Dr. Erica Zelfand
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