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Alcohol and Tylenol Can Be a Deadly Combination

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.[1],[2],[3]

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.[4]

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.[5],[6]

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.[7]

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.[8]

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).[9],[10],[11],[12]

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.[13],[14]

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
  • Magnesium
  • 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[15]
  • 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![16]
  • Resting in a dimly-lit setting, or wearing an eye mask




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The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.

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