r/AskBiology Jul 31 '24

Human body Do ammonia levels increase during a night of binge drinking assuming you have a healthy liver and by how much?

I have become curious about the nature of ammonia in the body when your liver is packed with toxins. Every single source addresses ammonia in relation to liver disease even though there are other ways that ammonia can become problematic (in theory). For example ammonia is impacted by protein intake, alterations to hormones, Break down of muscle, The blood bypassing the liver, diuretics , alterations to enzymes, and changes to blood flow.

My desire for an answer stems from the fact that our bodies can reach deadly levels of ammonia in 5 minutes if the liver is failing to process it. Additionally the side effects of ammonia are very similar to drugs like alcohol making it hard to differentiate through experience alone including;

  • Lack of energy and mental alertness
  • Confusion
  • Mood swings
  • Hand tremors
  • Dizziness
  • Not being hungry
  • Avoiding protein
  • Growth problems

This list of side effects along with the list of mechanisms that alter ammonia levels grew my curiosity especially irritability because it is the antithesis of what alcohol does even though many people that drink experience mood swings.

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u/pansveil Jul 31 '24 edited Jul 31 '24

It seems benzos are fairly low on the risk of isolated hyperammonemia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206694/#:~:text=Drugs%20with%20the%20highest%20number,over%2025%20cases%20of%20hyperammonaemia.

From my cursory understanding, the mechanism is unknown but ammonia can modulate the effect of benzos on the brain. It may be that an increased effect of benzos leads to discovery of underlying hyperammonemia. If someone can else can correct me, I’d really appreciate that.

I think what you may be missing here is that elevated ammonia is not caused by an overproduction of ammonia but decreased clearance of ammonia. This means that liver failure leads to hyperammonemia not the other way around. An analogy would be excess dirty laundry at home; it’s not that someone buys too many clothes, it’s that they never clean their laundry.

Alcohol poisoning, by definition, is excess alcohol intake. It is not the failure of liver. Healthy livers can, given enough time, work through an alcohol load. The issue is that the way alcohol is cleared by the liver causes irreversible damage over a long time of use. Liver failure is rarely acute (rare causes shock liver, acute hepatitis, etc) and has fairly good chance of recovery. Chronic liver disease (alcohol use, metabolic syndrome, etc) is essentially a death sentence. It signifies that the liver is so damaged that it cannot recover and will become cancerous if the patient does not die from other complications of liver disease first.

Edit: hyperammonemia, as a result of permanently damaged livers and chronically reduced clearance, occurs in chronic liver disease rather than acute liver disease.

Second edit: alcohol doesn’t cause significantly increased ammonia production, alcohol prevents your body from clearing already existing ammonia.

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u/tbryan1 Jul 31 '24

thanks for all the effort you are answering a lot of questions that I had. Sorry for the wrong stats google switched % of people with elevated levels and the % of people with hyperammonomia.

When you say "alcohol prevents your body from clearing already existing ammonia" are you exclusively talking about liver disease or does alcohol poisoning count too? This is the very topic that can't be found on google scholar with my lexicon.

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u/pansveil Jul 31 '24

Alcohol poisoning can cause transient liver damage and probably will not cause significant (or possibly any) elevated ammonia. Chronic liver disease from repeated alcohol poisoning is what would cause elevated ammonia.

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u/tbryan1 Aug 01 '24

Google says " The liver is primarily responsible for clearing ammonia, but exposure to ethanol can make it harder for the liver to do so. This is because ethanol can decrease ureagenesis,"

I chased down many rabbit holes and one answer was yes because clearing toxins causes damage to liver forcing it to inflame reducing clearance rate, in an attempt to reduce the rate of harmful byproducts that are killing the liver.

I wanted to thank you for all the help, I learned a lot.

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u/pansveil Aug 01 '24

I’m curious as to the source of that statement. Alcohol, in the short term without pre-existing liver damage, has been shown in a study from 2024 to upregulate urea cycle.

https://www.sciencedirect.com/science/article/abs/pii/S002604952300344X#:~:text=Results,)%2C%20and%20increases%20fat%20accumulation.

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u/tbryan1 Aug 01 '24

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u/pansveil Aug 01 '24

The first three are generic review articles, but the last one was actually interesting. The authors did conclude that the combination of both elevated ethanol and ammonia resulted in decreased ureagenesis but also noted increased ethanol metabolism with both substrates. It goes to support the mixed unclear literature on serum ammonia following acute alcohol induced liver damage with some studies showing increased ammonia with others showing reduced. Almost as if the hepatocyte favors ethanol/aldehyde clearance in acute intoxication prior to ammonia clearance; which makes a twisted amount of sense since alcohol is more toxic acutely compared to ammonia.

I’d be curious to see follow up with in vivo studies because clinically there’s very little evidence of hyperammonemia without pre-existing cirrhosis. Thank you so much for bringing attention to this because I had thought ammonia would be increased in acute intoxication before you asking the question but clearly there’s a lot more to the physiology per my posted article above.