Sunday, November 18, 2012

Does Alcohol Tolerance Mean Anything? -from John in Eden Prairie, MN

Here's John's full question on alcohol tolerance: 

1)   What is the physical mechanism by which drunkenness occurs, and how does a person’s alcohol tolerance play into that?

2)   If a person with a high alcohol tolerance consumed 6 beers, and another person of similar body composition with a low alcohol tolerance consumed 6 beers, would both people’s blood alcohol content be relatively similar?  i.e. Does a person’s tolerance affect alcohol absorption in the body or does it change the person’s reaction (drunkenness) to alcohol in the body?

John, thanks for the fun alcohol question!  Your questions are all about the pharmacology and metabolism of alcohol.  First, some important points about alcohol - it is a small molecule drug that is quickly absorbed in the gastrointestinal tract, and undergoes metabolism in the liver.  People have been consuming alcohol for ages.  Alcohol is one of the first anesthetics used for surgery before the discovery of modern anesthetics.  Surgeons would get people drunk enough to pass out or be disoriented for limb amputations or the like.  Alcohol also thins the blood - so those unfortunate patients were in danger of bleeding out during those surgeries.

 Alcohol has a complicated metabolic pathway, and is broken down by numerous different enzymes to several byproducts.  "Drunkeness" occurs via alcohol's effects on the the brain - alcohol binds the opiate receptors in neurons and impacts the release and re-release of dopamine.  Heroin, cocaine, and other addictive drugs also affect the opiate receptors.  That is a common feature between drugs of addiction.  That's where the "fun" part of alcohol comes into play - euphoric feelings, boisterousness, in other words, happy drunks because of altered dopamine release.  The physical effects of alcohol - dizziness, memory loss, vomiting, headache, sleepiness or lack of sleep, etc. are also partly due to alcohol's effects on the brain.  However, the byproducts of alcohol, such as acetaldehyde and lactic acid, contribute in a big way to alcohol's unpleasant effects.  Those are the two biggies that give you a hangover, make you feel sick.  Athletes get lactic acid build-up in muscles during tough, long work-outs - and sore muscles or "hitting the wall" can result from too much lactic acid.  A night of heavy drinking can cause lactic acid build-up throughout the body, causing all those unpleasant physical effects.  Alcohol metabolism also interferes with the natural breakdown of other wastes through competition with liver resources.   Hopefully that answered your first question.

Now - about differences between people who drink similar amounts of alcohol.  The two characteristics that have the biggest impact on drunkeness are body weight and amount of food consumed prior to drinking.  Bigger people have a larger volume with which to dilute the alcohol they consume, and a full stomach slows down alcohol absorption, allowing natural alcohol metabolism to "keep up" with the rate of drinking.  Everyone gets drunk faster on an empty stomach.  Individual variations come from genetic factors or subjective experiences.  Men tend to metabolize alcohol faster than women, so a man and a woman of the same body weight, eating the same meal, drinking the same drinks, will usually result in the woman being a bit more tipsy.  Aside from that, people have genetic variations in cytochrome P450 enzymes - some of the liver enzymes involved in alcohol breakdown.  Some CYP450 variants are "fast" variants or "slow" variants.  Some people with fast CYP450 variants have to be dosed with higher amounts of prescription meds for serious illnesses.  Also, other over-the-counter drugs and even foods can stimulate CYP450 production, making your liver more or less "prepared" to metabolize alcohol.   

Alcohol flush syndrome" or more commonly "the Asian flush" is due to a mutation in acetaldehyde dehydrogenase - causing accumulation of acetaldehyde in the body.  This causes flushing of the face, neck, and other areas, and more sick feelings from alcohol consumption due to acetaldehyde build-up.  People with seemingly "high tolerance" to alcohol might be fast metabolizers, or they may have so much practice drinking that they handle the effects better.  Some people have a subjectively lower threshold for "feeling drunk" compared to others.  Other people just don't react as obviously to alcohol - "quieter, more reserved" drunks, making them appear less drunk.  Alcoholics get very adept at appearing sober when actually drunk.  They can function almost normally with a high blood alcohol content.  

Lastly, if two people of the same body weight, same body composition, same age, and same CYP450 variants ate a standardized meal (clinical speak for controlled intake) and consumed the same amount of alcohol at exactly the same time, they should achieve the same peak blood alcohol content. In reality, there are so many variables that this would be hard to compare.  And still, those two people might appear drunk differently.  

Hope this helps, John, when trying to drink others under the table.     



  1. we must be thankful for them, because despite the fact that they are always for the good of the people though they are not on the side of their family. We must be proud to them; of their hard work and courage.

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  2. Now I know why I used to get tipsy faster when I didn't take anything before drinking. Alcohol must not be that penetrating because if it is then, there will be no difference between a person who did eat prior to drinking than the one who didn't.

  3. This is sort of in response to Antoine Lockhart, but really just an interesting fact of alcohol metabolism:

    Alcohol begins being absorbed in the stomach; as a comparison, everything else you eat is absorbed in the intestines.

    In other words, alcohol is absorbed into the blood stream before any other substance you consume. 20% of the alcohol we consume is absorbed in the stomach before entering the small intestine.

  4. i took about ten different shots such Tequila, vodka, bourbon, etc in my first time and i drunk 2 Glases of beer... i threw up on my way back took about 3-4 hours before i finally threw up. i fell down and had lifted by my friends. do i have a low or high Alcohol tolerance???? i Woke up in the morning without any headache.... i threw up inside my friend's car so it was b'cuz the car or what?? btw it was my first time. I'm male and 16 yo.. I'm a lil bit confused about the headache effect that i didn't have.. can anyone answer my very curious questions??!!

    1. Its hard to tell how much tolerance you really have if you just drank a bunch back to back. That seems like a relatively normal tolerance to me. Next time I recommend drinking slower. You can still drink a decent amount, but you'll feel yourself getting sick before you actually start to throw up/pass out so you can stop.

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