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.