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I can understand natural variation in alcohol dehydrogenase (ADH) in a population leading to variation in rate of inebriation (after controlling for other variables -- e.g., mass, food consumption, etc.).

But what physiological (adaptive?) process leads to increased alcohol tolerance over the long term in a single individual?

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Are you asking about individual variability in alcohol tolerance or you mean the characteristical symptome of the Alcoholistm II: increase of alcohol tolerance? –  Alexander Galkin Jan 5 '12 at 12:31
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[Untested] If I have 1-2 drinks per day 3-4 times a week. Assuming all other factors are equal, after some period of time (months?), I will be able to drink 3-4 on one day without feeling inebriated. How does this adaptive tolerance work? –  kmm Jan 7 '12 at 17:35
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The subject of alcohol tolerance is broader than it might appear. However, in most cases people refer to what is called metabolic alcohol tolerance. Based on your response to the comment made by Alexander Galkin, I assume that you also refer to metabolic alcohol tolerance.

Metabolic alcohol tolerance is the result of drinking significant amounts of alcohol over a period of time as you describe. Both the amount of alcohol and the duration that it takes to develop an increased metabolic tolerance towards alcohol differ from person to person.

When most people drink alcohol, the liver will responds by activating alcohol degrading enzymes that break down the alcohol molecules, which results in the elimination of the intoxicating effect. The activation of those enzymes occurs much faster with people who have developed metabolic alcohol tolerance and the concentration of those enzymes is generally higher. This means that those people can break down alcohol faster than you and me, that is, they can "tolerate" more alcohol in the sense that they simply get rid of it much quicker.

On a final note, being more alcohol tolerant is not exactly correct as metabolic tolerance doesn't necessarily mean that the organs affected/intoxicated (such as the brain) by alcohol aren't necessarily more tolerant. The alcohol is simply broken down much faster and can therefore have a limited impact.

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So, judging by your answer to my comment you are most likely talking about so-called consumption-induced alcohol tolerance, that one might develop by regular drinking of alcoholic beverages.

We can group the reasons for increased tolerance to the following groups: better adaptation for the elevated concentrations (functional) or increased break-down (metabolic).

Functional tolerance.

This means that your body and its organs, especially your CNS, adapt to compensate for the increased alcohol concentration and manage to sustain its functioning despite the elevated blood alcohol concentrations (BAC). So, the dose of alcohol which previously led to trembling and disorientation now evokes only some coordinatory disturbances.

The physiological mechanisms involved here are: 1. Desensitization of the alcohol-sensitive (primarily GABA-ergic) receptors in CNS. 2. Changes in the neuron firing rates (to compensate for the deterioration of the GABA-ergic inhibition).

Metabolic tolerance.

This condition is characterized by the increased alcohol break-down by the liver, that slows down the increase of blood alcohol concentration (BAC) upon its consumption leading to the attenuation or complete disguise of alcohol intoxication (inebriation).

The main enzyme that is responsible for alcohol transformation is the so-called alcohol dehydrogenase (ADH), that represents a group of substances catalyzing the alcohol oxidation to aldehydes. This enzymes are located in the liver cells (hepatocytes) and the increase in their activity (and most likely also the absolute amount) is not well understood. It happens, by the way, not only on alcohol consumption: the intake of barbiturates also leads to the increase of ADH and tolerance.

Here you can find much more information about acquired alcohol tolerance, but mostly from the behavioural viewpoint.

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