Oh God Never Again....

[Rolanbek]

Oh God never again…

We have all been there, head throbbing, gasping for water, with your stomach threatening to rebel at any moment. The demon drink having overwhelmed our self control the night before, now wrecking hangover havoc from our first waking moment.
Along with the attendant impurities in and the dehydrating effects of alcohol, comes a chemical that is also a visitor to our delicate “morning after” metabolisms: Acetaldehyde.
Formed during the breakdown of ethanol in the liver, and known since the early 80’s to be many times more toxic to us than ethyl-alcohol itself, Acetaldehyde rampages through every organ in the body and denaturing many proteins via adduct formation, especially those of skeletal muscles. In is worth remembering that DNA, being composed of protein pairs, is also vulnerable and this raises the spectre of Carcinogenesis in Acetaldehyde’s repertoire.
While dodging drink might help avoid these toxic by products it has been found that many other human activities add to our Acetaldehyde load. Yoghurt producers in particular attempt to increase the level of acetaldehyde in their products because it enhances the fruity flavour of their product. Cigarette smoke and engine fumes contain it but we already knew that very little good would come of inhaling either. One of the more surprising sources of Acetaldehyde is bacteria in the mouth, similar in their biochemical output to those bacteria that the diary industry use, one particular bacterium streptococcus salivarius is a veritable factory for the stuff.
In short exposure to this chemical is a daily occurrence, but to limit your exposure, keep your teeth clean, reduce your exposure to tobacco smoke and petrol fumes and try not to pummel your liver into submission every night.

Do you want to know more?

R

[wilpuri]

"The hangover itself is not the worst part, the real pain begins when last night's unavoidable truths begin to gradually reveal themselves."
-Arne Anka

[Niles Crane]

Come back to me when they've found a cure for it.

[Ummon]

Come back to me when they've found a cure for it.

There is no natural enzyme capable of digesting acetaldehyde into non-toxic compounds (when there is a high intracell concentration of ethanol, obviously).

[Niles Crane]

There is no natural enzyme capable of digesting acetaldehyde into non-toxic compounds (when there is a high intracell concentration of ethanol, obviously).

Then why not create an artificial enzyme?

[Ummon]

Probably the reaction is difficult to orient the other way around. In any case, it's not clear what is possible, and what will be.

[Rolanbek]

pretty much every tissue in the body has enzymes to deal with the break down of acetaldehyde. Acetaldehyde dehydrogenases (ALDH) of which there are 19 different varieties currently known, convert Acetaldehyde into relatively harmless acetic acid.

ALDH2 is the enzyme which does the most work in this respect, and curiously is nonfunctional in a high percentage of the Japanese and Chinese populations. Around 50% of those populations have inherited a dominant non fuctional version of this gene, and this versions presence can be identified by "flushing" almost immediately when alcohol is imbibed, and a low tolerence for alcohol.

R

[Ummon]

The rate of conversion (to acetic acid) is not proportional to the rate of formation (of acetaldehyde), because the acetic acid is not eliminated (the enzyme is saturated). That's the why of the part within the brackets.

These enzymes, differently from the MEOS, cannot be induced, as well, if I remember correctly.

The concentration of acetic acid, rapidly rising and accumulating after alcohol usage, blocks the reaction, thus making for the effects of alcohol.

That is also why you should avoid consuming vinegar and ethanol together.

[Rolanbek]

True, but not really relevent to my comment regarding this:

There is no natural enzyme capable of digesting acetaldehyde into non-toxic compounds (when there is a high intracell concentration of ethanol, obviously).

Which is a false statement.

ALDH's are natural and Acetic acid is largely a non-toxic by-product.

R

[The Fish]

It's also the reason why chronic alcoholics often don't respond well to certain drugs. The constant drinking of alcohol ramps up the MEOS system (basically variants of cytochrome P-450 in the smooth ER of these patients) resulting in increased hepatic clearance ("first-pass effect") of the pharmacological agents, and therefore lower therapeutic doses. After a while, though, the trend reverses itself; eventually the liver gets cirrhosis and hepatic clearance actually decreases, making the danger of toxic levels of drugs much greater.

As an aside, since the issue of hangovers has come up, DO NOT take acetaminophen (i.e. Tylenol) for a post-hangover headache. Tylenol is converted in the liver to a toxic byproduct that is conjugated with a molecule called glutathione and excreted. Alcohol detoxification by the liver also requires glutathione, and thus drinking a lot can deplete this molecule. If subsequently acetaminophen is taken, the toxic byproduct floats around the liver in its unconjugated form, and can lead to serious liver damage.

[Rolanbek]

The MEOS route normally converts fractional amounts of alcohol in comparison to the ALDH biochemical route.

MEOS is only relevent where the ALDH biochemical route has been overwhelmed by alcohol abuse, or is not present (in the case of our flushers).

If you regularly drink enough to trigger high level MEOS activity then your hangover is the least of your problems.

Self medication with tylenol can quickly lead to liver damage and is a definate no-no.

R

[Cluny the Scourge]

Just drink a full pint of water, maybe a 1.5 pts before you go to bed that night/morning, or before you pass out. I wake up feeling a little rough, but nothing that wouldn't stop me fetching my breakfast, jerking off, or anything of that nature.

[Erich von Manstein]

Going off of what Cluny said, it's all about electrolytes. Believe it or not, I found in college (and only a college student would try this) that downing a bottle of Gatorade through the aid of a beer bong eliminated hangovers the next day (provided I got 7-8 hours of sleep). Pop some B12 before you go to bed and you'll be right as rain the next morning.

Necessity is the mother of invention

[Rolanbek]

Electrolytes help with dehydration only, unfortunately nothing available will shield you from an excess of acetaldehyde rampaging through your body, causing muscle damage, and damage to multiple organs.

R

[Erich von Manstein]

Electrolytes help with dehydration only, unfortunately nothing available will shield you from an excess of acetaldehyde rampaging through your body, causing muscle damage, and damage to multiple organs.

R

You know, I was just about to head over to my local microbrewery to by a growler of lager when you said that. It just sounds so...ugly.

How does B12 help (or does it?). I know that B12 is produced by the liver and assumed that the liver stopped producing the vitamin while it was taking care of the massive quantities of alcohol I tend to put into it, but haven't taken a chemistry class is 6 years.

[Rolanbek]

takiing vitamin supplements appears to increase the chances of premature death according to recent study.

So no help there.

Alcohol inhibits most liver functions, so it might make some sense to stave off the inevitable alcohol induced malnutrition by taking some supplements. But then if you were drinking enough for that to be very helpful then you would be staring down to barrel of alchoholism anyway.

stick with rehydration sachets, or where you are gatorade and a packet chips, where i am lucozade and a packet of crisps.

Don't let me keep you from your pint, i'm drinking mine.....

R

[The Fish]

Hangovers are associated with a combination of dehydration (the headache is due to contraction of the meningeal layers of the brain due to loss of turgor) and hypoglycemia. Drinking plenty of water and eating something with sugar before going to sleep will usually stave off the symptoms (and it's probably the reason why people see a positive effect with Gatorade).

B12 is not produced in the liver, but is exclusively made by intestinal microorganisms. It does, however, tend to aggregate in certain organs, among them the liver and kidneys. B12 deficiency is very rare, however, and is associated with alcoholism (alcoholics tend to have global B-vitamin deficiencies due to general poor dietary habits, not due to deranged liver function). Taking B12 supplements probably doesn't do anything to stave off the ill effects of alcohol; it's main function is in proper DNA precursor synthesis (working along with folic acid).

[Rolanbek]

B12 is stored in the Liver and is released in excess into blood serum on liver damage. Alcoholics can show high serum levels of B12 and symptoms of B12 deficiency due to depletion of B12 in the liver. Self diagnoses is on the increase nowadays leading some to self treatment with B12 supplements.

These would have no theraputic effect

I must stress that the article was not really to do with hangovers per se but with incipient Acetaldehyde poisoning.

R

[Ummon]

True, but not really relevent to my comment regarding this:

Which is a false statement.

Not really. To convert acetaldehyde with high ethanol concentrations, the enzyme (which produces the excess of acetate thus stopping its own reaction) should have different kynetic properties from the existing ones.

ALDH's are natural and Acetic acid is largely a non-toxic by-product.

R

http://www.inchem.org/documents/hsg/hsg/hsg90_e.htm

2.8 Effects on Humans

In limited studies on human volunteers, acetaldehyde was mildly
irritating to the eyes and upper respiratory tract following acute
exposure for very short periods to concentrations exceeding
approximately 90 mg/m3 and 240 mg/m3, respectively.

Cutaneous erythema was also observed in patch testing with
acetaldehyde, in twelve subjects of "oriental ancestry".

One limited investigation has been reported in which the incidence
of cancer was examined in workers exposed to acetaldehyde and other
compounds.

On the basis of indirect evidence, acetaldehyde has been implicated
as the putatively toxic metabolite in the induction of
alcohol-associated liver damage, facial flushing, and developmental
effects.

Reaction is:

Ethanol --(ADH, MEOS)--> Acetaldehyde --(ALDH)--> Acetate

By accumulating, acetic acid causes consequential accumulation of acetaldehyde, whenever there's still ethanol to convert, because the first enzyme of the chain (MEOS, alcohol dehydrogenase) has higher affinity for its substrate, thus keeps producing acetaldehyde even when its conversion to acetate has ended already. The aldehyde is toxic.

You want to avoid hangover?

Butter is the solution. Fats in general interfere with ethanol absorption, thus slowing the cell intake, which in turn slows the acetaldehyde production, thefore allowing for acetate removal, and the reaction to go on smoothly up to complete detoxification.

[Rolanbek]

how is a putative imaginary enzyme with a different activation potential relevent to your false statement that there are no natural enzymes that break down acetaldehyde in the body?

So are you trying to refute me by stating acetaldehyde is toxic, which i have stated repeatedly, or did you decide that a statment regarding the toxicity of acetaldehyde was in some way relevent to a comment regarding the toxicity acetic acid? Acetic acid is non toxic, it effect on the ALDH2 and ALDH3 is well known, but to try and imply that it is toxic because it inhibits a reaction is incorrect.

R