Understanding The Hangover

17th December 2017

What is it?

Evidence found in the neolithic village of Jiahu in the Henan province of northern China suggests alcohol was discovered as a drink about 9,000 years ago.   The first hangovers can be assumed to have been discovered early the next morning.

For as long as we have been enjoying crepuscular libations we have been paying the consequences - for all the giddy joy alcohol brings, with it we inevitably have to repay that debt to our body the next day.

Alcohol works in a number of ways; mimicking the major inhibitory neurotransmitter gamma-aminobutyric acid (GABA) cells and inhibiting the major excitatory neurotransmitter, glutamate, reducing our inhibitions, responses and reactions.  Which is a pretty fine feeling after a long day at work of if you are in the mood to celebrate.  Add to this the release of the inhibitors dopamine and serotonin in the reward centre of the brain which make us feel pretty good about ourselves, and that's a recipe for a good time.

But wait.   While your inhibitions are fading, you’re becoming more relaxed and everything seems quite jolly, dark forces are at work.
 

Symptoms

Alcohol is a poison.  So if you and your friend have shared a 70cl bottle of 43% vodka, with which to set the world to rights you have effectively taken 150mls (or 6 shots) each of neat alcohol, washed down with a 200ml glass of water.  And for all the joyous feelings of inebriation that alcohol brings on, it brings with it a load of physiological consequences:

Alcohol causes the pituitary gland in the brain to block the creation of vasopressin which regulates the body's retention of water, without it the kidneys send water directly to the bladder instead of reabsorbing it into the body. 

The consumption of 64ml of alcohol in 250 ml of water (i.e. a couple of G&Ts) causes the elimination of 600 to 1,000 ml of water over several hours (1).

This is why whether you are drinking pints or shots, once you have cracked the seal on a night out you will find yourself visiting the smallest room more frequently than normal.

So now you are becoming dehydrated and your electrolytes are imbalanced.  But don’t worry, the lovely effects of serotonin and dopamine are masking the symptoms for the moment.

What you will soon begin to notice though is the nausea.  Alcohol directly irritates the stomach and intestines, causing gastritis (inflammation of the stomach lining) and increases the production of gastric acid as well as pancreatic and intestinal secretions.  Any or all of these factors can result in upper abdominal pain, nausea, and vomiting (2).

Eventually, you hit the wall; alcohol is also going to increase insulin production unnecessarily, removing usable glucose from the blood stream and storing it in the liver.   Even though alcohol is laden with sugar, come the morning your blood sugar levels are going to be pretty low.  Because glucose is the primary energy source of the brain, hypoglycemia is going to contribute to fatigue and weakness.

By now, it is probably time for a nice sleep, unless of course, you have already passed out.

Which is good.  Because now you have stopped drinking your body can get to work on the alcohol.

Most alcohol contains ethanol and methanol.  When alcohol is consumed alcohol dehydrogenase (ADH) metabolizes ethanol to an intermediate product, acetaldehyde.

Acetaldehyde causes toxic effects, such as a rapid pulse, sweating, skin flushing, nausea, and vomiting although this metabolic process generally occurs quickly and effectively but long enough to leave an effect.  Although free acetaldehyde is not present in the blood after blood alcohol levels reach zero, the toxic effects of acetaldehyde produced during alcohol metabolism may persist into the hangover period.

A second enzyme, aldehyde dehydrogenase (ALDH) metabolizes acetaldehyde to ethanoic acid, what most people call vinegar.  

ADH and ALDH also metabolize methanol; however, the products of methanol metabolism - formaldehyde and formic acid (the same acid found in ant and nettle sting) - are no fun at all, with a potential in high concentrations to cause blindness and death. 

Congeners
Certain drinks, typically darker drinks such as whisky, brandy and red wine contain more methanol – known as ‘congeners’.  Research has shown that clear spirits composed of more ethanol, such as gin or vodka, induce fewer hangover effects than darker drinks containing a large number of congeners, (3, 4).    

ALDH prefers to work on ethanol, however, so it only moves onto methanol when all of the ethanol is gone, so as long as you are drinking the ALDH doesn’t get chance to metabolize methanol.  This is one reason why the hangover kicks in once you stop.  So, is ‘hair of the dog’ a treatment to hangover?   Nope, methanol hangs around long after the ethanol has gone (5) so you have simply reset the metabolic process and delayed the inevitable.   And there are also a load of other metabolic processes going on that another dose of ethanol won’t fix.

Although a sedative, alcohol is also going to ruin your sleep as well.  Alcohol induced sleep may be shorter because of the late night and poorer quality because of “rebound excitation”.

As alcohol leaves, the body decreases sensitivity of GABA receptors and increases sensitivity of glutamate receptors in an effort to counterbalance alcohol’s sedative effects, however, the central nervous system and the sympathetic nervous system (the portion of the nervous system that coordinates response to stress) remain in an unbalanced state causing tremors, sweating, and tachycardia (5)  Your central nervous system is fighting with itself whether to get excited or chill out.

So after a bad night's sleep and your circadian (day/night) rhythm out of whack you can expect an abnormally low body temperature while you’re drunk and abnormally high in the morning.

Come the morning, sleep deprived and dehydrated with a system which has been flushed through with vinegar and rinsed in nettle sting, it is no wonder you are feeling a bit ropey.

Treatment

It is safe to say if there was a definitive treatment for a hangover after 9,000 years of experimentation we would probably all be using it by now.   Or dead through alcoholism.   Let’s look at the symptoms and what we can do about each.

Headache

Your brain is deprived of glucose and swimming in a bath of nettle sting and, as a bonus, vasodilation has caused increased intercranial pressure (accounting for the ‘throbbing’ or 'pulsating’ headache).  You will need pain relief.  

Avoid paracetamol.   You’re liver has already had a good kicking and paracetamol doesn’t like your liver anyway. 

A non-steroidal anti-inflammatory (NSAID) such as ibruprofen will reduce the inflammation but at the expense of irritating your already tender stomach lining so make sure you eat something first.  Anything.  Dry toast is a safe bet.

Gastric irritation and nausea

Antiemetic drugs are used to reduce nausea but are usually prescription-only.  Doctors tend not to have much sympathy for hangovers.   An A&E nurse will probably stab you in the face if you come to their department with a hangover.

Take ranitidine to reduce the production of stomach acids.

Dehydration and electrolyte imbalance

You will need to take on fluids.  Water will rehydrate you to a degree but not deal with the electrolyte imbalance – consider an isotonic sports drink or an oral rehydration solution such as Dioralyte.

Weakness

Your body is desperately fatigued and craving glucose.   Get some food inside you, something that is high in sugar but not too rich to upset your stomach.  It is a matter of personal choice whether you reach for a fry-up, left-over kebab or bacon flavour Wheat Crunchies.

Fatigue.

A strong black coffee is many people’s default setting for the morning after.   Caffeine will give the illusion of recovery but at the expense of increasing blood pressure, exacerbating the headache.  Caffeine is also a diuretic, furthering dehydration so all in all it is probably best to avoid caffeine until other symptoms have passed.

While drugs help they can't fix everything.  Sleep is fundamental in the recovery process.   If sleep is not an option, the only alternative is to suck it up, buttercup.   

References

1. Montastruc P. (1986) “L’alcool exagere la soif”. (Alcohol exaggerates thirst). Haut Comité d'étude et d'information sur l'alcoolisme Informations. 4:41–42.

2. Lieber C.S. (1995) “Medical disorders of alcoholism”. New England Journal of Medicine 333:1058–1065.

3. Chapman LF. (1970). “Experimental induction of hangover”. Quarterly Journal of Studies on Alcohol (Suppl. 5):67–86, 1970.

4. Pawan GL. (1973) “Alcoholic drinks and hangover effects”. Proceedings of the Nutrition Society. 32(1):15A.

5. Jones AW. (1987) “Elimination half-life of methanol during hangover”. Pharmacology & Toxicology. 60(3):217–220.