This is an article from a magazine Science in Africa: Alcohol and the inevitable hangover from over-consumption It's the end of the year and for many that means end of year staff parties, Christmas dinner and New Year's Eve, and the inevitable champagne, wine or beer. A friend always blames her hangovers on her hosts: "Honey, I was over-served last night." We have been searching for the ultimate hangover remedy for centuries, but apart from TIME itself, the ultimate hangover cure remains elusive, much to our friend's dismay. On the bright side, scientists have discovered how the body deals with alcohol, why it relaxes you, elates you, depresses you. As they say, what goes up must come down. The higher you go up, the harder you fall down. In this article we will first tell you how you go up, why you come down, and hopefully provide some assistance in choosing a strategy to break the fall. The body breaks alcohol down in several ways but the liver is the major organ tasked with its metabolism. An enzyme known as alcohol dehydrogenase breaks the alcohol down to a rather toxic compound known as acetaldehyde. It is the acetaldehyde which makes one feel ill. To complicate matters, there are five different types of these alcohol dehydrogenase genes. It is believed that a person's ability to oxidize alcohol depends on genetic make-up. People with certain types of these alcohol dehydrogenase genes, type 2 and type 3, convert alcohol much more rapidly to acetaldehyde. These genes are very common in Asian people, and the very fast build-up of the toxic acetaldehyde makes them feel very ill very quickly. Carriers of this gene are naturally discouraged from consuming much alcohol. The second step in the breakdown of alcohol is the conversion of the acetaldehyde to simple acetic acid. The liver completely metabolizes over 90% of the alcohol ingested, while the rest is excreted as sweat, urine or exhaled. The liver is a highly efficient organ at metabolizing alcohol, but good genes or bad genes, it simply cannot cope with excess amounts of alcohol or alcohol consumed too quickly, and with build ups in the toxic compound acetaldehyde as your liver struggles to cope, it is clear to see why alcohol can become toxic to you. Now take a leap from the liver to the brain. Alcohol is a central nervous system depressant. This seems at odds with the increased activity and talkativeness experienced after one or two glasses. The answer is that alcohol can cause disinhibition, that is, it inhibits cells and circuits in the brain which themselves are normally inhibitory. The brain is a multifaceted organ, consisting of different regions which perform different functions. It consists of a highly specialized network of billions of nerve cells, called neurons, which pass information rapidly as electrical or chemical signals. Neurons "talk" to each other via a range of different neurotransmitters. The neurotransmitters relevant to alcohol are dopamine, serotonin, GABA and glutamate. The major inhibitory enzyme in the brain is the neurotransmitter GABA. When alcohol binds to GABA receptors on neurons, it acts to facilitate the action of the neurotransmitter. In this case, the alcohol results in a further inhibitory effect on the brain. This may explain why it is exactly that alcohol relaxes, and yes, can lead to sedation. There are GABA receptors in many different parts of the brain, meaning that alcohol can have this effect on regions controlling memory, movement and reasoning. Furthermore, glutamate is the major excitatory NT in the brain. Ethyl alcohol acts to inhibit a subset (N- methyl-D-aspartate, NMDA) of glutamate receptors, thus diminishing the excitatory actions of glutamate. Dopamine is believed to be involved in what is known as the brain's reward system. An area of the brain known as the nucleus accumbens releases dopamine when stimulated by products such as alcohol, nicotine, drugs such as cocaine and evidence suggests, even marijuana. The release of dopamine brings about the "pleasure" response. The message is sent to the cortex where it is coded as experiences and memories. So if the release of dopamine makes one feel good, then it is natural to associate drinking with a pleasurable feeling. Serotonin, the hormone associated with mood is also linked to the reward system. What about the kidneys? The kidneys regulate fluids and electrolytes in the body - water, sodium, calcium, potassium and phosphate. Fluids and electrolytes facilitate the supply of nutrients to cells, providing stable working conditions and the clearing away of cellular waste. Alcohol's effect on electrolyte balance has major implications for the satisfactory functioning of the cells of the body. As a prime example, the cells of the brain and particularly neurons are highly dependent upon proper amounts of sodium, potassium, chloride, and calcium being available. Disruption in the proper flow and availability of these electrolytes alters the ability of the neurons to function which leads to modifications in behavior and the ability of the brain to regulate other bodily processes. Now down to the hangover. What exactly causes it? The jury is still out on this one, but common belief is that it is caused by at least 3 factors. Number one is the build up of toxins such as acetaldehyde and free radicals, as your liver struggles to cope with metabolizing large amounts of alcohol. The second culprit is dehydration. The body uses up large amounts of water to break down alcohol, so, while you drink, you become dehydrated. Water from cells across your body, including your brain is drawn upon, which may explain the sore head. The third reason is the lack of sleep. Even though you may sleep through the night, the alcohol drugs your brain so that it is unable to control tasks such as sleep. Alcohol prevents you from entering the important part of sleep, REM (Rapid Eye Movement), meaning that you do not feel well rested the following day. Now - how to deal with the side effects of alcohol consumption. If one looks at the pathway that alcohol passes through the body, it goes from the mouth into the stomach, from there into the blood stream, from there into the liver. Anything that makes it past the liver goes out into the body and gets diluted into the rest of you, including your brain, eyes, nerves etc. If a stomach is empty, it will absorb alcohol fast, hence the rule that drinking on an empty stomach is not wise. The next organ, the liver is an expensive part of the human body, which has a great many functions. The body cannot afford to have many of the enzymes needed to metabolise alcohol readily available if no alcohol is present in your body, so as a result it only keeps a small quantity of these enzymes. Hence, if one comes home and downs a bottle of wine instantly, the liver will be caught completely unprepared and will suffer, as will you. Moderation is the key. Back to the liver: the liver is run and managed by highly effective cellular business principles - if a new operation such as converting alcohol to less toxic breakdown products is called for, the raw materials to make the enzymic tools for the job are required. Enzymes in general consist of proteins with active regions that perform chemical modifications to other chemicals. These active regions often require the presence of a metal ion such as calcium, zinc or iron. They also often require the presence of things called co-enzymes, which assist the enzymes. These include things like thiamine pyrophosphate, pyridoxal phosphate and nicotinamide adenine dinucleotide. The enzymes in the liver are frequently attached to membranes which are composed of among other things various types of fatty substances. The cells in the liver are also enclosed by membranes composed of similar substances. Hence, if we are to effectively deal with alcohol, we need to be healthy, have a primed liver, have a ready supply of amino acids, coenzymes and essential fatty acids and also take a supplement of common sense with regards to what a body can and cannot do. A number of commercially available products can provide some or all of these coenzymes and essential fatty acids required for a healthier liver. A big steak, calamari, or tofu could provide the amino acids and experience could provide the understanding of when to stop. The only real answer to preventing the side-effects of alcohol consumption, is total abstinence. If consuming alcohol is unavoidable then the following popular advice may be useful: drink water to replace lost fluid, eat food before and during drinking, avoid coffee as it is a diuretic, avoid darker coloured liquors (such as bourbon) which will give you a worse hangover than lighter liquors, avoid carbonated (or bubbly) drinks like sparkling wines as these speed up the absorption of alcohol, avoid sweet drinks as these disguise the taste of alcohol fooling you into drinking more, avoid cheap liquors as these tend not to have been as extensively distilled as the more expensive brands. The search for hangover cures has brought up some very interesting and bizarre 'remedies' over the centuries. In the middle ages, for example, hangover sufferers tried to relieve their pain by eating a mixture that included raw eel. Here are some remedies from across the world which may be seriously lacking in scientific value, but the thought of which may make you swear off alcohol completely! Germany - Downing a sour herring with a beer chaser; Haiti - Stick 13 black-headed pins in the cork of the bottle that gave you the hangover; Norway - A heavy glass of cream; Outer Mongolia - Eat a pickled sheep's eye in a glass of tomato juice; Puerto Rico - Rub a lemon under your drinking arm; Russia - Heavily salted cucumber juice or black bread soaked in water! If you haven't yet decided that the trouble to your liver and brain is reason enough not to drink, and you will be consuming alcohol, do so sensibly and never drink and drive. http://www.scienceinafrica.co.za/2001/december/drinks.htm I think they should've listed neurochemistry imbalance as a forth reason for hangover(excess glutaminergic activity due to GABAergic downregulation).