As another December comes around, the season to be jolly is well and truly here. For many of us, our diaries are filling up with office parties, family reunions, and overdue catch-ups with friends — our bellies are also filling up with mulled wine and eggnog.

This means, of course, that it is also time to reacquaint ourselves with that old party pooper: the hangover. It’s somewhat surprising, considering the amount of magazine space given to the problem every December and the array of “cures” on the shelves of your local pharmacy, that the scientific community still can’t pinpoint exactly which component of your tipple is to blame. (Even though they have given the condition a nicer name than “hangover”: veisalgia .)

Why do some of us wake up in ruins the morning after, even when we stick to “pure” craft beers brewed in the mountains by monks, and fermented using virgins’ tears? How come John from accounts, who practically took up residence in the punchbowl, can bound into the office at 8 a.m. the next day, full of festive cheer? Also, is there a reason why we can shrug off a hangover with our morning coffee in our late teens, but it becomes a week-long event in our 40s?

The most common explanation for the hangover is that alcohol (or ethanol, its purest form) acts as a diuretic, thus increasing urine production. Most people neglect to drink water during (or even after) a party and, as a result, they end up with a mouth like the Mojave Desert and bodies that lack the required hydration to function normally.

But studies examining the link between dehydration and hangovers tell a somewhat different story. For example, there is apparently no correlation between high levels of the hormone vasopressin, which is associated with dehydration, and the severity of a hangover. So while most experts agree that dehydration accounts for the dizziness and the thirst, there are probably other factors at play.

What happens to the body when drinking?

To understand other theories, it is probably best to outline what happens to alcohol in the body. Firstly, it is broken down into a chemical called acetaldehyde by an enzyme called alcohol dehydrogenase (ADH). Acetaldehyde is then broken down further by acetaldehyde dehydrogenase (ALDH). Both of these enzymes, however, require a coenzyme (or associated molecule) called NAD+, which gets used up in the process.

The problem is that NAD+ is needed for a range of reactions in the body, from absorbing glucose from the blood to regulating electrolyte levels. So, NAD+ depletion would logically lead to hangover-like symptoms. This was a generally accepted theory for a number of years, and still is in some quarters. However, Professor Joris C. Verster, from the University of Utrecht in the Netherlands, has skewered this idea. He pointed out that people suffering from severe hangovers were not found to have lower levels of electrolytes or blood glucose.

Most modern theories seem to point the blame not at alcohol per se but instead at acetaldehyde, given that it is thought to be up to 30 times more toxic than alcohol itself. In controlled studies using mice, it’s been found to cause symptoms such as sweating, skin flushing, nausea, and vomiting, all of which might sound familiar. Interestingly, numerous research papers stretching back over the past decade and beyond note that one’s own immune system could be a large part of the problem.

It is now well demonstrated that the hangover is accompanied by significant increases in the body’s “signaling chemicals,” or cytokines. An increase in cytokine production can signal a fever or an inflammatory response to battle an infection (such as a viral infection). The symptoms we experience during a fever are not a direct effect of the invading organism, but are a result of our body’s attempt to deal with it.

Muscle ache, fatigue, headache or nausea, as well as cognitive effects, like memory loss or irritation, are appropriate responses for our body when dealing with a pesky microbe invasion, but may simply be the wrong response to too much alcohol.

Why some people can handle alcohol?

Going back to John from accounts, it’s probable his genetics have helped him out to start, according to Sally Adams, a lecturer in health psychology at the University of Bath. Her research into hangovers compared those among identical twins to those of non-identical twins.

Because identical twins share all of their genes and non-identical twins share only about 50 percent of their genes, any differences observed in variation of identical twins’ hangover experience can only be the result of the environment rather than genes. However, we still cannot isolate exactly what genes are involved, although they are not likely the same ones that cause the so-called “Asian glow.”

There is a common myth that many Asian people cannot handle alcohol because they lack sufficient alcohol dehydrogenase. In truth, the problem stems from the fact that they process alcohol a bit too quickly. Around 80 percent of Asian people (less common in Thailand and India) have a variant of the gene coding for the enzyme alcohol dehydrogenase called ADH1B, whereas almost all Japanese, Chinese, and Korean people have a variant of the gene called ADH1C, both resulting in an alcohol dehydrogenase enzyme that converts alcohol to toxic acetaldehyde at a much higher efficiency than other gene variants from Caucasians.

But the story does not end there. In about half of all Asian people, the increased acetaldehyde accumulation is worsened by another gene variant. This results in a less functional acetaldehyde dehydrogenase, an enzyme that’s charged with the breakdown of acetaldehyde. The net result is that affected people may be better at metabolizing alcohol, but show far more acetaldehyde-based side effects while drinking.

A number of other factors are thought to affect one’s ability to metabolize alcohol. For instance, studies have shown that women tend to report worse hangovers. This is likely because they generally have less body mass (they’re lighter). In addition, studies have suggested that people in their early 20s tend to suffer less after alcohol consumption than older people, but there is conflicting evidence about this. Research on the subject tends to be based on surveys, and it’s highly probable that older people, while drinking the same quantities, may do so over the course of a longer evening — and perhaps at a slower pace.

Why do some drinks cause worse hangovers?

Congeners, also known as fusil oils, are a byproduct of the fermentation process. They are, essentially, impurities of which there can be hundreds of different types, including the already mentioned acetaldehyde and methanol (which is quite nasty). In effect, our bodies treat them as a poison, and a headache is a very common symptom of poison processing.

Because all alcoholic beverages begin with fermentation, any type of booze is likely to have congeners but distillation may remove many of them. It is for this reason that clear spirits (such as gin or vodka) tend to produce less intense hangovers than congener-rich spirits (red wine or cognac). In March 2010, Brown University’s Center for Alcohol and Addiction Studies published research in Alcoholism: Clinical and Experimental Research demonstrating how young drinkers who received bourbon to the point of intoxication were in a sorrier state the following day than their peers who drank vodka to the same point of intoxication .

So, it is best not to equate quality beer with a breezy outcome, as craft beer is typically replete with congeners. It is these impurities, after all, which give flavor, an appetizing smell, and a pleasing appearance. Too many of these means that you will have a difficult time clearing them from your body.

The problem might not be the congeners themselves, however, but, like alcohol, how your body processes them. Methanol, the most notorious congener, is converted by alcohol dehydrogenase to formaldehyde, which is toxic. It’s not hard to imagine a whole array of chemicals might be swimming around in our body after a night on the tiles, given the different ways so many of these congeners might be processed. These reactions are likely so complex that they could explain why mixing different sorts of liquor can cause a hangover — a greater variety of congeners could lead to a wider variety of effects, as well as a greater need for painkillers.

Whatever the ultimate cause, don’t expect the scientific community to pump much money into deciphering the riddle. For that reason, many scientists feel there would be a moral hazard in trying to find a cure.  Indeed, we should really see it as a friend,  albeit one that doesn’t pull any punches.

Dr. John Carrigan is a biochemist from Dublin, Ireland with over 10 years experience in both the biotech and research environments. He has worked in such diverse fields as engineering enzymes for diagnostic kits and analyzing the metabolic effects of cancer. More recently, he has been focused on the potential for algae oil as a food source. When away from the lab he likes to write, drink Guinness, and bet on horses.