The Science of a Hangover


Nothing can ruin the memories of an enjoyable Saturday night quite like the Sunday morning hangover. It greets you with a pounding headache, dry mouth, sensitivity to light, nausea, dizziness, fatigue, anxiety, and any number of additional symptoms. Beginning several hours after your last drink, when blood alcohol concentration (BAC) is falling, the hangover peaks when BAC reaches zero, which is inconveniently usually right around the time you wake up. Although the range of hangover symptoms that we all experience is vast, and depends on countless factors, such as age, weight, tolerance, number of drinks had, food eaten beforehand, hydration level, and so on, we all experience mostly the same unpleasant physical and mental symptoms that occur after a bout of heavy alcohol drinking.


On its surface, a hangover, or veisalgia as it’s technically called, seems simple; the subject drinks too much of a slightly toxic substance, which produces a pleasurable intoxicating and euphoric feeling, and then wakes up the next morning to face the consequences. But the second a drop of alcohol enters the body, a complicated, multi-step, lengthy process begins that often continues, depending on how much you drink, for well over 24 hours. Alcohol metabolism involves the interaction of the gastrointestinal, gastroesophageal, nervous, and endocrine systems, and all are involved in the customary morning-after hangover. Knowledge of the complicated causes of a hangover can move us towards the direction of figuring out a cure, once and for all.


Dehydration


The dehydrating effect of alcohol is well known and is likely the single greatest contributor to a bad hangover. However, the extent to which alcohol is a diuretic is vastly underestimated. To put things into perspective: for every alcoholic beverage you drink, you expel about 250mL of water stored in your body. There’s also an important distinction here: that liter of water does not include the liquid that the alcohol comes with. So, for instance, if you have four 12oz beers (a 12oz beer is 350mL), your body will expel 1L of water stored in your body plus the 1.4L of beer after it passes through your digestive system. This water expulsion literally shrinks your brain, and as the outer membranes of the brain pull on the skull, headaches ensue (1).

The reason alcohol has such a significant dehydrating effect is because of its effect on the pituitary gland. The pituitary gland is a hormone-secreting pea-sized organ at the base of your brain known as the body’s “master gland,” as it plays a major role in regulating body functions and controlling the activity of most other hormone-secreting glands. One of the hormones it controls is vasopressin, which is a hormone that manages the balance of fluids and electrolytes in the body. Alcohol, by inhibiting electrical currents that signal your pituitary gland to release vasopressin (2), prevents the body from properly controlling the balance of liquids, and it leads to the expulsion of large amounts of water through urination. On top of this, vasopressin plays an important role in encouraging the kidneys to reabsorb water and electrolytes that are on their way to becoming urine. As much as 67% of liquid that passes through your kidney is reabsorbed into your body right before urine is produced. However, with decreased levels of vasopressin, that reabsorption process is severely hindered, leading to increased urination and dehydration.


Gastrointestinal System


The acid in your stomach that breaks down food is, simply put, extremely acidic. On the pH scale, gastric acid registers at the very bottom, somewhere between 1 and 2. For any Breaking Bad enthusiasts, you may remember that chilling scene when the acid Jesse uses burns a hole through his bathtub and floor. That acid is hydrofluoric acid and has a pH of 3.27. Since pH uses a logarithmic scale, this means that your stomach acid is over 10 times as acidic. While this is not a perfect comparison because acidity does not exactly correlate with corrosiveness, it serves to illustrate an important point: the acid in your stomach is very, very strong. When large amounts of alcohol are consumed, gastric acid production increases sharply to cope with the influx, and the presence of extra acid irritates your stomach and intestines and can cause widespread inflammation that causes the common nausea and vomiting symptoms🤢. Furthermore, when considering the gastrointestinal system, alcohol is a double-edged sword. While it increases the production of gastric acid, it also slows gastric motility, which is the physical emptying of the stomach. With slower gastric motility, all that gastric acid stays in the stomach for longer, increasing the likelihood and severity of the aforementioned symptoms. A study from 2016 noted that beverages with an alcohol content greater than 15% are the real culprits when it comes to inhibiting gastric motility, so there’s part of the reason you might start to feel sick after a few rounds of shots (3).


Metabolism


Now, with an understanding of the physiological processes that take place upon consumption of alcohol, we can turn our attention to the substance itself. Alcohol is made primarily from ethanol, a flammable, colorless, and slightly toxic chemical compound. Upon ingestion, the liver metabolizes the alcohol using a cascade of enzymes: first, alcohol dehydrogenase, and then aldehyde dehydrogenase. The end product is a relatively harmless compound. However, the intermediate product of this reaction (what alcohol dehydrogenase produces), is highly toxic—much more toxic than alcohol itself. So, if we are ingesting high volumes of alcohol, this metabolic process gets “clogged up,” and we produce too much of the intermediate product acetaldehyde. Although we have natural mechanisms for neutralizing this product, it’s the same story: too much of it, and the body can’t deal with it all. The result is that blood circulates this toxin around the body, and leads to rapid pulse, sweating, skin flushing, nausea, and vomiting. Acetaldehyde is not the only toxin that circulates in the body during drinking. Lactic acid production increases drastically and inhibits glucose production. While we may associate glucose with candy and fruit, it is the primary energy source of the brain, and as we exhaust our supply, the brain literally starts to run out of energy (4). Low blood sugar, or hypoglycemia, contributes to hangover symptoms like fatigue, weakness, and general poor mood.


Sleep

Possibly the most misunderstood component of drinking alcohol is sleep. While alcohol has sedative effects that can promote sleep onset, the fatigue is not a product of our natural circadian rhythm kicking in, but rather a product of an artificial and temporary suppression of many of the neurological pathways that keep us awake. Once asleep, that same suppression prevents us from entering REM sleep, a vital phase of sleeping that helps us rest and recover (5).

Unfortunately, this unrestful sleep doesn’t last long. After blood alcohol concentration falls, the body experiences a “rebound effect,” where the neurochemical processes that were being inhibited suddenly turn on again: core temperature rises, cortisol levels spike, and the major excitatory neurotransmitter in the central nervous system, glutamate, comes back online. This is the reason we often go to bed late after a night drinking, and then wake up much earlier than we would have liked—that, and the pounding headache that might be taking place. So, while the precise neurobiological mechanisms that underlie alcohol’s prevention of quality sleep are still being uncovered, what we know so far does not paint a flattering picture of the few hours of sleep we might pick up after drinking.


Congeners


So far, we have only spoken about alcohol’s main component, and the main culprit in your inebriation and subsequent hangover. However, alcohol is not pure ethanol; among common ingredients such as water, malt, potatoes, corn, rice, and others, are congeners. Congeners are minor chemical constituents of alcohol which give a distinctive character to different types, and they can be responsible for some of alcohol’s physiological effects. They are produced along with ethanol during fermentation or can be added during production. Beverages that are purer in their ethanol content, such as the clear liquors (vodka, gin), induce fewer hangover effects compared to beverages containing a large concentration of congeners, such as whiskey or red wine. One of the most common congeners is methanol, a relative of ethanol. The same enzymes (alcohol dehydrogenase and aldehyde dehydrogenase) that metabolize ethanol also metabolize methanol, but the products of methanol metabolism are formaldehyde and formic acid, which are extremely toxic to the body.


On the topic of other types of alcohol, as a side note, there is another type of alcohol called isopropyl alcohol which readers may recognize from their hand sanitizer and rubbing alcohol bottles. This type of alcohol, great for keeping us safe from COVID-19, is as adept at hurting us if swallowed as it is at killing germs—the body metabolizes the substance into acetone, a highly toxic compound that you may recognize as nail polish remover and has a mortality rate of almost 50% if overdosed on.


In Summary...


This article is not meant to dissuade you from drinking. An equally informative and scientifically sound article could be written about the physiological and psychological benefits of consuming alcohol and socializing, and it would be a fairly safe assumption to think that most readers look forward to drinking a couple times a week. However, knowledge of the internal processes that take place upon alcohol consumption allows us to better prepare ourselves for a night out and instructions for how to deal with it the next morning.

Although there are no “magical” hangover cures, next week’s article will give you a plan for knocking out most hangovers before they even start.


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