Most of us enjoy a glass of wine or a cold beer now and then. But have you noticed how the same few drinks can leave you buzzing one night and flattened the next? Or why you crave hot chips at 3am, or wake up puffy and exhausted? Nearly all of it traces back to one thing: alcohol floods your cells with a high-energy molecule called NADH, faster than your mitochondria can deal with it. What happens next depends on what you ate, what you do for the rest of the night, and how well your mitochondria were working to begin with.
I first wrote this in 2019 as a night out told stage by stage, and I’ve kept that, because it’s the easiest way to follow what’s happening inside you. If you’d like more background on how your cells make energy, start with what mitochondrial dysfunction means for you.
The short version
- Your body burns alcohol before food, because it has nowhere to store it.
- Breaking alcohol down produces large amounts of NADH, an energy-carrying molecule. In small amounts that feels good. In large amounts it jams up energy production.
- That jam slows your main energy engine, pushes sugar towards lactate, stops your liver topping up your blood sugar overnight, and shifts your liver towards making and storing fat.¹
- Acetaldehyde, the first thing alcohol turns into, is toxic. It causes the red flushed face and contributes to how rough you feel.²
- Moving burns off some of the excess. Sitting still lets it pile up.
Why your body burns alcohol first
Food has to be digested before it can be used, which takes hours. Alcohol is absorbed quickly and goes straight to your liver. And unlike sugar or fat, your body has no way to store alcohol for later. So it has to deal with it immediately, and it puts alcohol to the front of the queue while your dinner waits.²
In your liver, alcohol is converted in two steps. First it becomes acetaldehyde, which is toxic. Then an enzyme called ALDH (aldehyde dehydrogenase) turns acetaldehyde into acetate, which is relatively harmless and can be used as fuel. Both steps hand off energy in the form of NADH.¹˒²
Stage 1: dinner and drinks
You’re out with friends, a meal in front of you, a few drinks in. All that NADH from the alcohol is fuel, and your mitochondria can feed it straight into their energy chain. You feel warm, chatty and full of energy. Life is good.
How you feel at this stage depends a lot on how quickly you clear acetaldehyde. Some people’s ALDH enzymes work quickly and they can drink a fair amount without much effect. Others go red in the face and feel unwell after one glass. That flush is acetaldehyde building up.²
Oxidative stress also slows ALDH down. This is why I so often hear “I used to enjoy a drink, but since I got sick even one glass affects me for days.” I’ve written about that in detail in why you can’t tolerate alcohol or chemical smells.
Some acetaldehyde also reaches the brain, where it can combine with dopamine to form a compound called salsolinol. In animal research it has been linked to the rewarding pull of alcohol, the urge to have another, though the evidence is still mixed.³
Stage 2: the night forks
By now your dinner is digesting and releasing sugar into your blood. But your cells already have more NADH than they can use. When that happens, your mitochondria slow down their main energy engine, the Krebs cycle, because they don’t need any more NADH from food.¹ What happens next depends on what you do.
If you sit at the bar and keep drinking, the NADH keeps piling up with nowhere to go. Sugar from your meal can’t enter the Krebs cycle, so it gets stuck at an earlier step and is turned into lactate instead.¹ A build-up of lactate is part of why heavy drinking leaves you sluggish and achy. If you get muscle aches without exercising, lactate is often part of that picture. It’s possible this shift is also protective: running less through the mitochondria means making fewer free radicals.
If you love to dance, you’re giving that excess NADH somewhere to go. Working muscles burn energy, which lets the mitochondria clear the backlog.
A personal confession here, not to brag but because it stuck with me. Years ago I was a competitive runner, at the fittest I’ve ever been and training up to three hours a day. At my now sister-in-law’s bachelorette party I had a few drinks and danced all night. At 3am, when everyone else crashed, I was wide awake. So I went for a run along the beach. It was closer to a sprint, 10 kilometres in 34 minutes, and the next day I had no hangover at all. It felt like running on ethanol fumes, and once they were burned off I felt great. I’m certainly not recommending it.
I don’t have research to prove why, but my interpretation is this: very fit people have far more mitochondria, so they have more capacity to burn off excess NADH instead of slowing everything down. Their body seems to push them to move. If you feel heavy and exhausted after only a drink or two, it may say something about how well your mitochondria are coping in general.
Stage 3: the 3am pizza craving
When there’s more sugar and NADH than your cells can burn, the excess gets stored, as glycogen and as fat. The high NADH also shifts your liver towards making fat and away from burning it.¹ Do this often enough and the fat stays in the liver. That’s how alcohol-related fatty liver starts.
The same jam has another effect. Overnight, your liver normally keeps your blood sugar steady by making fresh glucose. High NADH blocks that process.¹ So a few hours after your last drink, your blood sugar dips. That’s the shaky, irritable, starving feeling that has you hunting for hot chips and pizza at 3am, and it’s part of the next day’s mood swings.
If you keep drinking, your liver brings in a backup system for breaking down alcohol, called MEOS. It relies on an enzyme (CYP2E1) that produces a lot of free radicals and uses up NADPH, the same molecule you need to recycle glutathione, your main antioxidant.² So the more you drink, the more free radical damage you create and the less antioxidant capacity you have to deal with it.
Meanwhile, acetate can’t easily enter the stalled Krebs cycle, so some of it is turned into ketones. Together with the lactate, that makes your system more acidic.¹
The morning after
A hangover isn’t one thing. Leftover acetaldehyde, low blood sugar, a backlog of lactate, dehydration and poor-quality sleep all play a part, and people differ in which one hits them hardest. What this story explains is why some nights are so much worse than others. Eating well, drinking slowly and moving all give your cells a chance to keep up. A heavy meal, lots of drinks and sitting still all night stack everything against you.
If you burned off the excess and went to bed with enough food and fluids on board, you may well wake up feeling fine.
When drinking becomes a habit
With regular heavy drinking, the liver adapts by making more of the MEOS enzyme, so it clears alcohol faster, and creates more free radical damage as it does.² Over years, fatty liver can progress to alcoholic hepatitis and then cirrhosis. A badly damaged liver can’t clear ammonia properly, and ammonia is toxic to the brain.
The brain adapts too. Heavy drinkers’ brains take up and burn acetate from alcohol faster than light drinkers’ brains do. Burning acetate also produces adenosine, which has a calming, sedating effect. When someone stops drinking suddenly, losing both that fuel and that calming signal may be one contributor to how awful withdrawal feels.⁴
Alcohol withdrawal can be dangerous, including seizures. If you drink heavily every day and want to stop, please do it with your GP’s support rather than on your own.
This isn’t only about alcohol
Much of what I’ve described isn’t unique to alcohol. Overeating, especially lots of refined carbohydrate in one sitting, can overload the same energy pathways in a similar way. Yeast in the gut can also make acetaldehyde from sugar, which is one reason some people with yeast overgrowth describe feeling hungover without having had a drink.
Frequently asked questions
Why do I feel energetic when I start drinking and exhausted later?
Breaking down alcohol gives your cells a flood of NADH, an energy-carrying molecule, which feels good at first. Once there’s more than your mitochondria can use, they slow down energy production, and that backlog is what leaves you tired.
Why do I crave carbs late at night after drinking?
Alcohol stops your liver making fresh glucose overnight, so your blood sugar drops a few hours after your last drink. Your body responds with strong cravings for quick sugar and starch.
Why does my face go red when I drink?
Facial flushing comes from acetaldehyde, the toxic first breakdown product of alcohol, building up faster than your ALDH enzymes can clear it. It’s more common in people with slower versions of that enzyme.
Can alcohol cause fatty liver even if I’m not a heavy drinker?
Every time you drink, alcohol shifts your liver towards making fat and away from burning it. The more often and the more heavily you drink, the more that fat builds up. It’s one of several possible contributors to fatty liver, alongside diet and blood sugar regulation.
Why can’t I tolerate alcohol since I got sick?
Ongoing illness often means more oxidative stress, and oxidative stress slows down ALDH, the enzyme that clears acetaldehyde. That leaves acetaldehyde around for longer, so the same drink hits much harder.
Does exercise really help clear alcohol?
Exercise doesn’t make your liver break alcohol down faster, and you shouldn’t exercise while intoxicated. But using your muscles gives the excess NADH somewhere to go, which may ease some of the sluggishness that comes from sitting still while drinking.
References
1. Cederbaum AI. Alcohol metabolism. Clin Liver Dis. 2012;16(4):667-685. PMID 23101976.
2. Zakhari S. Overview: how is alcohol metabolized by the body? Alcohol Res Health. 2006;29(4):245-254. PMID 17718403.
3. Kurnik-Łucka M, Panula P, Bugajski A, Gil K. Salsolinol: an unintelligible and double-faced molecule — lessons learned from in vivo and in vitro experiments. Neurotox Res. 2018;33(2):485-514. PMID 29063289.
4. Jiang L, Gulanski BI, De Feyter HM, et al. Increased brain uptake and oxidation of acetate in heavy drinkers. J Clin Invest. 2013;123(4):1605-1614. doi:10.1172/JCI65153.
