Alcohol is metabolized by a family of Alcohol dehydrogenase enzymes (ADH) and Aldehyde dehydrogenase enzymes (ALDH) in the liver1. These enzymes require cofactors & coenzymes to perform their reaction. Zinc holds the alcohol in it place and Nicotinamide adenine dinucleotide (NAD) which is constructed from Nicotinamide, performs the chemical reaction. The levels of these cofactors and coenzymes deplete during alcohol consumption2. Lack of these cofactors & coenzymes leads to the inefficient metabolism of alcohol, and the build up acetaldehyde. Inefficient metabolism of alcohol is due to low activity of ADH and ALDH enzyme3. Inefficient metabolism of alcohol leads to the build up of acetaldehyde, a toxic molecule that is damaging to the body’s organs, and causes the symptoms commonly know as hangover. Factors effecting the severity and onset of acetaldehyde build up depend on genetic factors, gender, age, weight, fatty liver syndrome (hepatic steatosis) and the amount of alcohol consumed. The enzyme’s activity is solely dependent on the level of available cofactors and co-enzymes. Regardless of the enzymes level, the efficient activity of this enzyme is promoted when there are enough cofactors and coenzymes available to perform the reaction.
Alcohol is metabolized (broken down) by the body at a rate of 0.016% per hour. It doesn’t matter if you are 6’4” or 4’6,” or if you drink red wine or moonshine. Once your blood alcohol concentration (BAC) reaches a certain level, no matter how it got to that level, your body needs time to break the alcohol down and remove it from your system.
The concentration of the oxidized form of nicotinamide adenine dinucleotide (NAD+) reaches its rate-limiting state shortly after ingestion and remains constant. Ethanol elimination is approximately zeroth order, supporting the suggestion that the reaction is limited by the amount of enzyme, co-substrate, or both4(D.M. Umulis et al).
What Causes a Hangover?
There is no way to avoid or prevent a hangover, other than to avoid alcohol altogether. There are 7 major biochemical reactions to alcohol metabolism.
Alcohol, and too much of it, triggers a cascade of reactions in your body that contribute to the symptoms known as a hangover. These include:
- Increased Urination: Alcohol is a diuretic. For every 200 ml of alcohol consumed, you will produce 320ml of urine. Alcohol inhibits the secretion of vasopressin. When this enzyme is suppressed, water is sent right to your bladder (along with electrolytes) to be excreted, causing you to urinate more often.
- Dehydration: Increased urination can lead you to become quickly dehydrated, and as your body draws water from your brain to function, it may leave you feeling fatigued or dizzy.
- Acetaldehyde build-up: When alcohol reaches your liver, an enzyme called alcohol dehydrogenase breaks it down into acetaldehyde. Acetaldehyde is far more toxic than alcohol (by up to 30-fold). So your body again attempts to break it down with the enzyme acetaldehyde dehydrogenase and glutathione, a powerful antioxidant that is crucial for liver detoxification (glutathione contains high levels of cysteine, which is why taking this in supplement form may help avoid hangover symptoms). Together, this powerful detox duo can break down the acetaldehyde into harmless acetate (which is similar to vinegar). However, when you drink too much alcohol, your stores of glutathione become depleted, which allows acetaldehyde to build up in your body, causing the toxic hangover effect. It should be noted that women have less acetaldehyde dehydrogenase and glutathione than men, which is why women may have a more severe reaction to drinking the same amount of alcohol as a man of similar weight.
- Congeners: Congeners are ingredients produced as byproducts of fermentation and distillation. They include acetone, acetaldehyde, tannins, and some flavorants in different alcoholic beverages. Congeners are thought to make the effects of a hangover worse and are found in higher amounts in darker liquors (such as brandy, whiskey, and red wine) than clear liquors like vodka or gin.
- Glutamine rebound: Alcohol inhibits glutamine, a natural stimulant in your body. This is partly why alcohol has a depressive effect that may make you fall asleep easily… at first. After you’ve stopped drinking, your body will work overtime increasing glutamine levels, which is why you’ll ultimately wake up more often and have a more restless night’s sleep after you drink. This glutamine rebound may contribute to the fatigue, tremors, anxiety, restlessness, and even increased blood pressure that are often felt during a hangover.
- Disruptions to your stomach lining, blood vessels, and blood sugar: Alcohol is irritating to your stomach lining and leads to an increased production of stomach acid. This can cause nausea, vomiting, and stomach pain. Alcohol can also lead to dips in your blood sugar level, which can lead to shakiness, mood swings, fatigue, and seizures. Also, alcohol may cause your blood vessels to expand, which may trigger headaches.
- Inflammatory response: Finally, alcohol also provokes an inflammatory response in your body in which your immune system may trigger agents that provoke hangover symptoms including memory problems, decreased appetite, and trouble concentrating.
- Swift, M.D., Ph.D.; and Dena Davidson, Ph.D. Alcohol Hangover. Mechanisms and Mediators. Alcohol Health & Research World. Vol. 22, No. 1, 1998
- McElfresh KC, McDonald JF. The effect of alcohol stress on nicotinamide adenine dinucleotide (NAD+) levels in Drosophila. Biochem Genet. 1983 Apr;21(3-4):365-74
- Michael Hardman, Rachel A. Page, Mark S. Wiseman andKathryn E. Crow. REGULATION OF RATES OF ETHANOL METABOLISM AND LIVER [NAD+]/[NADH] RATIO. Department of Chemistry and Biochemistry Massey University Palmerston North NewZealand
- David M. Umulis1, Nihat M. Gu¨rmen, Prashant Singh, H. Scott Fogler A physiologically based model for ethanol and acetaldehyde metabolism in human beings. Alcohol 35 (2005) 3–12