Alcohol and Ketosis
Alcohol is one of the oldest and most widely consumed recreational psychoactive substances, and as we’ve argued previously, alcohol is clearly a part of an ancestral-type diet. By potentiating the effects of the gamma-aminobutyric (GABA) neurotransmitter and the binding to its receptor (GABA-A), it induces feelings of relaxation, euphoria, and decreases anxiety, among other cognitive functions. It also has a large role in many societies and cultures where it is legal to sell and consume it. However, the question remains, what effect does alcohol have on ketosis and the generation of ketone bodies?
We can try to break down this question by first looking at the nutritional composition of alcohol, also known as ethyl alcohol or ethanol. Ethanol in its purest form provides about seven calories per gram, however, almost no one consumes or sells pure ethanol, meaning we have to look at commonly consumed beverages. Most alcohol beverages contain far more calories per gram than pure ethanol because these drinks often contain some amount of ethanol along with other ingredients, such as sugar. Alcoholic beverages such as beer and wine can contain up to 130-200 calories per serving, 12 and 5 fluid ounces, respectively. Thus, alcoholic beverages are often considered empty sources of calories because they provide energy without any nutrients. So drinking too much alcohol can result in energy excess, especially with frequent consumption, eventually leading to weight gain. However, unless there are relatively high amounts of carbohydrates within the alcoholic drink, and added sugars, ethanol by itself does not interfere with the state of ketosis.
We can now look at how the body metabolizes ethanol. Once an individual ingests alcohol, it is absorbed by the villi within the upper region of the small intestine (and the rate at which it is absorbed can be impacted by whether an individual has eaten before drinking and the composition of the meal that was eaten before) and rapidly diffuses across various tissues within the body. Thus, the highest concentrations of alcohol will be in areas with the greatest blood flow and supply (i.e. the liver, kidneys, etc.). A portion of the amount that was consumed will easily pass through the blood brain barrier, reach the brain, and bind to the GABA receptors as mentioned above. This is also what disrupts motor function at higher doses, since alcohol is a central nervous system depressant. This becomes especially dangerous when consumed in large doses, which can even interfere with basic respiratory functions such as breathing.
The rest of the amount that was consumed will be metabolized by the liver and processed by the enzyme, ethanol dehydrogenase. This oxidative pathway is also typically referred to as the cytosolic alcohol dehydrogenase pathway because it occurs within the cytosol/cytoplasm of liver cells, and it is the principal pathway by which ethanol is metabolized within the body. The resulting aldehydes such as acetaldehyde are further processed by enzymes within the liver cells to produce acetic acid (also known as acetate), some of which eventually form water and carbon dioxide, while the rest will be converted into acetyl coenzyme A (acetyl CoA) in the hepatic mitochondria and then form acetoacetate and beta-hydroxybutyrate, both of which are ketones. These ketones are then typically converted back into their precursors (acetyl CoA) in order to generate ATP via the electron transport chain by the tissues that absorbed them. This process is depicted in the figure below from a study on alcoholic ketoacidosis:
Now, this is also where the relationship between alcohol and ketosis becomes complex. Although ethanol consumption can help produce ketones by now creating a surplus of acetyl CoA within the hepatic mitochondria, which is vital to the production of ketones when it is being metabolized, it also interferes with the production of glucose from fatty acids, and amino acids that takes place within the liver (gluconeogenesis), which can result in acute hypoglycemia. Furthermore, excessive consumption of alcohol actually promotes ketoacidosis (alcoholic ketoacidosis), by rapidly producing ketone bodies and increasing their concentration within the blood to dangerously high levels (with plasma levels reported to be as high as 15 mM), and also reducing the pH of the blood to a much more acidic state.
The issue with producing such high levels of ketone bodies is that they are generated at a much quicker rate than the rate at which they could be adequately dealt with by tissues for ATP production by converting the ketone bodies back to acetyl CoA or for elimination by the renal system. While producing ketones within the body is a goal of the ketogenic diet, high consumption of alcohol is problematic as it can have highly detrimental effects, whilst also being toxic to liver cells, and having detrimental effects on motor function.
In conclusion, even though alcohol will not interfere with ketosis or ketogenesis, consumption can actually promote the production of ketone bodies at a rapid rate, which may be especially undesirable when an individual consumes high amounts of alcohol and already has a certain level of ketones within their blood due to being on the ketogenic diet.
Thus, some caution is warranted when deciding what to drink and how much of it to drink, which we discuss in the following article.