How to define ketosis?

Written by Marina Lommel
7 minutes reading time
19. April 2023

Ketosis and ketone bodies. These two terms are happily thrown around in the low carb and keto world. Can be measured somehow. But what is actually behind it? What do these things mean in metabolism and at the chemical level?

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    The official definition of ketosis is “a metabolic state in which the concentration of ketone bodies in the blood is elevated above normal.” That doesn’t say much. What is the normal value? This is the value that an Otto normal average eater has, if he is not fasting for a long time or giving up carbohydrates. Our average Joe eater probably had a cheese sandwich an hour ago and a Snickers bar just now. He eats like 3-6 times a day and he even fasts daily, namely when he sleeps.

    Such an Otto normal average eater has a ketone body concentration in the blood of less than 0.1 mmol per liter. So that’s the normal value and if you have that value in your blood, you’re not in ketosis. When a person is in ketosis, the values are usually between 2-5 mmol/L. This is absolutely physiological, i.e. a healthy state. By the way, mole and mmol are a unit of measurement for chemists, similar to kg and g for the cook.

    1. what are ketone bodies?

    Ketone bodies are small molecules that supply organs with energy.

    In medicine, three compounds are referred to as ketone bodies: Acetoacetate, β-hydroxybutyrate and acetone. Acetoacetate is a “ketocarboxylic acid,” β-hydroxybutyrate is a “carboxylic acid,” and acetone is the simplest “ketone.” Ketocarboxylic acids, carboxylic acids and ketones are different types of small organic molecules. Carbon atoms, oxygen atoms and hydrogen atoms are connected in different ways in different molecules. The important thing is: There is energy in these connections!

    2. are ketone bodies and ketones the same thing?

    Ketone bodies and ketones are not the same thing.

    Ketones is the umbrella term for all chemical compounds that have a double bond from a carbon atom to an oxygen atom, but only if it is not at the edge of the molecule. Is officially called “a non-terminal carbonyl group”. There are an incredible number of variants of such molecules, such ketones. However, there are only three ketone bodies and they get their name from the fact that acetoacetate and acetone each have such a “non-terminal carbonyl group” in their chemical structure. So: 2 ketone bodies belong to ketones, but not all ketones are ketone bodies. (Raspberry ketones can be sold as promising as they are, they have absolutely nothing to do with ketosis).

    β-Hydroxybutyrate is not chemically a ketone because the keto group has been reduced (converted) to a hydroxy group. Nevertheless, it is counted among the ketone bodies because it can be rapidly converted from acetoacetate and has comparable properties in the body. Moreover, it is the most abundant among the ketone bodies and the most important ketone body in metabolism.

    3. how are ketone bodies excreted?

    Some ketone bodies are excreted through urine and breath.

    β-Hydroxybutyrate is converted from acetoacetate by enzymes. Acetone, on the other hand, is formed by spontaneous decomposition of acetoacetate, without enzymes. It is volatile and is virtually unused in metabolism. Instead, it is released primarily through the lungs with the exhaled air. This is responsible for the sweetish mouth odor.

    Ketone bodies are also excreted in the urine. This is called ketonuria – the excretion of ketone bodies in the urine. Over time, the excretion decreases because the ketone bodies are better utilized by the organs and the body would be stupid to simply flush out these energy carriers.

    4. does the liver produce ketone bodies even without ketosis?

    Even without ketosis, the liver constantly produces ketone bodies in small amounts.

    In a normal, non-ketogenic metabolic state in healthy humans, small amounts of ketone bodies are continuously synthesized by the liver and consumed by other organs. The concentration of acetoacetone and β-hydroxybutyrate after a meal is about 0.01 mmol per liter of blood. Even after overnight fasting, their concentration in the blood is still relatively low at 0.1 mmol/L. It only increases gradually with continued abstinence from food, reaching 2 mmol/L after about three days of fasting and about 5 mmol/L after one week without food intake. In this range, it is called ketosis.

    Blood glucose levels are at the lower edge of physiological concentrations during ketosis, maintained by gluconeogenesis from amino acids and glycerol. Gluconeogenesis is the building of glucose from molecules that are not carbohydrates, such as amino acids from proteins or from glycerol a part of triglycerides, the fats.

    5. is ketosis a physiological metabolic state?

    Ketosis is a completely physiological metabolic state.

    Ketosis, a physiological (normal and healthy) state when food is abstained from, should not be confused with ketoacidosis, a pathological (diseased) state that occurs in diabetes and alcohol abuse and can become life-threatening. In uncontrolled type I diabetes, the ketone body concentration can rise to 25 mmol/L, at which point dangerous ketoacidosis develops. This overloads the buffer mechanisms of the blood that normally take care of the acid-base balance, and the blood becomes overacidified. However, when a healthy person fasts or eats a very low-carbohydrate diet, such harmful levels are not reached.

    It was the biochemist Hans Krebs (discoverer of the Krebs cycle aka citrate cycle) who first spoke of “physiological ketosis” as a distinction from diabetic ketoacidosis. Increased ketone body concentrations within a physiological framework occur, as already mentioned, not only during fasting, but also during carbohydrate-limited, so-called “ketogenic diets“.

    6. how is ketosis disturbed?

    Small amounts of insulin or glucose quickly destroy ketosis.

    The metabolic state of ketosis is very fragile and can be rapidly interrupted by the administration of insulin or glucose. Especially in the early days when the liver and other organs are just changing over and learning to produce and use ketone bodies. Carbohydrate intake leads to insulin secretion. Insulin inhibits ketone body production and causes ketone bodies to be excreted in the urine. A high amount of protein also causes insulin to be released, but does not have quite as strong an effect on ketosis. This is because protein intake is accompanied by the simultaneous release of glucagon, the antagonist of insulin.

    7. what do ketone bodies do?

    Ketone bodies transport energy through the blood.

    The small ketone bodies are energy-rich compounds. There is also a lot of energy in fat. But what happens when you mix water and fat? Does not quite work. Since our blood consists mainly of water, it is also a bad idea to try to dissolve fat in it in order to transport energy from point A to point B. Therefore, the liver first converts the fat into small ketone bodies. The emphasis here is on small, because that is one of the reasons why ketone bodies are highly soluble in water. Unlike fat, they can be easily transported with the blood. In human evolution, the capacity for ketogenesis (production of ketone bodies) and ketolysis (utilization of ketone bodies) enabled survival during long periods of starvation, since the ever-expanding brains of human ancestors could be provided with a source of energy from fat reserves.

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    Cancer HA. 1966. The Regulation of the Release of Ketone Bodies by the Liver. Adv Enzyme Reg, 4: 339-354.

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    Stipanuk MH, Caudill MA. 2013. Biochemical Physiological and Molecular Aspects of Human Nutrition. Third ed. Philadelphia: Elsevier Saunders, 379-381.

    This article was written by

    Marina Lommel

    Marina gründete Foodpunk nach ihrem Abschluss in Ernährungswissenschaften und ist aktuell CEO des Unternehmens. Während ihres Studiums arbeitete sie in verschiedenen Bereichen, darunter in der Wissenschaftsredaktion beim Radio, Redaktion beim TV und Uni-Wissensmagazin sowie im Labor am DZNE in der Parkinsonforschung. Marina ist außerdem Autorin von 5 ernährungswissenschaftlichen Sachbüchern.

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