What is the difference between ketosis and ketoacidosis

How do you define ketosis?

Ketosis and ketone bodies. These two terms are happily tossed around in the low carb and keto world. Can you measure it somehow. But what is actually behind it? What do these things mean on a metabolic and chemical level?

The official definition of ketosis is: "A metabolic state in which the concentration of the ketone bodies in the blood is higher than normal". That doesn't say much yet. What is the normal value? This is the value that the average eater has when he is not fasting for long periods of time or doing without carbohydrates. Our average eater probably had a cheese roll just an hour ago and a Snickers just now. He eats 3-6 times a day and he even fasts every day, namely when he sleeps.

The average eater like this has a ketone body concentration in the blood of less than 0.1 mmol per liter. So this is the normal value and if you have this value in your blood then you are not in ketosis. If 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, mol and mmol are a unit of measurement for chemists, similar to kg and g for cooks.

Ketone bodies are small molecules that provide organs with energy

In medicine, three compounds are called ketone bodies: acetoacetate, β-hydroxybutyrate and acetone. Acetoacetate is a “ketocarboxylic acid”, β-hydroxybutyrate is a “carboxylic acid” and acetone is the simplest “ketone”. Keto carboxylic acids, carboxylic acids, and ketones are different types of small organic molecules. Carbon atoms, oxygen atoms, and hydrogen atoms are linked in different ways in different molecules. It is important that there is energy in these connections!

Ketone bodies and ketones are not the same

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 on the edge of the molecule. Officially called "a non-terminal carbonyl group". There are an incredible number of variants of such molecules, such ketones. But there are only three ketone bodies and they get their name from the fact that acetoacetate and acetone each have a “non-terminal carbonyl group” in their chemical structure. So: 2 ketone bodies belong to the class of ketones, but not all ketones are ketone bodies. (No matter how promising raspberry ketones are, they have absolutely nothing to do with ketosis.)

β-Hydroxybutyrate is chemically not a ketone because the keto group has been reduced (converted) to a hydroxyl group. Nevertheless, it is counted among the ketone bodies, because it can be quickly converted from acetoacetate and has comparable properties in the body. In addition, it is the most common of the ketone bodies and is the most important ketone body in the metabolism.

Some ketone bodies are excreted in the urine and breath

β-Hydroxybutyrate is converted from acetoacetate by enzymes. Acetone, on the other hand, is produced by the spontaneous breakdown of acetoacetate, without enzymes. It is volatile and is practically not used in the metabolism. Instead, it is mainly released through the lungs with the exhaled air. This is responsible for the sweetish bad breath.

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

Even without ketosis, the liver is constantly producing small amounts of ketone bodies

With normal, non-ketogenic metabolism in healthy people, small amounts of ketone bodies are continuously synthesized by the liver and consumed by other organs. The concentration of acetoacetone and β-hydroxybutyrate is about 0.01 mmol per liter of blood after a meal. Even after fasting at night, their concentration in the blood is still relatively low at 0.1 mmol / L. It only rises gradually when there is continued abstinence from food and reaches 2 mmol / L after about three days of fasting and about 5 mmol / L after a week without food. In this area one speaks of ketosis.

The blood sugar level is at the lower end of the physiological concentration during ketosis, maintained by gluconeogenesis from amino acids and glycerol. Gluconeogenesis is the construction of glucose from molecules that are not carbohydrates, such as amino acids from proteins or from glycerine a part of the triglycerides, the fats.

Ketosis is a completely physiological metabolic state

Ketosis, a physiological (normal and healthy) condition when there is no food, must not be confused with ketoacidosis, a pathological (pathological) condition that occurs in diabetes and alcohol abuse and can be life-threatening. In uncontrolled type I diabetes, the ketone body concentration can rise to 25 mmol / L, which leads to dangerous ketoacidosis. The buffer mechanisms of the blood, which normally take care of the acid-base balance, are overloaded and the blood becomes acidic. If a healthy person fasts or eats a very low-carbohydrate diet, such harmful values ​​will not be reached.

It was the biochemist Hans Krebs (discoverer of the Krebs cycle aka citrate cycle) who was the first to speak of “physiological ketosis” as a distinction to diabetic ketoacidosis. In a physiological context, increased ketone body concentrations do not only occur during fasting, but also with carbohydrate-limited, so-called "ketogenic diets".

Small amounts of insulin or glucose can quickly kill ketosis

The metabolic state of ketosis is very fragile and can be quickly stopped by giving insulin or glucose. Especially in the beginning, when the liver and other organs are just starting to adapt and are learning to produce and use ketone bodies. Carbohydrate intake leads to insulin being released. Insulin inhibits ketone body production and causes ketone bodies to be excreted in the urine. A high amount of protein also leads to insulin secretion, but does not have such a strong effect on ketosis. Because when protein is absorbed, glucagon, the antagonist of insulin, is released at the same time.

Ketone bodies carry energy through the blood

The small ketone bodies are high-energy compounds. There is also a lot of energy in fat. But what happens if you want to mix water and fat together? Doesn't quite work. Since most of our blood consists of water, it is also a bad idea to want to dissolve fat in it to transport energy from A to B. That's why 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 water-soluble. Unlike fat, they can easily be transported in the blood. In the evolution of humans, the ability to ketogenesis (production of ketone bodies) and ketolysis (utilization of ketone bodies) made it possible to survive in long periods of hunger, as the fat reserves of the ever-growing brains of human ancestors were able to provide an energy source.

Swell:

Cahill GF, Veech RL. 2003. Ketoacids Good Medicine. Trans Am Clin Climatol Assoc, 114: 149-161.

Fronzo R de, Ferrannini E. 2001. Regulation of Intermediary Metabolism During Fasting and Feeding. In: DeGroot LJ, Jameson JL. Endocrinology. Sixth Ed. Philadelphia: W.B. Saunders, 735-755.

Fukao T, Lopaschuk GD, Mitchell GA. 2004. Pathways and Control of Ketone Body Metabolism on the Fringe of Lipid Biochemistry. Prostaglandins Leukot Essent Fatty Acids, 70 (3): 243-251.

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

Page MM, Alberti KG, Greenwood R, Gumaa KA, Hockaday TD, Lowy C, Nabarro JD, Pyke DA, Sönksen PH, Watkins PJ, West TE. 1974. Treatment of Diabetic Coma with Continuous Low-Dose Infusion of Insulin. Br Med J, 2 (5921): 687-690.

Rehner G, Daniel H. 2010. Biochemistry of Nutrition. Third edition Heidelberg: Spektrum Akademischer Verlag, 471-475.

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