Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiologic ketosis is a normal response to low glucose availability, such as low-carbohydrate diets or fasting, that provides an additional energy source for the brain in the form of ketones. In physiologic ketosis, ketones in the blood are elevated above baseline levels but the body's acid-base homeostasis is maintained. This contrasts with ketoacidosis, an uncontrolled production of ketones that occurs in pathologic states and causes a metabolic acidosis, which is a medical emergency. Ketoacidosis is most commonly the result of complete insulin deficiency in type 1 diabetes or late-stage type 2 diabetes. Ketone levels can be measured in blood, urine or breath and are generally between 0.5 and 3.0 mM in physiologic ketosis while ketoacidosis may cause blood concentrations >10 mM.
Trace levels of ketones are always present in the blood and increase when blood glucose reserves are low and the liver shifts from primarily metabolizing carbohydrates to metabolizing fatty acids. This occurs during states of increased fatty acid oxidation such as fasting, starvation, carbohydrate restriction, or prolonged exercise. When the liver rapidly metabolizes fatty acids into acetyl-CoA, some acetyl-CoA molecules can then be converted into ketone bodies: acetoacetate, beta-hydroxybutyrate, and acetone. These ketone bodies can function as an energy source as well as signalling molecules. The liver itself cannot utilize these molecules for energy so the ketone bodies are released into the blood for use by peripheral tissues including the brain.
When ketosis is induced by carbohydrate restriction, it is sometimes referred to as nutritional ketosis. A low-carbohydrate, moderate protein diet that can lead to ketosis is called a ketogenic diet. Nutritional ketosis alone does not progress to ketoacidosis and its safety is supported in trials up to two years, although research on longer term ketosis is lacking. Ketosis is well-established as a treatment for epilepsy and is also effective in treating type 2 diabetes. Benefit in a range of neurological diseases, metabolic syndrome, cancer, and other conditions is currently under investigation.
Ketones are substances closely allied to acetone, or dimethyl ketone, especially beta-hydroxybutyric acid and acetoacetic acid. These are produced in the body from imperfect oxidation of fats and protein foods. A ketogenic diet is one containing such an excess of fats that acetone and other ketones appear in the urine (ketonuria). It is sometimes used in the treatment of epilepsy and chronic infections of the urinary tract by Escherichia coli. In this diet, butter, cream, eggs and fat meat are allowed, whilst sugar, bread, and other carbohydrates are cut out as far as possible.
Ketosis is one of the symptoms of diabetes; if untreated, a state of coma may ensue and the disease end fatally. It also occurs in the terminal stages of Bright's disease when it is due to failure of the kidneys.