“In biology, ketosis (pronounced /kɪˈtəʊsɪs/) is a state of the organism characterised by elevated levels of ketone bodies in the blood, occurring when the liver converts fat into fatty acids and ketone bodies (which can be used for energy as an alternative to glucose).
Ketone bodies, from the breakdown of fatty acids to acetyl groups, are also produced during this state, and are burned throughout the body.[clarification needed] Excess ketone bodies will slowly decarboxylate into acetone. That molecule is excreted in the breath and urine.
When glycogen stores are not available in the cells (glycogen is primarily created when carbohydrates such as starch and sugar are consumed in the diet), fat (triacylglycerol) is cleaved to give 3 fatty acid chains and 1 glycerol molecule in a process called lipolysis. Most of the body is able to utilize fatty acids as an alternative source of energy in a process where fatty acid chains are cleaved to form acetyl-CoA, which can then be fed into the Krebs Cycle. It is important to note that acetyl-CoA can only enter the Krebs Cycle bound to oxaloacetate. When carbohydrate supplies are inadequate, however, the liver naturally converts oxaloacetate to glucose via gluconeogenesis for use by the brain and other tissues. When acetyl CoA does not bind with oxaloacetate, the liver converts it to ketones (or ketone bodies), leading to a state of ketosis. During this process a high concentration of glucagon is present in the serum and this inactivates hexokinase and phosphofructokinase-1 (regulators of glycolysis) indirectly, causing most cells in the body to use fatty acids as their primary energy source. At the same time, glucose is synthesized in the liver from lactic acid, glucogenic amino acids, and glycerol, in a process called gluconeogenesis. This glucose is used exclusively[clarification needed] for energy by cells such as neurons and red blood cells.
Ketosis should not be confused with ketoacidosis (diabetic ketoacidosis or the less common alcoholic ketoacidosis), which is severe ketosis causing the pH of the blood to drop below 7.2. Ketoacidosis is a medical condition usually caused by diabetes and accompanied by dehydration, hyperglycemia, ketonuria and increased levels of glucagon. The high glucagon, low insulin serum levels signals the body to produce more glucose via gluconeogenesis and glycogenolysis, and ketone bodies via ketogenesis. High levels of glucose causes the failure of tubular reabsorption in the kidneys, causing water to leak into the tubules in a process called osmotic diuresis, causing dehydration and further exacerbating the acidosis.
If the diet is changed from a highly glycemic diet to a diet that does not provide sufficient carbohydrate to replenish glycogen stores, the body goes through a set of stages to enter ketosis. During the initial stages of this process the adult brain does not burn ketones; however, the brain makes immediate use of this important substrate for lipid synthesis in the brain. After about 48 hours of this process, the brain starts burning ketones in order to more directly utilize the energy from the fat stores that are being depended upon, and to reserve the glucose only for its absolute needs, thus avoiding the depletion of the body’s protein store in the muscles.
Whether ketosis is taking place can be checked by using special urine test strips such as Ketostix.
Ketosis is deliberately induced in the ketogenic diet used to treat epilepsy. Other uses of low-carbohydrate diets remain controversial.
Some medical resources regard ketosis as a physiological state associated with chronic starvation. Some clinicians regard ketosis as a crisis reaction of the body due to a lack of carbohydrates in the diet and consider it a dangerous and potentially life-threatening state that stresses the liver and causes destruction of muscle tissues. It should be remembered from the above discussion that ketogenesis does not destroy muscle tissue. Ketogenesis can occur solely from the byproduct of fat degradation: acetyl-CoA. Ketosis, which is accompanied by gluconeogenesis (the creation of de novo glucose from amino acids), is the specific state with which clinicians are concerned.
The anti-ketosis conclusions have been challenged by a number of doctors and adherents of low-carbohydrate diets, who dispute assertions that the body has a preference for glucose and that there are dangers associated with ketosis. It has been argued that not only did hunter societies live for thousands of years in a primarily ketogenic state, but also that there are many documented cases of modern humans living in these societies for extended periods of time. While it is believed by some that exercise requires carbohydrate intake in order to replace depleted glycogen stores, studies have shown that after a period of 2–4 weeks adaptation, physical endurance is unaffected by ketosis.