ketosis

Ketosis
Classification and external resources
Ketone bodies
ICD-9	276.2
DiseasesDB	29485
MeSH	D007662

Ketosis ( /kɨˈtoʊsɨs/) is a state of elevated levels of ketone bodies in the body.^[1] It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted. The ketone bodies acetoacetate and β-hydroxybutyrate are used for energy. ^[2]

Metabolic pathways

When glycogen stores are not available in the cells, 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 use fatty acids as an alternative source of energy in a process called beta-oxidation. One of the products of beta-oxidation is acetyl-CoA, which can be further used in the Krebs cycle. During prolonged fasting or starvation, acetyl-CoA in the liver is used to produce ketone bodies instead, leading to a state of ketosis.

During starvation or a long physical training session, the body starts using fatty acids instead of glucose. The brain cannot use long-chain fatty acids for energy because they are completely albumin-bound and cannot cross the blood-brain barrier. Not all medium-chain fatty acids are bound to albumin. The unbound medium-chain fatty acids are soluble in the blood and can cross the blood-brain barrier.[2] The ketone bodies produced in the liver can also cross the blood-brain barrier. In the brain, these ketone bodies are then incorporated into acetyl-CoA and used in the citric acid cycle.

The ketone body acetoacetate will slowly decarboxylate into acetone, a volatile compound that is both metabolized as an energy source and lost in the breath and urine.

Ketoacidosis

Ketone bodies are acidic, but acid-base homeostasis in the blood is normally maintained through bicarbonate buffering, respiratory compensation to vary the amount of CO₂ in the bloodstream, hydrogen ion absorption by tissue proteins and bone, and renal compensation through increased excretion of dihydrogen phosphate and ammonium ions.^[3] Prolonged excess of ketone bodies can overwhelm normal compensatory mechanisms, leading to acidosis if blood pH falls below 7.35.

There are two major causes of ketoacidosis:

• Most commonly, ketoacidosis is diabetic ketoacidosis (DKA), resulting from increased fat metabolism due to a shortage of insulin. It is associated primarily with type I diabetes, and may result in a diabetic coma if left untreated.^[4]

• Alcoholic ketoacidosis (AKA) presents infrequently, but can occur with acute alcohol intoxication, most often following a binge in alcoholics with acute or chronic liver or pancreatic disorders. Alcoholic ketoacidosis occurs more frequently following methanol or ethylene glycol intoxication than following intoxication with uncontaminated ethanol.^[5]

A mild acidosis may result from prolonged fasting or when following a ketogenic diet.^[6]

Diet

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, blood glucose levels are maintained through gluconeogenesis, and the adult brain does not burn ketones. However, the brain makes immediate use of ketones for lipid synthesis in the brain. After about 48 hours of this process, the brain starts burning ketones in order to more directly use 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.^[7]

Ketosis is deliberately induced by use of a ketogenic diet as a medical intervention in cases of intractable epilepsy.^[6] Other uses of low-carbohydrate diets remain controversial.^[8][9]

Diagnosis

Whether ketosis is taking place can be checked by using special urine test strips such as Ketostix. The strips have a small pad on the end which is dipped in a fresh specimen of urine. Within a matter of seconds, the strip changes color indicating the level of ketone bodies detected, which reflects the degree of ketonuria, which, in turn, can be used to give a rough estimation of the level of hyperketonemia in the body (see table below). Normal serum reference ranges for ketone bodies are 0.5-3.0 mg/dL, equivalent to 0.05-0.29 mmol/L.^[10]

Also, when the body is in ketosis, subjects often smell of acetone. Some find the smell offensive as acetone is the same chemical responsible for the smell in paint thinner and nail polish remover.

Controversy

Some clinicians regard ketosis as a dangerous and potentially life-threatening state that stresses the liver ^{[15][dubious – discuss]}, while on the other hand, many regard it as a safe biochemical process that occurs during the the fat-burning state. Ketogenesis can occur solely from the byproduct of fat degradation: acetyl-CoA. Ketosis, which is accompanied by gluconeogenesis (the creation of glucose de novo from pyruvate), is the specific state with which some clinicians are concerned. It must be noted, however, that it is unlikely for a normal functioning person to reach life-threatening levels of ketosis. This is avoided with proper basal secretion of pancreatic insulin. People who are unable to secrete basal insulin, such as type I diabetics and long-term type II diabetics, are liable to enter an unsafe level of ketosis, causing an eventual comatose state that requires emergency medical treatment.

The anti-ketosis conclusions have been challenged by a number of doctors and advocates of low-carbohydrate diets, who dispute assertions that the body has a preference for glucose and that there are dangers associated with ketosis.^[16][17][18] It has been argued that the Inuit lived for thousands of years on a diet that would have been ketogenic, and there are many documented cases of modern humans living in these societies for extended periods of time. On the other hand, it is speculated by Nick Lane ^[19] that the Inuit may have a genetic predisposition allowing them to healthfully eat a ketogenic diet. According to this view, such an evolutionary adaptation would have been caused by environmental stresses.^[20] While it is believed that carbohydrate intake after exercise is the most effective way of replacing depleted glycogen stores,^[21][22] studies have shown that, after a period of 2–4 weeks of adaptation, physical endurance (as opposed to physical intensity) is unaffected by ketosis, as long as the diet contains high amounts of fat.^[20]

See also

• Ketoacidosis
• Ketogenic diet
• Ketonuria
• Low-carbohydrate diet
• Fasting
• Ketogenesis

References

External links

• Diabetic Ketoacidosis at eMedicine
• NHS Direct: Ketosis
• Musa-Veloso K, Likhodii SS, Cunnane SC (July 2002). "Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals". Am. J. Clin. Nutr. 76 (1): 65–70. PMID 12081817. http://www.ajcn.org/cgi/content/full/76/1/65. 
• The Merck Manual —
  • Diabetic Ketoacidosis
  • Alcoholic Ketoacidosis