Ketosis
| Ketosis | |
|---|---|
| Specialty | Endocrinology  |
In biology, ketosis (Template:Pron-en) is a state of the organism characterised by elevated levels of ketone bodies in the blood, by the process of ketogenesis. Ketone bodies are formed when the liver glycogen stores are depleted. The ketone bodies acetoacetate and ß-hydroxybutyrate are used for energy. [1]
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 utilize 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.
Acetyl-CoA reacts with oxaloacetate as it enters the Krebs cycle. When carbohydrate supplies are inadequate to maintain blood glucose levels, the liver naturally converts oxaloacetate in the liver to glucose via gluconeogenesis for use by the brain and other tissues. Excess acetyl-CoA in the liver is used to produce ketone bodies, leading to a state of ketosis. During this process, a high concentration of glucagon is present in the serum, which inactivates hexokinase and phosphofructokinase-1 (regulators of glycolysis) indirectly, causing most cells in the body to use fatty acids as their primary energy source.
The brain cannot use fatty acids for energy because the fatty acids cannot cross the blood-brain barrier. However, the ketone bodies produced in the liver can cross the blood-brain barrier. In the brain, these ketone bodies are then incorporated into acetyl-CoA and used in the Krebs cycle.
Excess ketone bodies will slowly decarboxylate into acetone. Acetone is excreted in the breath and urine.
Ketoacidosis
All ketone bodies are acidic, but during normal conditions the blood can buffer to keep the pH of the blood within normal range. Severe ketosis which causes blood pH to drop below 7.35 can occur as an effect of diabetes or alcohol poisoning, causing an acidosis, more specifically ketoacidosis.
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 signal 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.
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, 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.
Ketosis is deliberately induced in the ketogenic diet used to treat epilepsy. Other uses of low-carbohydrate diets remain controversial.[2][3]
Diagnosis
Whether ketosis is taking place can be checked by using special urine test strips such as Ketostix.
When the body is in ketosis, subjects often have a fruity breath, and a darkening of their urine. The subjects may smell of acetone.
Controversy
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.[4][5][6][dubious – discuss] 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.[7][8][9] 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.[10] 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[10].
See also
External links
- Diabetic Ketoacidosis
- NHS Direct: Ketosis
- Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals, American Journal of Clinical Nutrition.
- The Merck Manual -
References
- ^ Harvey & Champe, biochemistry
- ^ G.D Foster et al., NEJM2003;348:2082-90
- ^ Bravata et al., "Efficacy and safety of low-carbohydrate diets: a systematic review." Journal of the American Medical Association, Apr, 2003; 289(14):1837-50 [1]
- ^ High-Protein Diets, American Heart Association, 14 March 2008
- ^ [http://www.cancer.org/docroot/SPC/content/SPC_1_A_Low_Carb_Diet_to_Prevent_Cancer.asp Weighing In on Low-Carb Diets], The American Cancer Society, retrieved 12 March 2008
- ^ Karra, Cindy: Shape Up America! Reveals The Truth About Dieters, Shape Up America! (by former U.S. Surgeon General C. Everett Koop), 29 December 2003
- ^ Eaton, S. Boyd (31 January 1985). "Paleolithic nutrition: a consideration of its nature and current implications". New England Journal of Medicine. 312 (5): 283–89. PMID 2981409.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Eades, M. et al. Protein Power Lifeplan
- ^ William S Yancy, Jr, Marjorie Foy, Allison M Chalecki, Mary C Vernon, and Eric C Westman (2005). "A low-carbohydrate, ketogenic diet to treat type 2 diabetes". Journal of Nutrition and Metabolism. 2: 34. doi:10.1186/1743-7075-2-34.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Diets, Ketogenic; Performance
Jo, Physical; Nutrition, .; Metabolism
Ur, .; .; . N.; Impaired Physical Performance Is A. Common But Not Obligate Result Of A. Low Carbohydrate Diet. Lessons From Traditional Inuit Culture Indicate That Time For Adaptation, Optimized Sodium; Nutriture, Potassium; To, Constraint of Protein; .; Er, . of Daily Energy Expenditure Allow Unimpaired Endurance Performance Despite Nutritional Ketosis (2004). "TY - JOUR AU - Phinney, Stephen PY -". SN -. 1 (1): 1743–7075. doi:10.1186/1743-7075-1-2. Retrieved 2009-10-29.
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