ketone bodies


Summary: The metabolic substances ACETONE; 3-HYDROXYBUTYRIC ACID; and acetoacetic acid (ACETOACETATES). They are produced in the liver and kidney during FATTY ACIDS oxidation and used as a source of energy by the heart, muscle and brain.

Top Publications

  1. Morris A. Cerebral ketone body metabolism. J Inherit Metab Dis. 2005;28:109-21 pubmed
    b>Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids...
  2. Montgomery C, Pei Z, Watkins P, Miziorko H. Identification and characterization of an extramitochondrial human 3-hydroxy-3-methylglutaryl-CoA lyase. J Biol Chem. 2012;287:33227-36 pubmed publisher
    ..The available results for COS1 cell expression, as well as endogenous expression in U87 cells, indicate that HMGCLL1 is an extramitochondrial hydroxymethylglutaryl-CoA lyase...
  3. Hugo S, Cruz Garcia L, Karanth S, Anderson R, Stainier D, Schlegel A. A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting. Genes Dev. 2012;26:282-93 pubmed publisher
    ..Since ?-hydroxybutyrate is both a major fuel and a signaling molecule in fasting, the discovery of this transporter provides a new direction for modulating circulating levels of ketone bodies in metabolic diseases.
  4. Tamaru S, Kurayama T, Sakono M, Fukuda N, Nakamori T, Furuta H, et al. Effects of dietary soybean peptides on hepatic production of ketone bodies and secretion of triglyceride by perfused rat liver. Biosci Biotechnol Biochem. 2007;71:2451-7 pubmed
    ..There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution. ..
  5. Yang L, Zhao J, Milutinovic P, Brosnan R, Eger E, Sonner J. Anesthetic properties of the ketone bodies beta-hydroxybutyric acid and acetone. Anesth Analg. 2007;105:673-9 pubmed
    ..Beta hydroxybutyric acid and acetone are anesthetics. Both ketone bodies enhance inhibitory glycine receptors at concentrations observed clinically in ketoacidosis...
  6. Prins M. Cerebral metabolic adaptation and ketone metabolism after brain injury. J Cereb Blood Flow Metab. 2008;28:1-16 pubmed
    The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the 'post-weaned/adult' brain was limited solely to glucose metabolism...
  7. Szymanski L, Schneider J, Friedman M, Ji H, Kurose Y, Blache D, et al. Changes in insulin, glucose and ketone bodies, but not leptin or body fat content precede restoration of luteinising hormone secretion in ewes. J Neuroendocrinol. 2007;19:449-60 pubmed
    ..Prior to the initial LH pulses seen in Re-Fed ewes, plasma ketone bodies first fell and then rose to levels significantly above those in Restricted ewes...
  8. Kim D, Davis L, Sullivan P, Maalouf M, Simeone T, van Brederode J, et al. Ketone bodies are protective against oxidative stress in neocortical neurons. J Neurochem. 2007;101:1316-26 pubmed
    b>Ketone bodies (KB) have been shown to prevent neurodegeneration in models of Parkinson's and Alzheimer's diseases, but the mechanisms underlying these effects remain unclear. One possibility is that KB may exert antioxidant activity...
  9. Gasior M, French A, Joy M, Tang R, Hartman A, Rogawski M. The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid. Epilepsia. 2007;48:793-800 pubmed
    Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet...

More Information


  1. Rheims S, Holmgren C, Chazal G, Mulder J, Harkany T, Zilberter T, et al. GABA action in immature neocortical neurons directly depends on the availability of ketone bodies. J Neurochem. 2009;110:1330-8 pubmed publisher
    ..rodent brain relies to a large extent on metabolic pathways alternate to glucose such as the utilization of ketone bodies (KBs). However, how KBs affect neuronal excitability is not known...
  2. Pelletier A, Tardif A, Gingras M, Chiasson J, Coderre L. Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes in response to insulin but not vanadate: the role of PI3-K. Mol Cell Biochem. 2007;296:97-108 pubmed
    ..In conclusion, ketone bodies promote insulin resistance probably through decreased activation of the PI3-K/PKB signaling cascade...
  3. Maalouf M, Rho J. Oxidative impairment of hippocampal long-term potentiation involves activation of protein phosphatase 2A and is prevented by ketone bodies. J Neurosci Res. 2008;86:3322-30 pubmed publisher
    Previous studies have shown that ketone bodies (KB) exert antioxidant effects in experimental models of neurological disease...
  4. Costantini L, Barr L, Vogel J, Henderson S. Hypometabolism as a therapeutic target in Alzheimer's disease. BMC Neurosci. 2008;9 Suppl 2:S16 pubmed publisher
    ..b>Ketone bodies are an efficient alternative fuel for cells that are unable to metabolize glucose or are 'starved' of glucose...
  5. Pelletier A, Coderre L. Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes. Am J Physiol Endocrinol Metab. 2007;292:E1325-32 pubmed
    ..Thus abnormal regulation of glucose uptake may contribute to the development of cardiac disease in diabetics. Ketone bodies are often elevated in poorly controlled diabetics and are associated with increased cellular oxidative stress...
  6. Martinez Outschoorn U, Goldberg A, Lin Z, Ko Y, Flomenberg N, Wang C, et al. Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells. Cancer Biol Ther. 2011;12:924-38 pubmed publisher
    ..Treatment of MCF7 cells cultured alone with high-energy mitochondrial "fuels" (L-lactate or ketone bodies) is sufficient to confer tamoxifen resistance, mimicking the effects of coculture with fibroblasts...
  7. Musa Veloso K, Likhodii S, Rarama E, Benoit S, Liu Y, Chartrand D, et al. Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet. Nutrition. 2006;22:1-8 pubmed
  8. Smith S, Heal D, Martin K. KTX 0101: a potential metabolic approach to cytoprotection in major surgery and neurological disorders. CNS Drug Rev. 2005;11:113-40 pubmed
    ..These issues are being addressed by designing and synthesizing orally bioavailable multimers of betaOHB with improved pharmacokinetics...
  9. Henderson S. Ketone bodies as a therapeutic for Alzheimer's disease. Neurotherapeutics. 2008;5:470-80 pubmed publisher
    ..One promising approach is to supplement the normal glucose supply of the brain with ketone bodies (KB), which include acetoacetate, beta-hydroxybutyrate, and acetone...
  10. Waddell J, Kim J, Alger B, McCarthy M. The depolarizing action of GABA in cultured hippocampal neurons is not due to the absence of ketone bodies. PLoS ONE. 2011;6:e23020 pubmed publisher
    ..The authors argue that this does not mimic the physiological environment because the suckling rats use ketone bodies and pyruvate as major sources of metabolic energy...
  11. Ben Ari Y, Tyzio R, Nehlig A. Excitatory action of GABA on immature neurons is not due to absence of ketone bodies metabolites or other energy substrates. Epilepsia. 2011;52:1544-58 pubmed publisher
    ..that ?-aminobutyric acid (GABA) excites neonatal neurons in conventional glucose-perfused slices but not when ketone bodies metabolites, pyruvate, and/or lactate are added, suggesting that the excitatory actions of GABA are due to ..
  12. Melø T, Nehlig A, Sonnewald U. Neuronal-glial interactions in rats fed a ketogenic diet. Neurochem Int. 2006;48:498-507 pubmed
    ..However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels...
  13. Yamato S, Shinohara K, Nakagawa S, Kubota A, Inamura K, Watanabe G, et al. High-performance liquid chromatography determination of ketone bodies in human plasma by precolumn derivatization with p-nitrobenzene diazonium fluoroborate. Anal Biochem. 2009;384:145-50 pubmed publisher
    ..and convenient high-performance liquid chromatography (HPLC) method for the specific determination of ketone bodies (acetoacetate and D-3-hydroxybutyrate) in human plasma...
  14. McPherson P, McEneny J. The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress. J Physiol Biochem. 2012;68:141-51 pubmed publisher
    Ketogenesis is the branch of mammalian metabolism concerned with the synthesis of ketone bodies. In this process, the small, water-soluble compounds acetoacetate, D-3-?-hydroxybutyrate and propanone are produced by the liver in response ..
  15. Skinner R, Trujillo A, Ma X, Beierle E. Ketone bodies inhibit the viability of human neuroblastoma cells. J Pediatr Surg. 2009;44:212-6; discussion 216 pubmed publisher
    ..tumor cells, unlike normal brain cells, are largely dependent upon glucose for energy and are not able to use ketone bodies as a primary energy source...
  16. Tyzio R, Allene C, Nardou R, Picardo M, Yamamoto S, Sivakumaran S, et al. Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate. J Neurosci. 2011;31:34-45 pubmed publisher
    ..There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain. ..
  17. Faria M, Muniz L, Vasconcelos P. Ketone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in rats. Acta Cir Bras. 2007;22:125-9 pubmed
    To evaluate the in vivo alterations on ketone bodies metabolism after cerebral ischemia/reperfusion through an experimental model of brain ischemia induced by simple occlusion of common carotid arteries (CCAs) in Wistar rats...
  18. Kirmse K, Witte O, Holthoff K. GABA depolarizes immature neocortical neurons in the presence of the ketone body ß-hydroxybutyrate. J Neurosci. 2010;30:16002-7 pubmed publisher
    ..Our data thereby support the general concept of an excitatory-to-inhibitory switch of GABA action during early development. ..
  19. Holmgren C, Mukhtarov M, Malkov A, Popova I, Bregestovski P, Zilberter Y. Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro. J Neurochem. 2010;112:900-12 pubmed publisher
    ..Complementing glucose with ketone bodies, pyruvate or lactate resulted in a significant hyperpolarization of both E(m) and E(GABA), and induced a ..
  20. Chearskul S, Delbridge E, Shulkes A, Proietto J, Kriketos A. Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations. Am J Clin Nutr. 2008;87:1238-46 pubmed
    ..impedance, body weight, and waist circumference), concentrations of circulating hormones and metabolites [ketone bodies, free fatty acids (FFAs), insulin, leptin, glucose, and cholecystokinin (CCK)], and measures of hunger and ..
  21. Prisco F, Picardi A, Iafusco D, Lorini R, Minicucci L, Martinucci M, et al. Blood ketone bodies in patients with recent-onset type 1 diabetes (a multicenter study). Pediatr Diabetes. 2006;7:223-8 pubmed
    Insulin deficiency with glucagon excess leads to the release of ketone bodies (KBs) by the liver and excretion in the urine. So far, only KB monitoring in urine has been used during assessment of children with diabetes...
  22. Martin P, Gopal E, Ananth S, Zhuang L, Itagaki S, Prasad B, et al. Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain. J Neurochem. 2006;98:279-88 pubmed
    ..Here, we show that the ketone bodies, beta-d-hydroxybutyrate and acetoacetate, and the branched-chain ketoacid, alpha-ketoisocaproate, are also ..
  23. Martinez Outschoorn U, Lin Z, Whitaker Menezes D, Howell A, Lisanti M, Sotgia F. Ketone bodies and two-compartment tumor metabolism: stromal ketone production fuels mitochondrial biogenesis in epithelial cancer cells. Cell Cycle. 2012;11:3956-63 pubmed publisher
    ..In addition, treatment with ketone bodies (such as 3-hydroxy-butyrate, and/or butanediol) is sufficient to drive mitochondrial biogenesis in human ..
  24. Seyfried T, Kiebish M, Mukherjee P, Marsh J. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets. Epilepsia. 2008;49 Suppl 8:114-6 pubmed publisher
    ..In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic ..
  25. Maalouf M, Rho J, Mattson M. The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 2009;59:293-315 pubmed publisher
    ..partially, the neuroprotective effects of the diets with less demanding changes to food intake suggests that ketone bodies might represent an appropriate candidate...
  26. Samoilova M, Weisspapir M, Abdelmalik P, Velumian A, Carlen P. Chronic in vitro ketosis is neuroprotective but not anti-convulsant. J Neurochem. 2010;113:826-35 pubmed publisher
    ..Yet, a direct role for ketone bodies in limiting seizure and neuronal damage remains poorly understood...
  27. Finn P, Dice J. Ketone bodies stimulate chaperone-mediated autophagy. J Biol Chem. 2005;280:25864-70 pubmed
    ..b>Ketone bodies are comprised of three compounds (beta-hydroxybutyrate, acetoacetate, and acetone) that circulate during ..
  28. Garai J, Lorand T, Molnar V. Ketone bodies affect the enzymatic activity of macrophage migration inhibitory factor. Life Sci. 2005;77:1375-80 pubmed
    ..Ketones of physiological importance - ketone bodies - also feature acidic CH groups and have been reported to exert certain anti-inflammatory effects...
  29. Zhao Z, Lange D, Voustianiouk A, MacGrogan D, Ho L, Suh J, et al. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 2006;7:29 pubmed
    ..These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.
  30. Puchowicz M, Zechel J, Valerio J, Emancipator D, Xu K, Pundik S, et al. Neuroprotection in diet-induced ketotic rat brain after focal ischemia. J Cereb Blood Flow Metab. 2008;28:1907-16 pubmed publisher
  31. Yellen G. Ketone bodies, glycolysis, and KATP channels in the mechanism of the ketogenic diet. Epilepsia. 2008;49 Suppl 8:80-2 pubmed publisher
    ..Several hypotheses focus on ketone bodies, fuel molecules that circulate at millimolar concentrations in the blood of patients on a KD, as causative ..
  32. Paik M, Cho E, Kim H, Kim K, Choi S, Ahn Y, et al. Simultaneous clinical monitoring of lactic acid, pyruvic acid and ketone bodies in plasma as methoxime/tert-butyldimethylsilyl derivatives by gas chromatography-mass spectrometry in selected ion monitoring mode. Biomed Chromatogr. 2008;22:450-3 pubmed publisher
    ..2-7.6), with detection limits of 0.05-1.7 ng/mL. This rapid, accurate and selective method using minimal plasma samples (20 microL) is useful in the clinical monitoring of lactic acidosis and ketone body formation in plasma. ..
  33. MacDonald M, Longacre M, Stoker S, Brown L, Hasan N, Kendrick M. Acetoacetate and beta-hydroxybutyrate in combination with other metabolites release insulin from INS-1 cells and provide clues about pathways in insulin secretion. Am J Physiol Cell Physiol. 2008;294:C442-50 pubmed
    ..The pathways of their metabolism suggest that, in addition to producing ATP, the ketone bodies and KIC supply the acetate component and MMS supplies the oxaloacetate component of citrate...
  34. Dresing K, Armstrong V, Leip C, Streit F, Burchardi H, Stürmer K, et al. Real-time assessment of hepatic function is related to clinical outcome in critically ill patients after polytrauma. Clin Biochem. 2007;40:1194-200 pubmed
    ..61 microg/L; p=0.05). The MEGX test and AKBR are sensitive early indicators of hepatic dysfunction in severely injured polytrauma patients at risk for developing MODS/MOF. ..
  35. Srivastava S, Kashiwaya Y, King M, Baxa U, Tam J, Niu G, et al. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. FASEB J. 2012;26:2351-62 pubmed publisher
    ..The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement. ..
  36. Gasior M, Rogawski M, Hartman A. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol. 2006;17:431-9 pubmed
    ..These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially beta-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury...
  37. Imamura K, Takeshima T, Kashiwaya Y, Nakaso K, Nakashima K. D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease. J Neurosci Res. 2006;84:1376-84 pubmed
    ..b>Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD.
  38. Park S, Kim D, Daily J. Central infusion of ketone bodies modulates body weight and hepatic insulin sensitivity by modifying hypothalamic leptin and insulin signaling pathways in type 2 diabetic rats. Brain Res. 2011;1401:95-103 pubmed publisher
    ..In conclusion, mild ketosis by central infusion of ketones improves energy and glucose metabolism through the potentiation of leptin and insulin signaling in the hypothalamus of diabetic rats. ..
  39. Haces M, Hernández Fonseca K, Medina Campos O, Montiel T, Pedraza Chaverri J, Massieu L. Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions. Exp Neurol. 2008;211:85-96 pubmed publisher
    b>Ketone bodies play a key role in mammalian energy metabolism during the suckling period...
  40. McNally M, Hartman A. Ketone bodies in epilepsy. J Neurochem. 2012;121:28-35 pubmed publisher
    ..The diet received its name based on the observation that patients consuming this diet produce ketone bodies (e.g., acetoacetate, ?-hydroxybutyrate, and acetone)...
  41. Maurer G, Brucker D, Bähr O, Harter P, Hattingen E, Walenta S, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer. 2011;11:315 pubmed publisher
    ..Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells...
  42. Yao J, Chen S, Mao Z, Cadenas E, Brinton R. 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer's disease. PLoS ONE. 2011;6:e21788 pubmed publisher
    ..Collectively, these data provide preclinical evidence for dietary 2-DG as a disease-modifying intervention to delay progression of bioenergetic deficits in brain and associated ?-amyloid burden. ..
  43. van Poelje P, Potter S, Chandramouli V, Landau B, Dang Q, Erion M. Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in Zucker diabetic fatty rats. Diabetes. 2006;55:1747-54 pubmed
    ..The studies confirm that excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes and suggest that FBPase inhibitors may provide a future treatment option. ..
  44. Yao J, Hamilton R, Cadenas E, Brinton R. Decline in mitochondrial bioenergetics and shift to ketogenic profile in brain during reproductive senescence. Biochim Biophys Acta. 2010;1800:1121-6 pubmed publisher
    ..These findings provide a plausible mechanism for increased life-time risk of AD in postmenopausal women and suggest an optimal window of opportunity to prevent or delay decline in bioenergetics during reproductive senescence. ..
  45. Hotta Y, Nakamura H, Konishi M, Murata Y, Takagi H, Matsumura S, et al. Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver. Endocrinology. 2009;150:4625-33 pubmed publisher
    ..The present results indicate that Fgf21 regulates lipolysis in adipocytes in response to the metabolic state but is not required for ketogenesis and triglyceride clearance in the liver. ..
  46. Bough K, Rho J. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007;48:43-58 pubmed
    ..gleaned from experimental and clinical studies of the KD, and focus particular attention on the role that ketone bodies, fatty acids, and limited glucose may play in seizure control...
  47. Soeters M, Sauerwein H, Faas L, Smeenge M, Duran M, Wanders R, et al. Effects of insulin on ketogenesis following fasting in lean and obese men. Obesity (Silver Spring). 2009;17:1326-31 pubmed publisher
    The ketone bodies (KBs) D-3-hydroxybutyrate (D-3HB) and acetoacetate (AcAc) play a role in starvation and have been associated with insulin resistance...
  48. Freemantle E, Vandal M, Tremblay Mercier J, Plourde M, Poirier J, Cunnane S. Metabolic response to a ketogenic breakfast in the healthy elderly. J Nutr Health Aging. 2009;13:293-8 pubmed
    ..Elderly people in relatively good health have a similar capacity to produce ketones and to oxidize 13C-beta-hydroxybutyrate as middle-aged or young adults, but oxidize 13C-glucose a little more rapidly than healthy middle-aged adults. ..
  49. Reger M, Henderson S, Hale C, Cholerton B, Baker L, Watson G, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging. 2004;25:311-4 pubmed
    ..Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain...
  50. Seyfried T, Sanderson T, El Abbadi M, McGowan R, Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer. 2003;89:1375-82 pubmed
    ..This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and ..
  51. Guzman M, Blazquez C. Is there an astrocyte-neuron ketone body shuttle?. Trends Endocrinol Metab. 2001;12:169-73 pubmed
    b>Ketone bodies can replace glucose as the major source of brain energy when glucose becomes scarce...
  52. Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999;15:412-26 pubmed
    b>Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available...
  53. Lukivskaya OYa -, Buko V. Utilization of ketone bodies by the rat liver, brain and heart in chronic alcohol intoxication. Alcohol Alcohol. 1993;28:431-6 pubmed
    ..The data obtained indicate both disturbed ketone body utilization and increased importance of acetate produced from ethanol as an energy source in the heart during long-term ethanol treatment. ..