What Are Ketone Bodies And Why Are They In The Body?
If you eat a calorie-restricted diet for several days, you will increase the breakdown of your fat stores. However, many of your tissues cannot convert these fatty acid products directly into ATP, or cellular energy. In addition, glucose is in limited supply and must be reserved for red blood cells -- which can only use glucose for energy -- and brain tissues, which prefer to use glucose. Therefore, your liver converts many of these fatty acids into ketone bodies, which circulate in the blood and provide a fuel source for your muscles, kidneys and brain. Video of the Day Low fuel levels in your body, such as during an overnight fast or while you are dieting, cause hormones to increase the breakdown of fatty acids from your stored fat tissue. These fatty acids travel to the liver, where enzymes break the fatty acids into ketone bodies. The ketone bodies are released into the bloodstream, where they travel to tissues that have the enzymes to metabolize ketone bodies, such as your muscle, brain, kidney and intestinal cells. The breakdown product of ketone bodies goes through a series of steps to form ATP. Conditions of Ketone Body Utilization Your liver will synthesize more ketone bodies for fuel whenever your blood fatty acid levels are elevated. This will happen in response to situations that promote low blood glucose, such as an overnight fast, prolonged calorie deficit, a high-fat and low-carbohydrate diet, or during prolonged low-intensity exercise. If you eat regular meals and do not typically engage in extremely long exercise sessions, the level of ketone bodies in your blood will be highest after an overnight fast. This level will drop when you eat breakfast and will remain low as long as you eat regular meals with moderate to high carbohydrate content. Ketone Bodi Continue reading >>
Ketone Body Utilization For Energy Production And Lipid Synthesis In Isolated Rat Brain Capillaries.
Abstract Isolated brain capillaries from 2-month-old rats were incubated for 2 h in the presence of [3-14C]acetoacetate, D-3-hydroxy[3-14C]butyrate, [U-14C]glucose, [1-14C]acetate or [1-14C]butyrate. Labelled CO2 was collected as an index of oxidative metabolism and incorporation of label precursors into lipids was determined. The rate of CO2 production from glucose was slightly higher than from the other substrates. Interestingly, acetoacetate was oxidized at nearly the same rate as glucose. This shows that ketone bodies could be used as a source of energy by brain capillaries. Radiolabelled substrates were also used for the synthesis of lipids, which was suppressed by the addition of albumin. The incorporation of [U-14C]glucose in total lipids was 10-times higher than that from other precursors. However, glucose labelled almost exclusively the glycerol backbone of phospholipids, especially of phosphatidylcholine. Ketone bodies as well as glucose were incorporated mainly into phospholipids, whereas acetate and butyrate were mainly incorporated into neutral lipids. The contribution to fatty acid synthesis of various substrates was in the following order: butyrate greater than or equal to acetate greater than ketone bodies greater than or equal to glucose. All precursors except glucose were used for sterol synthesis. Glucose produced almost exclusively the glycerol backbone of phospholipids. Continue reading >>
Introductory discusion of fat metabolism, exercise, and fasting. Fatty acids can be used as the major fuel for tissues such as muscle, but they cannot cross the blood-brain barrier, and thus cannot be used by the central nervous system (CNS). This becomes a major problem during starvation (fasting), particularly for organisms such as ourselves in which CNS metabolism constitute a major portion of the resting basal metabolic rate. These organism must provide glucose to the CNS to provide for metabolic needs, and thus during the initial fasting period must break down substantial amounts of muscle tissue (protein) to provide the amino acid precursors of gluconeogenesis. Obviously the organism could not survive long under such a regime. What is needed is an alternate fuel source based on fat rather than muscle. The so-called ketone bodies serve this function: Note that only two of the ketone bodies are in fact ketones, and that acetone is an "unintentional" breakdown product resulting from the instability of acetoacetate at body temperature. Acetone is not available as fuel to any significant extent, and is thus a waste product. CNS tissues can use ketone bodies any time, the problem is the normally very low concentrations (< 0.3 mM) compared to glucose (about 4 mM). Since the KM's for both are similar, the CNS doesn't begin to use ketone bodies in preference to glucose until their concentration exceed's the concentration of glucose in the serum. The system becomes saturated at about 7 mM. The limiting factor in using ketone bodies then becomes the ability of the liver to synthesis them, which requires the induction of the enzymes required for acetoacetate biosynthesis. Normal glucose concentrations inhibit ketone body synthesis, thus the ketone bodies will only begin to be Continue reading >>
What is Ketogenesis? Ketogenesis (1, 2) is a biochemical process that produces ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies the needed energy of certain organs, especially the brain. Not having enough ketogenesis could result to hypoglycaemia and over production of ketone bodies leading to a condition called ketoacidosis. It releases ketones when fat is broken down for energy. There are many ways to release ketones such as through urination and exhaling acetone. Ketones have sweet smell on the breath. (3) Ketogenesis and ketoacidosis are entirely different thing. Ketoacidosis is associated with diabetes and alcoholism, which could lead to even serious condition like kidney failure and even death. Picture 1 : Ketogenic pathway Photo Source : medchrome.com Image 2 : A pyramid of ketogenic diet Photo Source : www.healthline.com What are Ketone bodies? Ketone bodies are water soluble molecules produced by the liver from fatty acids during low food intake or fasting. They are also formed when the body experienced starvation, carbohydrate restrictive diet, and prolonged intense exercises. It is also possible in people with diabetes mellitus type 1. The ketone bodies are picked up by the extra hepatic tissues and will convert to acetyl-CoA. They will enter the citric acid cycle and oxidized in the mitochondria to be used as energy. Ketone bodies are needed by the brain to convert acetyl-coA into long chain fatty acids. Ketone bodies are produced in the absence of glucose. (1, 2, 3) It is easy to detect the presence of ketone bodies. Just observe the person’s breath. The smell of the breath is fruity and sometimes described as a nail polish remover-like. It depicts the presence of acetone or ethyl acetate. The ketone bodies includ Continue reading >>
What is ketosis? Ketosis is the physiological state where the concentration of ketone bodies in the blood is higher than normal. This is generally agreed to be at beta-hydroxybutyrate (BHB) concentrations greater than 0.5 mM. How to achieve ketosis? Ketosis occurs either as a result of increased fat oxidation, whilst fasting or following a strict ketosis diet plan (ENDOGENOUS ketosis), or after consuming a ketone supplement (EXOGENOUS ketosis). When in a state of ketosis the body can use ketones to provide a fuel for cellular respiration instead of its usual substrates: carbohydrate, fat or protein. Why does ketosis exist? Normally, the body breaks down carbohydrates, fat, and (sometimes) proteins to provide energy. When carbohydrate is consumed in the diet, some is used immediately to maintain blood glucose levels, and the rest is stored. The hormone that signals to cells to store carbohydrate is insulin. The liver stores carbohydrate as glycogen, this is broken down and released between meals to keep blood glucose levels constant. Muscles also store glycogen, when broken down this provides fuel for exercise. Most cells in the body can switch readily between using carbohydrates and fat as fuel. Fuel used depends on substrate availability, on the energy demands of the cell and other neural and hormonal signals. The brain is different as it is dependent on carbohydrates as a fuel source. This is because fats cannot easily cross the blood-brain barrier. The inability to make use of energy within fat poses a problem during periods where there is limited carbohydrate in the diet. If blood glucose levels fall to low, brain function declines. Relatively little energy is stored as carbohydrate (2,000 kCal) compared to fat (150,000 kCal). The body's store of carbohydrates runs Continue reading >>
Oncology Letters 14: 673-680, 2017
Abstract. Normal and cancerous cells are suggested to have differential utilization of fatty acids and ketone bodies, which could be exploited in cancer therapy. The present study exam- ined the effect of 3-hydroxybutyric acid (3-HBA), which is a ketone body generating acetyl-CoA, and lauric acid (LAA, C12:0), which is a medium-chain saturated fatty acid trans- located to mitochondria in a carnitine-independent manner to produce acetyl-CoA, on the energy metabolism of mouse CT26 colon cancer cells. In CT26 cells expressing 3-HBA and LAA transporters, 3-HBA and LAA reduced cell prolif- eration, mitochondrial volume and lactate production, and increased oxidative stress, particularly in low-glucose condi- tions. Concurrent treatment with 3-HBA and LAA under glucose starvation had a synergistic effect on cell growth inhibition. In addition, LAA and LAA + 3-HBA promoted an imbalance in the expression of enzymes in the electron transport chain. These findings suggested that treatment with 3-HBA and/or LAA during glucose starvation may reprogram energy metabolism and decrease the proliferation of cancer cells. Introduction The difference in energy production between cancer cells and normal cells is considered to be one of the available targets for the treatment of cancer (1). Unlike normal cells, cancer cells obtain energy mostly via glycolysis, while mitochondrial oxidative phosphorylation is reduced (2). As tumor cells actively proliferate, they require a constant energy supply and it has been postulated that they switch to aerobic glycolysis characterized by rapid ATP production, which is known as the Warburg effect (2). It is hypothesized that the purpose of the Warburg effect is to avoid the excessive generation of reactive oxygen species (ROS) during oxidative phosphory Continue reading >>
Ketosis, Ketones, And How It All Works
Ketosis is a process that the body does on an everyday basis, regardless of the number of carbs you eat. Your body adapts to what is put in it, processing different types of nutrients into the fuels that it needs. Proteins, fats, and carbs can all be processed for use. Eating a low carb, high fat diet just ramps up this process, which is a normal and safe chemical reaction. When you eat carbohydrate based foods or excess amounts of protein, your body will break this down into sugar – known as glucose. Why? Glucose is needed in the creation of ATP (an energy molecule), which is a fuel that is needed for the daily activities and maintenance inside our bodies. If you’ve ever used our keto calculator to determine your caloric needs, you will see that your body uses up quite a lot of calories. It’s true, our bodies use up much of the nutrients we intake just to maintain itself on a daily basis. If you eat enough food, there will likely be an excess of glucose that your body doesn’t need. There are two main things that happen to excess glucose if your body doesn’t need it: Glycogenesis. Excess glucose will be converted to glycogen and stored in your liver and muscles. Estimates show that only about half of your daily energy can be stored as glycogen. Lipogenesis. If there’s already enough glycogen in your muscles and liver, any extra glucose will be converted into fats and stored. So, what happens to you once your body has no more glucose or glycogen? Ketosis happens. When your body has no access to food, like when you are sleeping or when you are on a ketogenic diet, the body will burn fat and create molecules called ketones. We can thank our body’s ability to switch metabolic pathways for that. These ketones are created when the body breaks down fats, creating Continue reading >>
Ketone Bodies In Energy, Neuroprotection, And Possibly In The Effects Of Dietary Restriction
The Durk Pearson & Sandy Shaw® Life Extension NewsTM Volume 6 No. 4 • September 2003 Ketone Bodies in Energy, Neuroprotection, and Possibly in the Effects of Dietary Restriction Ketone bodies, natural metabolites produced from fatty acids, are sources of energy that can be used when there is insulin deficiency (which may be pathological, as in diabetes, or as a result of consuming low dietary carbohydrate) or mitochondrial senescence. Ketone bodies are found in moderate amounts in prolonged human fasting and in type 2 diabetes. Interestingly, ketones are very efficient sources of energy. One paper1 reports that the efficiency of cardiac hydraulic work (in rat hearts) was 10.5% in hearts perfused with glucose alone, and increased to 28% in combination with insulin, to 24% with ketones, and to 36% on addition of the combination. Addition of insulin, ketones, and the combination increased acetyl CoA (in the tricarboxylic acid cycle) 9-fold, 15-fold, and 18-fold, respectively, with corresponding decreases in CoA. “Addition of insulin increased the efficiency of hydraulic work per mole of oxygen consumed in [rat] heart 28% by decreasing oxygen consumption by 14% and increasing cardiac work 13%. Addition of ketones, on the other hand, increased the efficiency mainly by increasing hydraulic work, at the same time decreasing oxygen consumption by only a small percentage.” The authors propose that “The increase in efficiency caused by ketones therefore was compatible with a decrease in proton leakage across mitochondrial membrane due simply to a decrease in potential, as has been previously suggested.” We have written earlier in this newsletter on the hypothesis that increased mitochondrial membrane potential (which increases free radical production in mitochondria) i Continue reading >>
Introduction To Degradation Of Lipids And Ketone Bodies Metabolism
Content: 1. Introduction to degradation of lipids and ketone bodies metabolism 2. Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids 3. Synthesis and utilisation of ketone bodies _ Triacylglycerol (TAG) contain huge amounts of chemical energy. It is very profitable to store energy in TAG because 1 g of water-free TAG stores 5 times more energy than 1 g of hydrated glycogen. Complete oxidation of 1 g of TAG yields 38 kJ, 1g of saccharides or proteins only 17 kJ. Man that weighs 70 kg has 400 000 kJ in his TAG (that weight approximately 10,5 kg). This reserve of energy makes us able to survive starving in weeks. TAG accumulate predominantly in adipocyte cytoplasm. There are more types of fatty acid oxidation. Individual types can be distinguished by different Greek letters. Greek letter denote atom in the fatty acid chain where reactions take place. β-oxidation is of major importance, it is localised in mitochondrial matrix. ω- and α- oxidation are localised in endoplasmic reticulum. Animal cells cannot convert fatty acids to glucose. Gluconeogenesis requires besides other things (1) energy, (2) carbon residues. Fatty acids are rich source of energy but they are not source of carbon residues (there is however one important exception, i.e. odd-numbered fatty acids). This is because cells are not able to convert AcCoA to neither pyruvate, nor OAA. Both carbons are split away as CO2. PDH is irreversible. Plant cells are capable of conversion of AcCoA to OAA in glyoxylate cycle. _ Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids Lipids are used for energy production, this process take place in 3 phases: 1) Lipid mobilisation – hydrolysis of TAG to FA and glycerol. FA and glycerol are transported Continue reading >>
Ketones: Your Brain’s Preferred Fuel Source
Ketones have long been touted as a superior fuel source for the brain that possesses a wide array of cognitive benefits. Our brains are made up of two types of cells, neurons, and glial cells, and both are imperative for our brains to function properly (1). Under normal physiological conditions, the principle energy source utilized by the brain cells is glucose (2). Glucose transporters saturate brain capillaries to allow glucose to cross the blood-brain barrier. Once in the brain, glucose is metabolized to pyruvate which enters the mitochondria of the brain cells to ultimately generate energy through aerobic metabolism (3). However, ketone bodies may also provide energy to the brain through different mechanisms. Brain Fuel In addition to glucose, brain cells can derive energy from monocarboxylates which include lactate and the ketone bodies beta-hydroxybutyrate (β-HB) and acetoacetate (AcAc) (2). It is controversial whether or not lactate can be used as a fuel source in the brain; however, many laboratories have reported that BHB is a major fuel supplier for the brain, especially under specific physiological conditions (3,4). BHB and glucose do not nourish the brain uniformly but rather have specific areas of localization. BHB accumulates primarily in the pituitary and pineal glands, as well as in portions of the hypothalamus, and the lower cortical layers (4). Physiological conditions that elevate BHB and consequently provide increased energy to the aforementioned areas of the brain include starvation, fasting, pregnancy, prolonged exercise, uremia, during the prenatal period, infancy, during the chronic consumption of a high fat/low carbohydrate ketogenic diet, and possibly even ketone supplementation (4). Ketones: Brain’s Utilization Capacity Low circulating gluc Continue reading >>
ketone body any of three related compounds, including acetone, found in the blood and urine when there is excessive oxidation of fatty acids by the liver, as during starvation or pregnancy, or in diabetes ketone body Any of three compounds, acetoacetic acid, acetone, and beta-hydroxybutyric acid, that are ketones or derivatives of ketones and are intermediate products of fatty acid metabolism. Ketone bodies accumulate in the blood and urine when fats are being used for energy instead of carbohydrates, as in individuals affected by starvation or uncontrolled diabetes mellitus. Also called acetone body . THE AMERICAN HERITAGE® DICTIONARY OF THE ENGLISH LANGUAGE, FIFTH EDITION by the Editors of the American Heritage Dictionaries. Copyright © 2016, 2011 by Houghton Mifflin Harcourt Publishing Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved. ketone-body Continue reading >>
The Fat-fueled Brain: Unnatural Or Advantageous?
Disclaimer: First things first. Please note that I am in no way endorsing nutritional ketosis as a supplement to, or a replacement for medication. As you’ll see below, data exploring the potential neuroprotective effects of ketosis are still scarce, and we don’t yet know the side effects of a long-term ketogenic diet. This post talks about the SCIENCE behind ketosis, and is not meant in any way as medical advice. The ketogenic diet is a nutritionist’s nightmare. High in saturated fat and VERY low in carbohydrates, “keto” is adopted by a growing population to paradoxically promote weight loss and mental well-being. Drinking coffee with butter? Eating a block of cream cheese? Little to no fruit? To the uninitiated, keto defies all common sense, inviting skeptics to wave it off as an unnatural “bacon-and-steak” fad diet. Yet versions of the ketogenic diet have been used to successfully treat drug-resistant epilepsy in children since the 1920s – potentially even back in the biblical ages. Emerging evidence from animal models and clinical trials suggest keto may be therapeutically used in many other neurological disorders, including head ache, neurodegenerative diseases, sleep disorders, bipolar disorder, autism and brain cancer. With no apparent side effects. Sound too good to be true? I feel ya! Where are these neuroprotective effects coming from? What’s going on in the brain on a ketogenic diet? Ketosis in a nutshell In essence, a ketogenic diet mimics starvation, allowing the body to go into a metabolic state called ketosis (key-tow-sis). Normally, human bodies are sugar-driven machines: ingested carbohydrates are broken down into glucose, which is mainly transported and used as energy or stored as glycogen in liver and muscle tissue. When deprived of d Continue reading >>
There is a lot of confusion about the term ketosis among medical professionals as well as laypeople. It is important to understand when and why nutritional ketosis occurs, and why it should not be confused with the metabolic disorder we call ketoacidosis. Ketosis is a metabolic state where the liver produces small organic molecules called ketone bodies. Most cells in the body can use ketone bodies as a source of energy. When there is a limited supply of external energy sources, such as during prolonged fasting or carbohydrate restriction, ketone bodies can provide energy for most organs. In this situation, ketosis can be regarded as a reasonable, adaptive physiologic response that is essential for life, enabling us to survive periods of famine. Nutritional ketosis should not be confused with ketoacidosis, a metabolic condition where the blood becomes acidic as a result of the accumulation of ketone bodies. Ketoacidosis can have serious consequences and may need urgent medical treatment. The most common forms are diabetic ketoacidosis and alcoholic ketoacidosis. What Is Ketosis? The human body can be regarded as a biologic machine. Machines need energy to operate. Some use gasoline, others use electricity, and some use other power resources. Glucose is the primary fuel for most cells and organs in the body. To obtain energy, cells must take up glucose from the blood. Once glucose enters the cells, a series of metabolic reactions break it down into carbon dioxide and water, releasing energy in the process. The body has an ability to store excess glucose in the form of glycogen. In this way, energy can be stored for later use. Glycogen consists of long chains of glucose molecules and is primarily found in the liver and skeletal muscle. Liver glycogen stores are used to mai Continue reading >>
Ketone Bodies: A Review Of Physiology, Pathophysiology And Application Of Monitoring To Diabetes.
Abstract Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB:AcAc) rises from normal (1:1) to as high as 10:1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 microl). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies. Continue reading >>
ketone body n. Any of three compounds, acetoacetic acid, acetone, and beta-hydroxybutyric acid, that are ketones or derivatives of ketones and are intermediate products of fatty acid metabolism. Ketone bodies accumulate in the blood and urine when fats are being used for energy instead of carbohydrates, as in individuals affected by starvation or uncontrolled diabetes mellitus. Also called acetone body. American Heritage® Dictionary of the English Language, Fifth Edition. Copyright © 2016 by Houghton Mifflin Harcourt Publishing Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved. ketone body n (Biochemistry) biochem any of three compounds (acetoacetic acid, 3-hydroxybutanoic acid, and acetone) produced when fatty acids are broken down in the liver to provide a source of energy. Excess ketone bodies are present in the blood and urine of people unable to use glucose as an energy source, as in diabetes and starvation. Also called: acetone body Collins English Dictionary – Complete and Unabridged, 12th Edition 2014 © HarperCollins Publishers 1991, 1994, 1998, 2000, 2003, 2006, 2007, 2009, 2011, 2014 ke′tone bod′y n. any of several compounds, as acetoacetic acid, acetone, and hydroxybutyric acid, that are intermediate in the metabolism of fatty acids and are produced in excessive amounts under certain abnormal conditions, as in diabetes mellitus. Random House Kernerman Webster's College Dictionary, © 2010 K Dictionaries Ltd. Copyright 2005, 1997, 1991 by Random House, Inc. All rights reserved. Noun 1. ketone body - a ketone that is an intermediate product of the breakdown of fats in the body; any of three compounds (acetoacetic acid, acetone, and/or beta-hydroxybutyric acid) found in excess in blood and urine of persons with meta Continue reading >>