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 Body Metabolism
Ketone body metabolism includes ketone body synthesis (ketogenesis) and breakdown (ketolysis). When the body goes from the fed to the fasted state the liver switches from an organ of carbohydrate utilization and fatty acid synthesis to one of fatty acid oxidation and ketone body production. This metabolic switch is amplified in uncontrolled diabetes. In these states the fat-derived energy (ketone bodies) generated in the liver enter the blood stream and are used by other organs, such as the brain, heart, kidney cortex and skeletal muscle. Ketone bodies are particularly important for the brain which has no other substantial non-glucose-derived energy source. The two main ketone bodies are acetoacetate (AcAc) and 3-hydroxybutyrate (3HB) also referred to as β-hydroxybutyrate, with acetone the third, and least abundant. Ketone bodies are always present in the blood and their levels increase during fasting and prolonged exercise. After an over-night fast, ketone bodies supply 2–6% of the body's energy requirements, while they supply 30–40% of the energy needs after a 3-day fast. When they build up in the blood they spill over into the urine. The presence of elevated ketone bodies in the blood is termed ketosis and the presence of ketone bodies in the urine is called ketonuria. The body can also rid itself of acetone through the lungs which gives the breath a fruity odour. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis, high levels of ketone bodies are produced in response to low insulin levels and high levels of counter-regulatory hormones. Ketone bodies The term ‘ketone bodies’ refers to three molecules, acetoacetate (AcAc), 3-hydroxybutyrate (3HB) and acetone (Figure 1). 3HB is formed from the reduction of AcAc i Continue reading >>
What Are Ketones?
With the gradual resurgence of low-carb diets in recent years, the word “ketones” is thrown around a lot. But many people aren’t really aware of the details. What are ketones, really? And what do they do in the body? There can be a lot of misinformation regarding the answers to these questions, so read on for a full overview of ketones and their role in a ketogenic diet. Ketones, also known as “ketone bodies,” are byproducts of the body breaking down fat for energy that occurs when carbohydrate intake is low. Here’s how it works: When there isn’t a sufficient level of available glucose — which is what the body uses for its main source of fuel — and glycogen levels are depleted, blood sugar and insulin are lowered and the body looks for an alternative source of fuel: in this case, fat. This process can happen when a person fasting, after prolonged exercise, during starvation, or when eating a low-carb, ketogenic diet. And when the body begins breaking down fats for energy like this, a process known as beta-oxidation, ketones are formed for use as fuel for the body and brain. This is known as ketosis. People following a ketogenic diet specifically reduce their carbohydrate intake for this reason: to create ketones for energy. Many people use the benefits of ketosis — less reliance on carbs and more burning of fat — to possibly help lower blood pressure, reduce cravings, improve cholesterol, increase weight loss, improve energy, and more. TYPES OF KETONE BODIES So, what else about ketones do we need to know? To start, there are technically three types of ketone bodies: Acetoacetate (AcAc) Beta-hydroxybutyric acid (BHB) Acetone Both acetoacetate and beta-hydroxybutyrate are responsible for transporting energy from the liver to other tissues in the body Continue reading >>
Brain: Ketone Metabolism
Definition The three ketone bodies are acetone, acetoacetic acid, and beta-hydroxybutyric acid. Ketone bodies are derived from the incomplete oxidation of fatty acids in the liver and are used for energy (ATP generation) in the heart and brain. Ketone bodies are transported from the liver to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce energy, via the Krebs cycle. The brain gets its energy from ketone bodies when insufficient glucose is available, such as during fasting and starvation. In the event of low blood glucose, most other tissues have additional energy sources besides ketone bodies (such as fatty acids), but the brain does not. After the diet has been changed to lower blood glucose for 3 days, the brain gets 30% of its energy from ketone bodies. After about 40 days, this goes up to 70% (during the initial stages the brain does not burn ketones, since they are an important substrate for lipid synthesis in the brain). By using alternative fuels, the demand for glucose is reduced and muscle proteins are spared further degradation. Subspecialty Keyword history See Also: Sources PubMed 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 >>
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 >>
Ketone Bodies Metabolism
1. Metabolism of ketone bodies Gandham.Rajeev Email:[email protected] 2. • Carbohydrates are essential for the metabolism of fat or FAT is burned under the fire of carbohydrates. • Acetyl CoA formed from fatty acids can enter & get oxidized in TCA cycle only when carbohydrates are available. • During starvation & diabetes mellitus, acetyl CoA takes the alternate route of formation of ketone bodies. 3. • Acetone, acetoacetate & β-hydroxybutyrate (or 3-hydroxybutyrate) are known as ketone bodies • β-hydroxybutyrate does not possess a keto (C=O) group. • Acetone & acetoacetate are true ketone bodies. • Ketone bodies are water-soluble & energy yielding. • Acetone, it cannot be metabolized 4. CH3 – C – CH3 O Acetone CH3 – C – CH2 – COO- O Acetoacetate CH3 – CH – CH2 – COO- OH I β-Hydroxybutyrate 5. • Acetoacetate is the primary ketone body. • β-hydroxybutyrate & acetone are secondary ketone bodies. • Site: • Synthesized exclusively by the liver mitochondria. • The enzymes are located in mitochondrial matrix. • Precursor: • Acetyl CoA, formed by oxidation of fatty acids, pyruvate or some amino acids 6. • Ketone body biosynthesis occurs in 5 steps as follows. 1. Condensation: • Two molecules of acetyl CoA are condensed to form acetoacetyl CoA. • This reaction is catalyzed by thiolase, an enzyme involved in the final step of β- oxidation. 7. • Acetoacetate synthesis is appropriately regarded as the reversal of thiolase reaction of fatty acid oxidation. 2. Production of HMG CoA: • Acetoacetyl CoA combines with another molecule of acetyl CoA to produce β-hydroxy β-methyl glutaryl CoA (HMC CoA). • This reaction is catalyzed by the enzyme HMG CoA synthase. 8. • Mitochondrial HMG CoA is used for ketogenesis. 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 >>
Your Brain On Ketones
The modern prescription of high carbohydrate, low fat diets and eating snacks between meals has coincided with an increase in obesity, diabetes, and and increase in the incidence of many mental health disorders, including depression, anxiety, and eating disorders. In addition, many of these disorders are striking the population at younger ages. While most people would agree that diet has a lot to do with the development of obesity and diabetes, many would disagree that what we eat has much to do with our mental health and outlook. I believe that what we eat has a lot to do with the health of our brains, though of course mental illness (like physical illness) has multifactorial causes, and by no means should we diminish the importance of addressing all the causes in each individual. But let's examine the opposite of the modern high carbohydrate, low fat, constant snacking lifestyle and how that might affect the brain. The opposite of a low fat, snacking lifestyle would be the lifestyle our ancestors lived for tens of thousands of generations, the lifestyle for which our brains are primarily evolved. It seems reasonable that we would have had extended periods without food, either because there was none available, or we were busy doing something else. Then we would follow that period with a filling meal of gathered plant and animal products, preferentially selecting the fat. During the day we might have eaten a piece of fruit, or greens, or a grub we dug up, but anything filling or high in calories (such as a starchy tuber) would have to be killed, butchered, and/or carefully prepared before eating. Fortunately, we have a terrific system of fuel for periods of fasting or low carbohydrate eating, our body (and brain) can readily shift from burning glucose to burning what ar 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 >>
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 >>
Ketone bodies Acetone Acetoacetic acid (R)-beta-Hydroxybutyric acid Ketone bodies are three water-soluble molecules (acetoacetate, beta-hydroxybutyrate, and their spontaneous breakdown product, acetone) that are produced by the liver from fatty acids during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,, alcoholism or in untreated (or inadequately treated) type 1 diabetes mellitus. These ketone bodies are readily picked up by the extra-hepatic tissues, and converted into acetyl-CoA which then enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are also used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above (i.e. fasting, starving, low carbohydrate diets, prolonged exercise and untreated type 1 diabetes mellitus) as a result of intense gluconeogenesis, which is the production of glucose from non-carbohydrate sources (not including fatty acids). They are therefore always released into the blood by the liver together with newly produced glucose, after the liver glycogen stores have been depleted (these glycogen stores are depleted after only 24 hours of fasting). When two acetyl-CoA molecules lose their -CoAs, (or Co-enzyme A groups) they can form a (covalent) dimer called acetoacetate. Beta-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol (or hydroxyl) group (see illustration on the right). Both are 4-carbon molecules, that can readily be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted 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 >>
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 >>
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 >>