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How Are Ketones Excreted From The Body

Starvation: Metabolic Changes

Starvation: Metabolic Changes

Abstract Animals, including humans, invoke a comprehensive programme of hormonal and metabolic adaptations that enable them to withstand prolonged periods of starvation. The brain is only capable of using glucose or ketone bodies as respiratory fuel. During prolonged starvation, the primary source of glucose is gluconeogenesis from amino acids arising from muscle proteolysis. To spare glucose use (and thus spare muscle protein) most tissues of the body utilise fat‐derived fuels (fatty acid and ketone bodies). As starvation progresses ketone bodies also become the major fuel of the brain, again reducing the need for glucose. High concentrations of ketone bodies result in significant ketonuria with ketones excreted as ammonium salts. The ammonia is derived from the catabolism of glutamine in the kidney with the carbon skeleton being recovered as glucose. This well‐orchestrated pattern of metabolism allows a consistent fuel supply to the brain and other tissues during prolonged starvation. Key Concepts Circulating glucose concentrations do not drop below 3.5 mmol L−1 even in prolonged starvation. During starvation, the brain must be supplied with fuel in the form of glucose or ketone bodies. Carbohydrate reserves are depleted after 24 h of starvation. In prolonged starvation, gluconeogenesis provides the glucose oxidised by the brain. The major substrates for gluconeogenesis are amino acids derived from skeletal muscle protein breakdown. Circulating ketone body concentrations rise during prolonged starvation. During starvation, most tissues utilise fatty acids and/or ketone bodies to spare glucose for the brain. Glucose utilisation by the brain is decreased during prolonged starvation as the brain utilises ketone bodies as the major fuel. High concentrations of keton Continue reading >>

Ketosis

Ketosis

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 >>

Metabolism And Ketosis

Metabolism And Ketosis

Dr. Eades, If the body tends to resort to gluconeogenesis for glucose during a short-term carbohydrate deficit, are those who inconsistently reduce carb intake only messing things up by not effecting full blown ketosis? If the body will still prefer glucose as main energy source unless forced otherwise for at least a few days, is it absolutely necessary to completely transform metabolism for minimal muscle loss? Also, if alcohol is broken down into ketones and acetaldehyde, technically couldn’t you continue to drink during your diet or would the resulting gluconeogenesis inhibition from alcohol lead to blood glucose problems on top of the ketotic metabolism? Would your liver ever just be overwhelmed by all that action? I’m still in high school so hypothetical, of course haha… Sorry, lots of questions but I’m always so curious. Thank you so much for taking the time to inform the public. You’re my hero! P.S. Random question…what’s the difference between beta and gamma hydroxybutyric acids? It’s crazy how simple orientation can be the difference between a ketone and date rape drug…biochem is so cool! P.P.S. You should definitely post the details of that inner mitochondrial membrane transport. I’m curious how much energy expenditure we’re talkin there.. Keep doin your thing! Your Fan, Trey No, I don’t think people are messing up if they don’t get into full-blown ketosis. For short term low-carb dieting, the body turns to glycogen. Gluconeogenesis kicks in fairly quickly, though, and uses dietary protein – assuming there is plenty – before turning to muscle tissue for glucose substrate. And you have the Cori cycle kicking in and all sorts of things to spare muscle, so I wouldn’t worry about it. And you can continue to drink while low-carbing. Continue reading >>

The Effect Of Ketone Bodies On Renal Ammoniogenesis

The Effect Of Ketone Bodies On Renal Ammoniogenesis

GuYLEMIEUX, PATRICK VINAY, PIRRE ROBITAILLE, GERARDE. PLANTw, YOLANDELUSSIER, and PIEmuE MARTIN From the Renal Laboratory, Hdtel-Dieu Hospital and the Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada A B S T R A C T Infusion of ketone bodies to ammonium chloride-loaded acidotic dogs was found to induce sig- nificant reduction in urinary excretion of ammonia. This effect could not be attributed to urinary pH varia- tions. Total ammonia production by the left kidney was measured in 25 animals infused during 90 min with the sodium salt of D,L-f-hydroxybutyric acid ad- justed to pH 6.0 or 4.2. Ketonemia averaged 4.5 mM/ liter. In all experiments the ammonia content of both urine and renal venous blood fell markedly so that ammoniogenesis was depressed by 60% or more within 60 min after the onset of infusion. Administration of equimolar quantities of sodium -acetoacetate adjusted to pH 6.0 resulted in a 50% decrease in renal ammonia production. Infusion of ketone bodies adjusted to pH 6.0 is usually accompanied by a small increase in extra- cellular bicarbonate (3.7 mM/liter). However infusion of D,L-sodium lactate or sodium bicarbonate in amounts sufficient to induce a similar rise in plasma bicarbonate resulted in only a slight decrement in ammonia pro- duction (15%). The continuous infusion of 5% mannitol alone during 90-150 min failed to influence renal am- moniogenesis. Infusion of pure sodium-free P-hydroxy- butyric acid prepared by ion exchange (pH 2.2) resulted in a 50% decrease in renal ammoniogenesis in spite of the fact that both urinary pH and plasma bicarbonate fell significantly. During all experiments where ketones were infused, the renal extraction of glutamine became This work was presented in part at the 4th Intern Continue reading >>

Norm Of Ketone Bodies During Pregnancy

Norm Of Ketone Bodies During Pregnancy

Ketone bodies during pregnancy are another analysis that must be passed on to a future mother. Ketone bodies are in the urine, and allow you to determine how the pregnancy is, whether there is an infection in the body or everything is in order. Any woman will be useful to know why during pregnancy, so often pass urine tests, and that it can be learned. Let's consider what ketone bodies are, how they affect pregnancy, and what is their norm in the urine of a pregnant woman. Ketone bodies during pregnancy should be kept in small amounts in the urine. As a rule, the allocation of ketoids in knocks from 20 to 50 mg. In the general analysis of urine, these indicators are almost not perceptible. Therefore, every pregnant woman should take special tests to determine this indicator. The increased value of ketone bodies in urine is considered pathology, that is ketonuria. Ketone bodies during pregnancy are manifested in the event that in the female body there is an infection also, they can talk about early toxicosis. Ketone bodies poison the body of a pregnant woman with acetone, this complicates the process of bearing a baby. Jumps ketone bodies can be observed with a sharp decrease in the weight of the pregnant woman, but this is observed in the first months of pregnancy, during the period of toxicosis. Sometimes ketone bodies indicate that the pregnant woman has problems with the liver, as well as with the digestive system because of an incorrect, unbalanced diet. Continue reading >>

Understanding Ketones And Low-carbohydrate Diets

Understanding Ketones And Low-carbohydrate Diets

A common misunderstanding regarding the metabolic effects of low-carbohydrate diets concerns the formation of ketone bodies. The presence of ketones caused by fat burning is often confused with ketoacidosis resulting from uncontrolled diabetes, starvation or certain alcoholic conditions. Dietary ketones are more common than most people realize. As well as being caused by low-carbohydrate eating, they will occur as a result of any weight-loss plan when fat is burned or even after an overnight fast. Ketones and Evolution Ketones are produced when fat is utilized to meet energy needs. This happens when the diet comprises less than approximately 50 grams of carbohydrates per day. Ketones are a source of energy for the heart muscle and a backup fuel source for the brain. It is because of our bodies’ ability to utilize stored fat in times of a limited food supply that the human species has survived. This ability to safely use ketones preserves lean body mass while providing fuel for the brain. Ketoacidosis or Dietary Ketones Diabetic ketoacidosis occurs when blood glucose levels are exceedingly high because insulin levels are too low. The inability of the body to handle such high levels of glucose leads to a large production of acid compounds that the body is unable to neutralize. Dehydration occurs as the body loses large amounts of water through the urine attempting to remove excess glucose. This combination of circumstances leads to a life-threatening acidosis. To clear up the misconception and confusion common among many people (including the medical profession), one does not get acidosis simply by having ketones from controlling carbs. Note that one can be burning fat without excreting ketones in the urine. The excess ketones not used for energy are excreted. I think t Continue reading >>

Ketone Bodies Metabolism

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 >>

Why I Stopped Testing My Ketones On A Ketogenic Diet

Why I Stopped Testing My Ketones On A Ketogenic Diet

On measuring Ketones. Like many people, when I first started a Ketogenic diet in early 2014 I bought the Ketostix and just couldn’t wait to see the color change. And change it did! It was neat, and it provided motivation for me to continue. Eventually, I got a blood meter, a breath meter and spent lots of time (and money) testing ketones. Between a Ketonix Breath Ketone Analyzer, as well as dozens of blood ketone test strips, I’ve probably spent well over $500 testing ketones. The main thing I learned from my extensive ketone testing regimen is that the results vary widely and there’s little application to my goals. Eventually, I stopped testing and here are several reasons why: 1. Burning fatty acids from fat is the main benefit of a ketogenic diet On a ketogenic diet, some of the brain’s energetic demand is fueled by ketones, but the heart, muscles, etc. are fueled by fatty acids. Most of the energy we utilize both at rest and at sub-maximal exertion on a ketogenic diet is fatty acid, not ketones. Quoting Dr. Ron Rosedale on chasing ketones at the Keto Summit: “I don’t want people to have the mindset that it’s the ketones that are the benefit of the diet. They are a beneficial side effect, but the main benefit is that you are burning fatty acids from fat. The more fatty acids from fat you are burning, the less glucose you need to burn. And that’s really where you are getting the benefit…So ketones are great but the term ketogenic diet indicating that the diet is so good because you are generating all these ketones is a misinterpretation of the benefit. The main benefit is that you are burning fatty acids, and as a side effect of burning fatty acids you are producing ketones that your body can burn too!” 2. Urine Ketones aka “peetones” are ridic Continue reading >>

The Natureof Diabetic Acidosis

The Natureof Diabetic Acidosis

(From the Department of Internal Medicine of Yale University and the Medical Service of the New Haven Hospital, New Haven) Since the discovery that ketone acids are produced in the body and accumulate in the blood to excess in severe diabetes, general opinion has held that the accumulation of these chemical compounds is responsible for the syndrome known as diabetic coma. The general application of the term acidosis to the condition is in itself sufficient evidence of the importance which is attached to this disorder of metabolism. Difference of opinion seems to have been restricted chiefly to the question of the relative parts played by the ketone bodies as such and by the reduction of blood alkali and diminution of pH which they caused. In favor of direct action of the ketones have been cited the demonstrated anesthetic effects of acetone and diacetic acid, while the adherents of the acidosis theory depend upon experiments in which various workers, beginning with Walter (1)'have demonstrated the disastrous, even lethal, effects of injections of massive doses of mineral acids. With the appearance and application of accurate and practical methods for the determination of blood bicarbonate and pH it has be- come increasingly apparent that alkali deficits of the magnitude found in diabetic acidosis, when they are produced experimentally or occur in the course of other diseases, are not necessarliy attended by a syndrome resembling that of diabetic acidosis. This has, perhaps, given more weight to the arguments of those who would hold that acetone and di- acetic acid, by their anesthetic and poisonous effects, are responsible for the symptoms and fatalities. On the other hand there is but the scan- tiest positive quantitative evidence to support such a theory. The an- esth Continue reading >>

Ketone Bodies

Ketone Bodies

Also found in: Dictionary, Thesaurus, Legal, Financial, Encyclopedia, Wikipedia. Related to ketone bodies: ketosis ketone [ke´tōn] any compound containing the carbonyl group, C=O, and having hydrocarbon groups attached to the carbonyl carbon, i.e., the carbonyl group is within a chain of carbon atoms. ketone bodies the substances acetone, acetoacetic acid, and β-hydroxybutyric acid; except for acetone (which may arise spontaneously from acetoacetic acid), they are normal metabolic products of lipid and pyruvate within the liver, and are oxidized by muscles. Excessive production leads to urinary excretion of these bodies, as in diabetes mellitus; see also ketosis. Called also acetone bodies. Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved. ketone bodies two products of lipid pyruvate metabolism, beta-hydroxybutyric acid and aminoacetic acid, from which acetone may arise spontaneously. Ketone bodies are produced from acetyl-CoA in the liver and are oxidized by the muscles. Excessive production leads to their excretion in urine, as in diabetes mellitus. Also called acetone bodies. Ketones, Blood and Urine Synonym/acronym: Ketone bodies, acetoacetate, acetone. Common use To investigate diabetes as the cause of ketoacidosis and monitor therapeutic interventions. Specimen Serum (1 mL) collected from gold-, red-, or red/gray-top tube. Urine (5 mL), random or timed specimen, collected in a clean plastic collection container. Normal findings (Method: Colorimetric nitroprusside reaction) Negative. Description Ketone bodies refer to the three intermediate products of metabolism: acetone, acetoacetic acid, and β-hydroxybutyrate. Even though β-hydroxybutyrate Continue reading >>

Understanding Ketone Bodies And The Role Of Raspberry Ketones

Understanding Ketone Bodies And The Role Of Raspberry Ketones

Before we delve into what raspberry ketones are, and how they work, we feel it is important to understand that ketones aren’t exclusive to red raspberries. Ketone bodies are actually a naturally occurring compound in our body. What Are Ketones? Ketone bodies are the metabolic end products of our body’s fatty acid metabolism. The liver breaks down fatty acids in our body as a way to provide us energy when blood-glucose levels are low. Ketone bodies are the by-products of this process. They become available to the body as an alternative energy source. Ketones are naturally occurring in our body, going all the way back to birth. Ketone bodies are essentially three water-soluble compounds. The liver transports two of these, acetoacetate and beta-hydroxybutyrate, to other tissues where they can be reconverted to acetyl-CoA to supply energy. The third compound, acetone, cannot be reconverted to acetyl-CoA. It is instead excreted in urine or exhaled while breathing. The Body And Energy It is commonly known that glucose (sugar), just like ketones, are another source of fuel and energy within the body. The carbohydrates that we consume in our diet ensure that glucose is present in our bloodstream. This is the first place your body will turn to when looking for fuel. The problem is the human body does not store glucose very well without consistent replenishment. This isn’t a problem for most people, since we as a nation tend to consume an unhealthy amount of sugars and carbohydrates, and don’t burn them off with sufficient exercise. In cases where glucose is less available, for instance if we engage in strenuous exercise, or we are fasting, or trying out a low-carbohydrate diet, most tissues turn to fatty acids for an additional energy source. However the human brain cann Continue reading >>

Utilization Of Ketone Bodies, Regulation And Clinical Significance Of Ketogenesis

Utilization Of Ketone Bodies, Regulation And Clinical Significance Of Ketogenesis

Ketone bodies are utilized by extra hepatic tissues via a series of cytosolic reactions that are essentially a reversal of ketone body synthesis; the ketones must be reconverted to acetyl Co A in the mitochondria (figure-1) Steps 1) Utilization of β-Hydroxy Butyrate Beta-hydroxybutyrate is first oxidized to acetoacetate with the production of one NADH (Figure-1, step-1). In tissues actively utilizing ketones for energy production, NAD+/NADH ratio is always higher so as to drive the β-hydroxybutyrate dehydrogenase catalyzed reaction in the direction of acetoacetate synthesis. Biological significance D (-)-3-Hydroxybutyrate is oxidized to produce acetoacetate as well as NADH for use in oxidative phosphorylation. D (-)-3-Hydroxybutyrate is the main ketone body excreted in urine. 2) Utilization of Acetoacetate a) Coenzyme A must be added to the acetoacetate. The thioester bond is a high energy bond, so ATP equivalents must be used. In this case the energy comes from a trans esterification of the CoASH from succinyl CoA to acetoacetate by Coenzyme A transferase (Figure-1, step-2), also called Succinyl co A: Acetoacetate co A transferase, also known as Thiophorase. The Succinyl CoA comes from the TCA cycle. This reaction bypasses the Succinyl-CoA synthetase step of the TCA cycle; hence there is no GTP formation at this step although it does not alter the amount of carbon in the cycle. Biological significance The liver has acetoacetate available to supply to other organs because it lacks this particular CoA transferase and that is the reason “Ketone bodies are synthesized in the liver but utilized in the peripheral tissues”. The latter enzyme is present at high levels in most tissues except the liver. Importantly, very low-level of enzyme expression in the liver allows t Continue reading >>

Ketones

Ketones

Excess ketones are dangerous for someone with diabetes... Low insulin, combined with relatively normal glucagon and epinephrine levels, causes fat to be released from fat cells, which then turns into ketones. Excess formation of ketones is dangerous and is a medical emergency In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketones can develop. What are ketones and why do I need to know about them? Ketones and ketoacids are alternative fuels for the body that are made when glucose is in short supply. They are made in the liver from the breakdown of fats. Ketones are formed when there is not enough sugar or glucose to supply the body’s fuel needs. This occurs overnight, and during dieting or fasting. During these periods, insulin levels are low, but glucagon and epinephrine levels are relatively normal. This combination of low insulin, and relatively normal glucagon and epinephrine levels causes fat to be released from the fat cells. The fats travel through the blood circulation to reach the liver where they are processed into ketone units. The ketone units then circulate back into the blood stream and are picked up by the muscle and other tissues to fuel your body’s metabolism. In a person without diabetes, ketone production is the body’s normal adaptation to starvation. Blood sugar levels never get too high, because the production is regulated by just the right balance of insulin, glucagon and other hormones. However, in an individual with diabetes, dangerous and life-threatening levels of ketone Continue reading >>

Ketosis & Measuring Ketones

Ketosis & Measuring Ketones

Generally, ketone concentrations are lower in the morning and higher in the evening. Whatever time you pick to measure ketone levels, make sure to keep it consistent. Also, do not measure your ketone levels right after exercise. Ketone levels tend to be lower while your glucose levels higher so you won't get representative numbers. Keep in mind there are daily fluctuations caused by changes in hormone levels. Don't get discouraged! Another aspect that affects the level of ketones is the amount of fat in your diet. Some of you may show higher concentration of ketones after a high-fat meal. Coconut oil contains MCTs that will help you boost ketones. To easily increase your fat intake on a ketogenic diet, try fat bombs - snacks with at least 80% fat content. Ketone levels tend to be higher after extensive aerobic exercise as your body depletes glycogen stores. Exercise may help you get into ketosis faster. ketogenic "fruity" breath is not pleasant for most people. To avoid this, drink a lot of water, mint tea and make sure you eat foods rich in electrolytes. Avoid too many chewing gums and mints, as it may put you out of ketosis; there may be hidden carbs affecting your blood sugar. Increase your electrolyte intake, especially potassium. You are likely going to lose some sodium and potassium when switching to the keto diet. Finally, if you find it hard to lose weight on a ketogenic diet, there may be plenty other reasons than the level of ketone bodies: Not Losing Weight on Low-Carb Ketogenic Diet? Don’t Give Up and Read Further. Continue reading >>

Ketone Bodies

Ketone Bodies

The term “ketone bodies” refers primarily to two compounds: acetoacetate and β‐hydroxy‐butyrate, which are formed from acetyl‐CoA when the supply of TCA‐cycle intermediates is low, such as in periods of prolonged fasting. They can substitute for glucose in skeletal muscle, and, to some extent, in the brain. The first step in ketone body formation is the condensation of two molecules of acetyl‐CoA in a reverse of the thiolase reaction. The product, acetoacetyl‐CoA, accepts another acetyl group from acetyl‐CoA to form β‐hydroxy‐β‐hydroxymethylglutaryl‐CoA (HMG‐CoA). HMG‐CoA has several purposes: It serves as the initial compound for cholesterol synthesis or it can be cleaved to acetoacetate and acetyl‐CoA. Acetoacetate can be reduced to β‐hydroxybutyrate or can be exported directly to the bloodstream. Acetoacetate and β‐hydroxybutyrate circulate in the blood to provide energy to the tissues. Acetoacetate can also spontaneously decarboxylate to form acetone: Although acetone is a very minor product of normal metabolism, diabetics whose disease is not well‐managed often have high levels of ketone bodies in their circulation. The acetone that is formed from decarboxylation of acetoacetate is excreted through the lungs, causing characteristic “acetone breath.” Continue reading >>

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