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How Are Ketones Produced In The Body?

Ketone Bodies

Ketone Bodies

Abstract Ketone bodies are water‐soluble equivalents of fatty acids. They can substitute for glucose in peripheral tissues, especially in the brain, when glucose becomes limited in physiological and pathological states. Recent findings demonstrate that they also act as signalling metabolites, thus participating in the organism adaptation to the environment, such as during fasting, calorie restriction or prolonged exercise. Diabetes is the most common pathological cause of elevated blood ketone bodies. Ketone bodies are produced in excess in response to low insulin levels and high levels of counterregulatory hormones, the result being the development of metabolic acidosis that is associated with serious health complications. Yet, ketogenic diets have been used for decades to increase ketone body synthesis for their neuroprotective properties as central signalling metabolites and as main energy‐providing substrate for the brain, in epilepsy and neurodegenerative diseases. Key Concepts Ketone bodies are key energy substrates and signalling molecules Ketone bodies participate in energy homeostasis Diabetic ketoacidosis is the most common pathological cause of elevated blood ketone bodies and is associated with serious health complications Ketone bodies are neuroprotective Ketone bodies offer promising perspectives in clinical therapy for certain metabolic diseases, neurodegenerative diseases and cancers Keywords: ketone bodies; energy homeostasis; starvation; exercise; ketoacidosis; neuroprotection Continue reading >>

Is Ketosis Dangerous?

Is Ketosis Dangerous?

Duck Dodgers October 14, 2014 Peter, An article by Per Wikholm was published in this month’s LCHF Magasinet, where Per demonstrates that the Inuit could not have been in ketosis given that the scientific literature is abundantly clear, over and over again, that the Inuit consumed too much protein, and more importantly, Per debunks Stefansson’s claims for high fat with writing from his own books—Stef admitted in the pemmican recipes that Arctic caribou was too lean to make pemmican that supported ketosis. The most popular LCHF bloggers in Sweden, Andreas Eenfeldt/Diet Doctor and Annika Dahlquist have reluctantly agreed with Per’s findings—admitting that the Inuit were likely not ketogenic from their diet. I’ve put together a comprehensive review of the scientific literature regarding the Inuit, encompassing over two dozen studies, spanning 150 years, with references from explorers, including Stefansson. In the comments section of that post, Per gives a brief overview of how he was able to prove Stefansson’s observations on high fat intake were flawed. The post is a review of all the available literature that I could find (over two dozen studies). But, the literature certainly does not in any way support ketosis from the Inuit diet due to such high protein consumption. As Per (and Stefansson) points out, the caribou is too lean and as the many quotes show, the Inuit were saving their blubber and fat for the long dark Winter to power their oil lamps and heat their igloos. Again and again, we see that in the literature, as even Stefansson admits this. As far as glycogen is concerned, their glycogen intake is probably not worth scrutinizing given the well-documented high protein consumption in every published study. It really is besides the point. But, interest Continue reading >>

Exogenous Ketones: What They Are, Benefits Of Use And How They Work

Exogenous Ketones: What They Are, Benefits Of Use And How They Work

Exogenous ketones have become a popular nutritional supplement since their introduction in 2014. Like with any new supplement, though, there tends to be a lot of misinformation that you have to sift your way through to find the reliable data. So, this article does the hard work for you and gets right to what the true benefits and drawbacks of exogenous ketones are. We also cover what forms of ketones to consider, how they function in the body, and their role in future research. What Are Ketones? Our bodies use ketones via our mitochondria to generate energy. They are an alternative fuel source to glucose. Ketones are simple compounds because of their small molecular structure and weight. Specifically, they are organic (carbon-based) compounds that contain a central carbon atom double-bonded to an oxygen atom and two carbon-containing substituents, denoted by “R” (see chemical structure below). In humans, there are 3 different ketones produced by the mitochondria of the liver. These are also often referred to as ketone bodies. The three ketones are: Acetone Acetoacetic Acid Beta-Hydroxybutyric Acid (also known Beta Hydroxybuyrate or BHB). Other chemical names include 3-hydroxybutyric acid or 3-hydroxybutyrate. BHB is not technically a ketone since it contains a reactive OH-group in place of where a double-bonded oxygen normally would be as you can see in the diagram below. Yet, BHB still functions like a ketone in the body and converts into energy much like acetoacetate and acetone. This happens via the acetoacetate and acetyl-CoA pathway. Note that acetone conversion to acetyl-CoA is not efficient due to the need to convert acetone to acetoacetate via decarboxylation. However, BHB still functions like a ketone in the body and can be converted to energy (via acetoace Continue reading >>

Ketone Ester Effects On Metabolism And Transcription

Ketone Ester Effects On Metabolism And Transcription

Abstract Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free fatty acids. The elevation of ketone bodies increases the energy of ATP hydrolysis by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple, thus increasing the redox span between site I and site II. In contrast, metabolism of fatty acids leads to a reduction of both mitochondrial NAD and mitochondrial coenzyme Q causing a decrease in the ΔG of ATP hydrolysis. In contrast, feeding ketone body esters leads to pure ketosis, unaccompanied by elevation of free fatty acids, producing a physiological state not previously seen in nature. The effects of pure ketosis on transcription and upon certain neurodegenerative diseases make approach not only interesting, but of potential therapeutic value. PRODUCTION OF KETONE BODIES Ketone bodies are formed in the liver from free fatty acids released from adipose tissue. As the blood concentration of free fatty acids increases, concentration of blood ketone bodies is correspondingly increased (1, 2). Ketone bodies serve as a physiological respiratory substrate and are the physiological response to prolonged starvation in man (3, 4), where the blood level of ketones reaches 5–7 mM (5). If the release of free fatty acids from adipose tissue exceeds the capacity of tissue to metabolize them, as occurs during insulin deficiency of type I diabetes or less commonly in the insulin resistance of type II diabetes, severe and potentially fatal diabetic ketoacidosis can occur, where blood ketone body levels can reach 20 mM or higher (2) resulting in a decrease in blood bicarbonate to almost 0 mM and blood pH to 6.9. Diabetic ketoacidosis, which is a Continue reading >>

What Is Acetone?

What Is Acetone?

You can find it in paint thinners, nail polish, and the manufacturing of plastics. But it’s also found naturally (and safely) in the human body, especially in those following a ketogenic diet. What we’re talking about here is acetone, a ketone body produced in the ketosis process, which has many benefits in the body. But what is acetone, exactly? What role does it play in ketosis? Those are questions we’ll be diving into below so you can better understand how this molecule fits into your ketogenic diet and why it’s important. What is Acetone? Acetone is a type of ketone. When someone is eating a high-fat and low-carb diet (namely, the ketogenic diet) or goes through prolonged fasting and there isn’t enough glucose in the body for fuel, the liver starts breaking down fatty acids for energy for the body and the brain. This is the process known as ketosis, the primary function and goal of the ketogenic diet. When ketosis happens, water-soluble molecules called ketone bodies, or just simply “ketones,” are released. These three ketones are: Acetoacetate Beta-hydroxybutyrate Acetone Acetoacetate is created first, followed by beta-hydroxybutyrate and acetone. Acetone is created spontaneously from the breakdown of acetoacetate and is the simplest and most volatile ketone. It diffuses into the lungs and exits the body from exhaled breath. Acetone Benefits on the Ketogenic Diet One way that those on a keto diet ensure they maintain their ketosis, and receive the benefits of ketosis, is by measuring the amount of acetone on the breath. Typically, the higher amount of acetone present, the further they are into ketosis. Weight Loss Benefits There are many reasons someone might choose to follow a keto diet and put their body in ketosis. Benefits of being in ketosis incl Continue reading >>

Ketosis

Ketosis

Idiots' Guide to The Biochemistry and Management of Ketosis Ketosis is a disease of dry cows that shows up in fresh cows. Fundamentally, we have a situation where the cow is mobilizing body fat (condition) faster than the liver is able to metabolize it. In order for the liver to normally metabolize that fat, glucose is required. If glucose availability is limited due to inadequate substrate (mostly propionate from the diet) or glucose production via gluconeogenesis is inadequate or impaired, then ketosis can result because of the inability to convert the fat to energy. Loss/mobilization of body fat is a normal part of the onset of lactation. As the rate of fat mobilization rises, circulating NEFA levels begin to rise. If these fatty acids reach the liver and begin to accumulate in significant amounts, the liver switches away from TCA towards ketogenesis in an attempt to provide more energy and eliminate the fat buildup. Ketogenesis produces the ketone bodies, acetoacetate and beta-hydroxybutyrate. Some ketone production is normal in all periparturient cows, so diagnosis is made on clinical history, physical examination, and the presence of significant ketones in milk or urine. Presence of ketones in milk or urine is inadequate, in and or itself, to make the diagnosis of clinical ketosis. Feed intake, or lack thereof, is a critical component in the onset of ketosis. In all cows, dry matter intake begins to decline approximately one month prior to calving, although many people will not notice this decline until several days prior to calving. as feed intake declines and galactopoeisis begins, body fats are mobilized, resulting in an increase in circulationg NEFA levels. NEFAs themselves are mild appetite suppressants, so they continue to hamper feed intake. NEFAs are also Continue reading >>

Beta Hydroxybutyrate

Beta Hydroxybutyrate

Summary Beta hydroxybutyrate (BHB) is the first ketone body produced in a fasting state. It is commonly produced by the body during periods without much food (glucose) in order to provide an alternative energy fuel source [1]. Although it is not technically a “ketone” (owing to the bonding structure), for the purposes of this post it is. Diets that are low in carbohydrates and high in fatty acids can either prompt the body to produce ketone bodies, such as beta hydroxybutyrate, or allow people to consume them exogenously (outside the body) instead. These exogenous ketone supplements have grown in popularity along with the ketogenic diet and media attention from popular icons such as Tim Ferriss [2] and Dave Asprey [3]. Although supplementation of beta hydroxybutyrate has been described as “jet fuel” [4] and undesirable, modern iterations of exogenous ketones are making it easier for anyone to utilize these ketone bodies for optimal brain performance. Also Known As Ketone bodies, Beta-hydroxybutyric acid, 3-hydroxybutyrate Editors’ Thoughts on Beta Hydroxybutyrate Making exogenous ketones palatable is one of the most exciting things for me right now. As I prepare to embark on an experiment doing cyclical ketosis with my girlfriend, exogenous ketone bodies like beta hydroxybutyrate will be incredibly important for kickstarting ketosis (for her especially). The addition of beta hydroxybutyrate will make the ketogenic process easier, though I’m not sure how much. Mansal Denton, Nootropedia Editor Benefits of Beta Hydroxybutyrate There are a host of benefits of beta hydroxybutyrate, but it is primarily known as a fuel source in the absence of glucose. Within 24 – 72 hours without food, the body no longer uses glucose as the main fuel support system, which is wh Continue reading >>

Ketone Bodies (urine)

Ketone Bodies (urine)

Does this test have other names? Ketone test, urine ketones What is this test? This test is used to check the level of ketones in your urine. Normally, your body burns sugar for energy. But if you have diabetes, you may not have enough insulin for the sugar in your bloodstream to be used for fuel. When this happens, your body burns fat instead and produces substances called ketones. The ketones end up in your blood and urine. It's normal to have a small amount of ketones in your body. But high ketone levels could result in serious illness or death. Checking for ketones keeps this from happening. Why do I need this test? You may need this test if you have a high level of blood sugar. People with high levels of blood sugar often have high ketone levels. If you have high blood sugar levels and type 1 or type 2 diabetes, it's important to check your ketone levels. People without diabetes can also have ketones in the urine if their body is using fat for fuel instead of glucose. This can happen with chronic vomiting, extreme exercise, low-carbohydrate diets, or eating disorders. Checking your ketones is especially important if you have diabetes and: Your blood sugar goes above 300 mg/dL You abuse alcohol You have diarrhea You stop eating carbohydrates like rice and bread You're pregnant You've been fasting You've been vomiting You have an infection Your healthcare provider may order this test, or have you test yourself, if you: Urinate frequently Are often quite thirsty or tired Have muscle aches Have shortness of breath or trouble breathing Have nausea or vomiting Are confused Have a fruity smell to your breath What other tests might I have along with this test? Your healthcare provider may also check for ketones in your blood if you have high levels of ketones in your urine 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 >>

Ketone Bodies Metabolic Pathway (pw:0000069)

Ketone Bodies Metabolic Pathway (pw:0000069)

Description The ketone bodies metabolic pathway is used to convert acetyl-CoA formed in the liver into "ketone bodies": acetone, and more importantly acetoacetate and 3-hydroxybutyrate, which are transported in the blood to extrahepatic tissues where they are converted to acetyl-CoA and oxidized via the citrate cycle pathway for energy. The brain, which usually uses glucose for energy, can utilize ketone bodies under starvation conditions, when glucose is not available. When acetyl-CoA is not being metaboli...(more) Description: ENCODES a protein that exhibits 3-hydroxybutyrate dehydrogenase activity (ortholog); NAD binding (ortholog); oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor (ortholog); INVOLVED IN epithelial cell differentiation (ortholog); fatty acid beta-oxidation (ortholog); heme metabolic process (ortholog); PARTICIPATES IN butanoate metabolic pathway; ketone bodies metabolic pathway; FOUND IN cytoplasm (ortholog); cytosol (ortholog); extracellular exosome (ortholog); INTERACTS WITH 2,3,7,8-tetrachlorodibenzodioxine; 2,4-dinitrotoluene; 2,6-dinitrotoluene Continue reading >>

Blood Ketones

Blood Ketones

On This Site Tests: Urine Ketones (see Urinalysis - The Chemical Exam); Blood Gases; Glucose Tests Elsewhere On The Web Ask a Laboratory Scientist Your questions will be answered by a laboratory scientist as part of a voluntary service provided by one of our partners, the American Society for Clinical Laboratory Science (ASCLS). Click on the Contact a Scientist button below to be re-directed to the ASCLS site to complete a request form. If your question relates to this web site and not to a specific lab test, please submit it via our Contact Us page instead. Thank you. 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 >>

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 >>

Regulation Of Ketone Body And Coenzyme A

Regulation Of Ketone Body And Coenzyme A

METABOLISM IN LIVER by SHUANG DENG Submitted in partial fulfillment of the requirements For the Degree of Doctor of Philosophy Dissertation Adviser: Henri Brunengraber, M.D., Ph.D. Department of Nutrition CASE WESTERN RESERVE UNIVERSITY August, 2011 SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of __________________ ____________ _ _ candidate for the ________________________________degree *. (signed) ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. Shuang Deng (chair of the committee) Edith Lerner, PhD Colleen Croniger, PhD Henri Brunengraber, MD, PhD Doctor of Philosophy Janos Kerner, PhD Michelle Puchowicz, PhD Paul Ernsberger, PhD I dedicate this work to my parents, my son and my husband iv TABLE OF CONTENTS Table of Contents…………………………………………………………………. iv List of Tables………………………………………………………………………. viii List of Figures……………………………………………………………………… ix Acknowledgements………………â Continue reading >>

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