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Why Are Ketones Produced?

Ketone Bodies: A Review Of Physiology, Pathophysiology And Application Of Monitoring To Diabetes.

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 >>

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 >>

What Are Ketone Bodies And Why Are They In The Body?

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 >>

Urine Tests For Diabetes: Glucose Levels And Ketones

Urine Tests For Diabetes: Glucose Levels And Ketones

The human body primarily runs on glucose. When your body is low on glucose, or if you have diabetes and don’t have enough insulin to help your cells absorb the glucose, your body starts breaking down fats for energy. Ketones (chemically known as ketone bodies) are byproducts of the breakdown of fatty acids. The breakdown of fat for fuel and the creation of ketones is a normal process for everyone. In a person without diabetes, insulin, glucagon, and other hormones prevent ketone levels in the blood from getting too high. However, people with diabetes are at risk for ketone buildup in their blood. If left untreated, people with type 1 diabetes are at risk for developing a condition called diabetic ketoacidosis (DKA). While rare, it’s possible for people with type 2 diabetes to experience DKA in certain circumstances as well. If you have diabetes, you need to be especially aware of the symptoms that having too many ketones in your body can cause. These include: If you don’t get treatment, the symptoms can progress to: a fruity breath odor stomach pain trouble breathing You should always seek immediate medical attention if your ketone levels are high. Testing your blood or urine to measure your ketone levels can all be done at home. At-home testing kits are available for both types of tests, although urine testing continues to be more common. Urine tests are available without a prescription at most drugstores, or you can buy them online. You should test your urine or blood for ketones when any of the following occurs: Your blood sugar is higher than 240 mg/dL. You feel sick or nauseated, regardless of your blood sugar reading. To perform a urine test, you urinate into a clean container and dip the test strip into the urine. For a child who isn’t potty-trained, a pa Continue reading >>

Ketone Bodies Formed In The Liver Are Exported To Other Organs

Ketone Bodies Formed In The Liver Are Exported To Other Organs

Ketone Bodies In human beings and most other mammals, acetyl-CoA formed in the liver during oxidation of fatty acids may enter the citric acid cycle (stage 2 of Fig. 16-7) or it may be converted to the "ketone bodies" acetoacetate, D-β-hydroxybutyrate, and acetone for export to other tissues. (The term "bodies" is a historical artifact; these compounds are soluble in blood and urine.) Acetone, produced in smaller quantities than the other ketone bodies, is exhaled. Acetoacetate and D-β-hydroxybutyrate are transported by the blood to the extrahepatic tissues, where they are oxidized via the citric acid cycle to provide much of the energy required by tissues such as skeletal and heart muscle and the renal cortex. The brain, which normally prefers glucose as a fuel, can adapt to the use of acetoacetate or D-β-hydroxybutyrate under starvation conditions, when glucose is unavailable. A major determinant of the pathway taken by acetyl-CoA in liver mitochondria is the availability of oxaloacetate to initiate entry of acetyl-CoA into the citric acid cycle. Under some circumstances (such as starvation) oxaloacetate is drawn out of the citric acid cycle for use in synthesizing glucose. When the oxaloacetate concentration is very low, little acetyl-CoA enters the cycle, and ketone body formation is favored. The production and export of ketone bodies from the liver to extrahepatic tissues allows continued oxidation of fatty acids in the liver when acetyl-CoA is not being oxidized via the citric acid cycle. Overproduction of ketone bodies can occur in conditions of severe starvation and in uncontrolled diabetes. The first step in formation of acetoacetate in the liver (Fig. 16-16) is the enzymatic condensation of two molecules of acetyl-CoA, catalyzed by thiolase; this is simply Continue reading >>

Ketone Body Metabolism

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 >>

Getting To Know Ketones

Getting To Know Ketones

People with diabetes, particularly those with Type 1 diabetes, have been at least vaguely aware of the word ketones for a long time. With the recent resurgence of popular interest in low-carbohydrate diets, however, just about everyone seems to be talking about ketones these days. But does anyone really know what ketones are? Are they a danger to your health (as in diabetic ketoacidosis), or a sign that you have lowered your carbohydrate intake enough to cause weight loss (as some people who follow low-carbohydrate diets believe)? What are ketones? Ketones are end-products of fat metabolism in the body. That is, they are formed when fat is burned for energy by the muscles. Chemically, they are acids known as ketone bodies, and there are three types: beta-hydroxybutyric acid, aceto-acetic acid, and acetone. But you don’t have to be a chemist to understand what role they play in the body. To get to know ketones, it’s helpful to understand how your body burns fuel. A simple analogy is that of an automobile. For a car engine to run, the engine must burn fuel (gasoline), and when the fuel is burned, exhaust (carbon monoxide) is created. The carbon monoxide is the end-product of gasoline combustion. Your body also has an engine that must burn fuel to operate. The engine is muscle, and the fuel is fat, carbohydrate (glucose), and, in certain conditions, protein. When fat is burned, the “exhaust” is ketones, and when glucose is burned, the “exhaust” is lactic acid. Fat is more desirable as a fuel than glucose because there are more calories in a gram of fat (9 calories per gram) than there are in a gram of glucose (4 calories per gram), so you get more energy per gram of fat burned. In a sense, you could call fat a high-test fuel. But there is one catch to burning f Continue reading >>

Your Brain On Ketones

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 >>

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 >>

Ketone Bodies

Ketone Bodies

Overview Structure two types acetoacetate β-hydroxybutyrate β-hydroxybutyrate + NAD+ → acetoacetate + NADH ↑ NADH:NAD+ ratio results in ↑ β-hydroxybutyrate:acetoacetate ratio 1 ketone body = 2 acetyl-CoA Function produced by the liver brain can use ketones if glucose supplies fall >1 week of fasting can provide energy to body in prolonged energy needs prolonged starvation glycogen and gluconeogenic substrates are exhausted can provide energy if citric acid cycle unable to function diabetic ketoacidosis cycle component (oxaloacetate) consumed for gluconeogenesis alcoholism ethanol dehydrogenase consumes NAD+ (converts to NADH) ↑ NADH:NAD+ ratio in liver favors use of oxaloacetate for ketogenesis rather than gluconeogenesis. RBCs cannot use ketones as they lack mitochondria Synthesis occurs in hepatocyte mitochondria liver cannot use ketones as energy lacks β-ketoacyl-CoA transferase (thiophorase) which converts acetoacetate to acetoacetyl under normal conditions acetoacetate = β-hydroxybutyrate HMG CoA synthase is rate limiting enzyme Clinical relevance ketoacidosis pathogenesis ↑ ketone levels caused by poorly controlled type I diabetes mellitus liver ketone production exceeds ketone consumption in periphery possible in type II diabetes mellitus but rare alcoholism chronic hypoglycemia results in ↑ ketone production presentation β-hydroxybutyrate > acetoacetate due to ↑ NADH:NAD+ ratio acetone gives breath a fruity odor polyuria ↑ thirst tests ↓ plasma HCO3 hypokalemia individuals are initially hyperkalemic (lack of insulin + acidosis) because K leaves the cells overall though the total body K is depleted replete K in these patients once the hyperkalemia begins to correct nitroprusside urine test for ketones may not be strongly + does not detect 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 >>

Ketosis, Ketones, And How It All Works

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 Body Production And Disposal In Diabetic Ketosis: A Comparison With Fasting Ketosis

Ketone Body Production And Disposal In Diabetic Ketosis: A Comparison With Fasting Ketosis

This work compares the metabolism of total ketone bodies in 13 insulin-deprived, type I diabetic subjects and 26 control subjects fasted for 15 h to 23 days, with the two groups showing a similar range of ketone body levels (1–12 mM). Ketone turnover rate was measured using a primed, constant infusion of either 14C-acetoacetate or 14C-β-hydroxybutyrate, both tracers yielding comparable results. The major conclusions of this study are the following: the kinetics of ketone bodies are comparable in the two groups within the range of concentrations tested. The hyperketonemia of fasting and diabetes is primarily caused by an increased production of ketone bodies, but the phenomenon is amplified by a progressive limitation in the ability of tissues to remove ketones from blood as the concentration rises. The inverse relationship between the metabolic clearance and the plasma levels of ketones, which underlies this process, represents a general characteristic of ketone body metabolism that applies to both types of ketosis. A maximal metabolic disposal rate of about 2.3 mmol/min/1.73 m2 is attained in both groups at concentrations of 10–12 mM, which correspond to the highest ketone body levels encountered during prolonged fasting. Thus, up to these levels, there is no evidence for the existence of a ketone body removal defect specific to diabetes. Continue reading >>

Ketone Bodies

Ketone Bodies

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[1] during periods of low food intake (fasting), carbohydrate restrictive diets, starvation, prolonged intense exercise,[2], 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.[3] 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).[1] 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)[1]. 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 >>

6 Health Benefits Of Ketogenesis And Ketone Bodies

6 Health Benefits Of Ketogenesis And Ketone Bodies

With heavy coverage in the media, ketogenic diets are all the rage right now. And for a good reason; for some people, they truly work. But what do all these different terms like ketogenesis and ketone bodies actually mean? Firstly, this article takes a look at what the ketogenesis pathway is and what ketone bodies do. Following this, it will examine six potential health benefits of ketones and nutritional ketosis. What is Ketogenesis? Ketogenesis is a biochemical process through which the body breaks down fatty acids into ketone bodies (we’ll come to those in a minute). Synthesis of ketone bodies through ketogenesis kicks in during times of carbohydrate restriction or periods of fasting. When carbohydrate is in short supply, ketones become the default energy source for our body. As a result, a diet to induce ketogenesis should ideally restrict carb intake to a maximum of around 50 grams per day (1, 2). Ketogenesis may also occur at slightly higher levels of carbohydrate intake, but for the full benefits, it is better to aim lower. When ketogenesis takes place, the body produces ketone bodies as an alternative fuel to glucose. This physiological state is known as ‘nutritional ketosis’ – the primary objective of ketogenic diets. There are various methods you can use to test if you are “in ketosis”. Key Point: Ketogenesis is a biological pathway that breaks fats down into a form of energy called ketone bodies. What Are Ketone Bodies? Ketone bodies are water-soluble compounds that act as a form of energy in the body. There are three major types of ketone body; Acetoacetate Beta-hydroxybutyrate Acetone (a compound created through the breakdown of acetoacetate) The first thing to remember is that these ketones satisfy our body’s energy requirements in the same w Continue reading >>

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