Understanding Ketosis
To gain a better understanding of ketosis and the ketogenic diet, it is important to take a look at the physiology behind the diet. If you recall from the article What is a Ketogenic Diet? the goal of a ketogenic diet is to induce ketosis by increasing ketone body production. A key step in understanding the diet is to learn what ketosis is, what are ketones and what do they do. “Normal” Metabolism Learning the basics of the various metabolic processes of the body will better your ability to understand ketosis. Under the normal physiological conditions that are common today, glucose is our body’s primary source of energy. Following ingestion, carbohydrates are broken down into glucose and released into the blood stream. This results in the release of insulin from the pancreas. Insulin not only inhibits fat oxidation but also acts as a key holder for cells by allowing glucose from the blood to be shuttled into cells via glucose transporters (GLUT). The amount of insulin required for this action varies between individuals depending on their insulin sensitivity. Once inside the cell, glucose undergoes glycolysis, a metabolic process that produces pyruvate and energy in the form of adenosine triphosphate (ATP). Once pyruvate is formed as an end product of glycolysis, it is shuttled into the mitochondria, where it is converted to acetyl-CoA by pyruvate dehydrogenase. Acetyl-CoA then enters the TCA cycle to produce additional energy with the aid of the electron transport chain. Since glucose is so rapidly metabolized for energy production and has a limited storage capacity, other energy substrates, such as fat, get stored as triglycerides due to our body’s virtually infinite fat storage capacity. When a sufficient source of carbohydrates is not available, the body adap Continue reading >>
Regulation Of Hypothalamic Neuronal Sensing And Food Intake By Ketone Bodies And Fatty Acids
Metabolic sensing neurons in the ventromedial hypothalamus (VMH) alter their activity when ambient levels of metabolic substrates, such as glucose and fatty acids (FA), change. To assess the relationship between a high-fat diet (HFD; 60%) intake on feeding and serum and VMH FA levels, rats were trained to eat a low-fat diet (LFD; 13.5%) or an HFD in 3 h/day and were monitored with VMH FA microdialysis. Despite having higher serum levels, HFD rats had lower VMH FA levels but ate less from 3 to 6 h of refeeding than did LFD rats. However, VMH β-hydroxybutyrate (β-OHB) and VMH-to-serum β-OHB ratio levels were higher in HFD rats during the first 1 h of refeeding, suggesting that VMH astrocyte ketone production mediated their reduced intake. In fact, using calcium imaging in dissociated VMH neurons showed that ketone bodies overrode normal FA sensing, primarily by exciting neurons that were activated or inhibited by oleic acid. Importantly, bilateral inhibition of VMH ketone production with a 3-hydroxy-3-methylglutaryl-CoA synthase inhibitor reversed the 3- to 6-h HFD-induced inhibition of intake but had no effect in LFD-fed rats. These data suggest that a restricted HFD intake regimen inhibits caloric intake as a consequence of FA-induced VMH ketone body production by astrocytes. Several lines of evidence support the idea that food intake can be altered by ingestion of a high-fat diet (HFD) (1–5). Prolonged intraventricular infusion of the long-chain fatty acid (LCFA), oleic acid (OA), causes a decrease in intake (6). However, the physiological significance of such effects on feeding can be questioned, as can those of direct infusions of fatty acid (FA) into brain areas such as the hypothalamus (7). A major problem is that there is no current information about how brai Continue reading >>
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 >>
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 You Should Know About Ketones
When the body cannot obtain energy from food sources of carbohydrates such as bread, potatoes, rice, noodles, cereal, etc., due to the lack of available insulin, the body is starved for energy and starts breaking down fat as an energy source. A by-product of fat breakdown is ketone production, which is toxic to the body. This complication is known as diabetic ketoacidosis (DKA) and can lead to illness or even death. Ketones are produced mainly by type 1 diabetics (children and adults), insulin pump users who may stop getting their insulin for some reason, as well as pregnant women who have gestational, type 1 or type 2 diabetes. Although more rare, people with type 2 diabetes can also produce ketones when they are ill, have an acute trauma incident, or have an infection. During illness, the body is under a great deal of stress and produces extra hormones like adrenaline. Adrenaline helps fight off the infection, but this works against insulin, which then leads to ketone production. Ketones accumulate in the blood and can be recognized in the blood about 2-4 hours prior to appearing in urine. This makes a blood test more accurate than a urine test to detect ketone levels. Time is very important in diagnosing ketoacidosis. There are multiple urine ketone testing strips on the market, but a new meter called the Nova Max Plus has the ability to test glucose as well as ketones in one meter. Here is how it works: The meter will alert you to test for ketones when the glucose reading is over 250mg/dl. A blood drop is taken only from your finger tips (not an alternate site) and used with a special ketone strip, which is green (the blue strip is used for glucose testing). The meter will indicate KET to let you know you are testing for ketones. The strip must be used within 2 minu Continue reading >>
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 >>
Ketones To The Rescue Fashioning Therapies From An Adaptation To Starvation
Ben Harder In times of plenty, both the mind and the body thrive. But deprived of basic sustenance, the mind perishes before the body does. That's not New Age philosophy; it's basic metabolic chemistry. While most of the body manages food shortages with relative ease, the tissues of the brain are vulnerable during periods of scarcity. So when blood sugar dips, the brain must fall back on special biochemistry to meet its energy needs. From studying that metabolic back-up system, a coterie of scientists has drawn inspiration that could lead to a new treatment for conditions as diverse as epilepsy, diabetes, Alzheimer's disease, and heart failure. Most of the time, the body makes its fundamental fuel, glucose, from ingested carbohydrates. With each meal, the bloodstream gets replenished with glucose to replace the blood sugar that hungry cells have consumed to satisfy their metabolic needs. The body can't store glucose well, yet cells must be fed continually. So the body puts away extra energy in the form of fat, which it can break down into energy-supplying fatty acids when needed. A starving animal or a person with normal fat stores can thus sustain most of the body's cells for weeks or months without eating. But brain cells, even hungry ones, can't avail themselves of these emergency stores. A physiological barrier that blocks toxins in the bloodstream so they can't enter the delicate brain also keeps out fat and fatty acids. As a consequence, when glucose in the blood runs low, brain cells can run into trouble. People are uniquely vulnerable to such glucose starvation because of their disproportionate braininess. Although the brain makes up about 2 percent of a normal adult's weight, it commands roughly 20 percent of the body's resting metabolic budget. A condition fou Continue reading >>
Fenofibrate Induces Ketone Body Production In Melanoma And Glioblastoma Cells
1Department of Food Biotechnology, Faculty of Food Technology, University of Agriculture, Krakow, Poland 2Molecular and Metabolic Oncology Program, Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA 3Department of Human Nutrition, Faculty of Food Technology, University of Agriculture, Krakow, Poland 4Neurological Cancer Research, Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA Ketone bodies [beta-hydroxybutyrate (bHB) and acetoacetate] are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly, its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator-activated receptor alpha (PPARa) agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of non-transformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and downregulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma. Continue reading >>
Everything You Need To Know About Ketones
Ketone is an organic compound that the body produces when fats are broken down for energy. People with diabetes may not be able to regulate the level of ketones in their blood, so ketone testing is an essential part of managing their condition. There are three types of ketone, which are collectively known as ketone bodies, or ketones. In this article, we explain when to check for ketones, the types of tests available, and how to understand the results. Contents of this article: What are ketones? The body uses a range of nutrients for energy, including carbohydrates, fats, and proteins. It will use carbohydrates first, but if none are available, the body will burn fat for energy. When this happens, ketones are produced. Ketones have gained attention in recent years due to the popularity of ketogenic diets, in which people eat a low carbohydrate diet so that their body will burn fat instead of carbohydrates. There is currently a lack of clear evidence on the benefits of this diet, and there may be some risks, such as high acidity in the blood and loss of muscle. Typically, carbohydrates are broken down into different nutrients, including blood sugar (glucose), by an enzyme called amylase that occurs naturally in the body. Insulin then transports the sugar to cells to be used for energy. A person with diabetes does not produce enough insulin to transport the blood sugar, or the cells in their body may not accept it properly, which stops the body from using the blood sugar for energy. When sugar can't be used by the cells for energy, the body will start to break down fats for energy instead. Types of ketone and DKA Three types of ketones are always present in the blood: acetoacetate (AcAc) 3-β-hydroxybutyrate (3HB) acetone The levels of each of these ketone bodies will var Continue reading >>
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 >>
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 >>
Ketone Body Formation
Ketone body formation occurs as an alternative energy source during times of prolonged stress e.g. starvation. It occurs in the liver from an initial substrate of: long chain fatty acids; the fatty acids undergo beta-oxidation by their normal pathway within mitochondria until acetyl-CoA is produced, or ketogenic amino acids; amino acids such as leucine and lysine, released at times of energy depletion, are interconverted only to acetyl-CoA Then, three molecules of acetyl-CoA are effectively joined together in three enzyme steps sequentially catalyzed by: acetyl CoA acetyltransferase HMG-CoA transferase HMG-CoA lyase Coenzyme A is regenerated and the ketone body acetoacetate is formed. Finally, acetoacetate is reduced to another ketone body, D-3-hydroxybutyrate, in a reaction catalyzed by 3-hydroxybutyrate dehydrogenase. This requires NADH. The oxidate state of the liver is such that the forward reaction is generally favoured; this results in more hydroxybutyrate being formed than acetoacetate. Continue reading >>
Ketone Bodies As A Fuel For The Brain During Starvation
THE STATUS OF OUR KNOWLEDGE OF STARVATION AND BRAIN METABOLISM IN HUMANS WHEN I BEGAN MY RESEARCH This story begins in the early 1960s when the general level of knowledge about whole-body metabolism during human starvation was grossly deficient. This was partly caused by a lack of accurate and specific methods for measuring hormones and fuels in biological fluids, which became available about 1965.11 Rigidly designed protocols for studying human volunteers or obese patients, who underwent semi- or total starvation for prolonged periods of time, were not widely employed, and much of the published data regarding metabolic events during starvation were not readily accessible. To complicate matters further, a great deal of the available data was confusing because much of the supposition regarding mechanisms used by the body to survive prolonged periods of starvation was based upon information that was obtained from nonstandardized and often erroneous procedures for studying metabolism. For example, the rate of urinary nitrogen excretion during starvation was sometimes confounded by the consumption of carbohydrate during the studies. Today, students of biochemistry take for granted the fact that tissues of the human body have a hierarchy of fuel usage. They know that the brain, an organ devoted to using glucose, can switch to use ketone bodies during prolonged starvation (2–3 days), thus sparing glucose for other tissues (i.e. red blood cells must use glucose as a fuel; without mitochondria, they have no choice!). However, this fundamental insight into human metabolism was not recognized in the early 1960s, when my research in this area began. How this simple but fundamental fact that ketone bodies provide critical fuels for the brain was discovered and its implication for Continue reading >>
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 >>
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 >>
