Ketone Bodies In Energy, Neuroprotection, And Possibly In The Effects Of Dietary Restriction
The Durk Pearson & Sandy Shaw® Life Extension NewsTM Volume 6 No. 4 • September 2003 Ketone Bodies in Energy, Neuroprotection, and Possibly in the Effects of Dietary Restriction Ketone bodies, natural metabolites produced from fatty acids, are sources of energy that can be used when there is insulin deficiency (which may be pathological, as in diabetes, or as a result of consuming low dietary carbohydrate) or mitochondrial senescence. Ketone bodies are found in moderate amounts in prolonged human fasting and in type 2 diabetes. Interestingly, ketones are very efficient sources of energy. One paper1 reports that the efficiency of cardiac hydraulic work (in rat hearts) was 10.5% in hearts perfused with glucose alone, and increased to 28% in combination with insulin, to 24% with ketones, and to 36% on addition of the combination. Addition of insulin, ketones, and the combination increased acetyl CoA (in the tricarboxylic acid cycle) 9-fold, 15-fold, and 18-fold, respectively, with corresponding decreases in CoA. “Addition of insulin increased the efficiency of hydraulic work per mole of oxygen consumed in [rat] heart 28% by decreasing oxygen consumption by 14% and increasing cardiac work 13%. Addition of ketones, on the other hand, increased the efficiency mainly by increasing hydraulic work, at the same time decreasing oxygen consumption by only a small percentage.” The authors propose that “The increase in efficiency caused by ketones therefore was compatible with a decrease in proton leakage across mitochondrial membrane due simply to a decrease in potential, as has been previously suggested.” We have written earlier in this newsletter on the hypothesis that increased mitochondrial membrane potential (which increases free radical production in mitochondria) i Continue reading >>
Introduction To Degradation Of Lipids And Ketone Bodies Metabolism
Content: 1. Introduction to degradation of lipids and ketone bodies metabolism 2. Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids 3. Synthesis and utilisation of ketone bodies _ Triacylglycerol (TAG) contain huge amounts of chemical energy. It is very profitable to store energy in TAG because 1 g of water-free TAG stores 5 times more energy than 1 g of hydrated glycogen. Complete oxidation of 1 g of TAG yields 38 kJ, 1g of saccharides or proteins only 17 kJ. Man that weighs 70 kg has 400 000 kJ in his TAG (that weight approximately 10,5 kg). This reserve of energy makes us able to survive starving in weeks. TAG accumulate predominantly in adipocyte cytoplasm. There are more types of fatty acid oxidation. Individual types can be distinguished by different Greek letters. Greek letter denote atom in the fatty acid chain where reactions take place. β-oxidation is of major importance, it is localised in mitochondrial matrix. ω- and α- oxidation are localised in endoplasmic reticulum. Animal cells cannot convert fatty acids to glucose. Gluconeogenesis requires besides other things (1) energy, (2) carbon residues. Fatty acids are rich source of energy but they are not source of carbon residues (there is however one important exception, i.e. odd-numbered fatty acids). This is because cells are not able to convert AcCoA to neither pyruvate, nor OAA. Both carbons are split away as CO2. PDH is irreversible. Plant cells are capable of conversion of AcCoA to OAA in glyoxylate cycle. _ Lipids as source of energy – degradation of TAG in cells, β-oxidation of fatty acids Lipids are used for energy production, this process take place in 3 phases: 1) Lipid mobilisation – hydrolysis of TAG to FA and glycerol. FA and glycerol are transported Continue reading >>
Benefits Of Fueling Your Body With Ketones
Why Ketones are a better fuel source than glucose Where do our bodies get the energy to fuel our activities of daily living? Glucose is the main fuel source of our bodies, but there is another type of fuel that is available to our bodies, ketones. Ketones are a natural by-product of fat metabolism. When the body has run out of glucose to use as fuel it will switch fuel sources and start converting fat into fatty acids and then into ketones. Our bodies were designed to use this duel source of energy based on how we lived in the caveman days. In the summer and spring when food was plentiful, cavemen would eat more food and pack on the extra and store it as fat. Then in the fall and winter when food was scarce, the cavemen would live off that extra stored fat. Nowadays, since food supply is plentiful all year around and there is no physiological need or demand to live off the stored fat, thus we may just keep packing it on, all year around. What are the differences between ketones and glucose as a source of energy? Research suggests that ketones are a better, cleaner source of energy for the body and actually provide more energy than glucose. Unlike glucose, ketones do not depend on insulin to get into the cells for use. Ketones produce less carbon dioxide and free radicals than when the body uses glucose as a fuel source thus are less toxic for our body, making it a cleaner fuel source. Unfortunately, ketones are harder energy source for our bodies to tap into since they require your body to be in either a starvation mode or at least be in a state of very low in carbohydrates. Nowadays, the most common way of getting the body to produce ketones, or be in a state of ketosis, is by being on a very low carb diet i.e. a ketogenic diet. Typically, a ketogenic diet consists of Continue reading >>
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 >>
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 >>
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 >>
Ketone Bodies Provide An Alternative Fuel Source For Neurons1
Ketone bodies are the brain’s natural back-up fuel2 When glucose levels are low, for example during periods of starvation or from a ketogenic diet, the liver is triggered to produce ketone bodies as a back-up fuel source.2 In adults, significantly elevated ketone body levels are usually encountered only when insulin signaling is disrupted (eg, in diabetes). Therefore, ketosis is often viewed as an abnormal condition. However, ketosis serves as an important survival function during mammalian development and when food is scarce.3 Properties of ketone bodies Ketone body metabolism may have a number of advantages over glucose metabolism: Is able to readily cross blood-brain barrier1 Improves metabolic efficiency4 Reduces production of reactive oxygen species4 Increases antioxidant capacity4 May assist brain cells in clearing away debris from disease or injury3 Can supply up to 60% of the brain’s energy needs2 Metabolism of glucose and ketone bodies in neuronal mitochondria4 Ketone bodies do not undergo glycolysis and are able to enter the TCA cycle in fewer steps than glucose. Acetyl CoA, acetyl coenzyme A; ATP, adenosine triphosphate; TCA cycle, tricarboxylic acid cycle (also known as the citric acid cycle or Krebs cycle). Elevating ketone body levels has a long clinical history5 1970 Modifications made to ketogenic diet to include medium-chain triglycerides. All variations approximately equal in reducing seizures7,8 2004 Phase IIa trial demonstrates correlation between ketosis and improved Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS–Cog) scores in APOE4(-) patients with mild to moderate Alzheimer’s disease11 2009 Medium-chain triglycerides (MCTs) as a source of ketone bodies2 MCTs contain medium-chain fatty acids (octanoic [8:0] and decanoic Continue reading >>
Bcii: Ketone Bodies
Sort The major site of formation of acetoacetate from fatty acids is the: a. adipose tissue. b. intestinal mucosa. c. kidney. d. liver. e. muscle. d. liver. Ketone bodies are formed in the liver and transported to the extrahepatic tissues mainly as: a. acetoacetyl-CoA. b. acetone. c. beta-hydroxybutyric acid. d. beta-hydroxybutyryl-CoA. e. lactic acid. b. acetone. Continue reading >>
Oncology Letters 14: 673-680, 2017
Abstract. Normal and cancerous cells are suggested to have differential utilization of fatty acids and ketone bodies, which could be exploited in cancer therapy. The present study exam- ined the effect of 3-hydroxybutyric acid (3-HBA), which is a ketone body generating acetyl-CoA, and lauric acid (LAA, C12:0), which is a medium-chain saturated fatty acid trans- located to mitochondria in a carnitine-independent manner to produce acetyl-CoA, on the energy metabolism of mouse CT26 colon cancer cells. In CT26 cells expressing 3-HBA and LAA transporters, 3-HBA and LAA reduced cell prolif- eration, mitochondrial volume and lactate production, and increased oxidative stress, particularly in low-glucose condi- tions. Concurrent treatment with 3-HBA and LAA under glucose starvation had a synergistic effect on cell growth inhibition. In addition, LAA and LAA + 3-HBA promoted an imbalance in the expression of enzymes in the electron transport chain. These findings suggested that treatment with 3-HBA and/or LAA during glucose starvation may reprogram energy metabolism and decrease the proliferation of cancer cells. Introduction The difference in energy production between cancer cells and normal cells is considered to be one of the available targets for the treatment of cancer (1). Unlike normal cells, cancer cells obtain energy mostly via glycolysis, while mitochondrial oxidative phosphorylation is reduced (2). As tumor cells actively proliferate, they require a constant energy supply and it has been postulated that they switch to aerobic glycolysis characterized by rapid ATP production, which is known as the Warburg effect (2). It is hypothesized that the purpose of the Warburg effect is to avoid the excessive generation of reactive oxygen species (ROS) during oxidative phosphory Continue reading >>
Question: During Ketogenesis, The Liver Synthesizes Ketone Bodies That Can Be Used As An Energy Source. Put...
During ketogenesis, the liver synthesizes ketone bodies that can be used as an energy source. Put the following statements regarding ketogenesis in the correct order, beginning with a stimulus for ketogenesis. Continue reading >>
Ketone Body Utilization For Energy Production And Lipid Synthesis In Isolated Rat Brain Capillaries.
Abstract Isolated brain capillaries from 2-month-old rats were incubated for 2 h in the presence of [3-14C]acetoacetate, D-3-hydroxy[3-14C]butyrate, [U-14C]glucose, [1-14C]acetate or [1-14C]butyrate. Labelled CO2 was collected as an index of oxidative metabolism and incorporation of label precursors into lipids was determined. The rate of CO2 production from glucose was slightly higher than from the other substrates. Interestingly, acetoacetate was oxidized at nearly the same rate as glucose. This shows that ketone bodies could be used as a source of energy by brain capillaries. Radiolabelled substrates were also used for the synthesis of lipids, which was suppressed by the addition of albumin. The incorporation of [U-14C]glucose in total lipids was 10-times higher than that from other precursors. However, glucose labelled almost exclusively the glycerol backbone of phospholipids, especially of phosphatidylcholine. Ketone bodies as well as glucose were incorporated mainly into phospholipids, whereas acetate and butyrate were mainly incorporated into neutral lipids. The contribution to fatty acid synthesis of various substrates was in the following order: butyrate greater than or equal to acetate greater than ketone bodies greater than or equal to glucose. All precursors except glucose were used for sterol synthesis. Glucose produced almost exclusively the glycerol backbone of phospholipids. Continue reading >>
The Fat-fueled Brain: Unnatural Or Advantageous?
Disclaimer: First things first. Please note that I am in no way endorsing nutritional ketosis as a supplement to, or a replacement for medication. As you’ll see below, data exploring the potential neuroprotective effects of ketosis are still scarce, and we don’t yet know the side effects of a long-term ketogenic diet. This post talks about the SCIENCE behind ketosis, and is not meant in any way as medical advice. The ketogenic diet is a nutritionist’s nightmare. High in saturated fat and VERY low in carbohydrates, “keto” is adopted by a growing population to paradoxically promote weight loss and mental well-being. Drinking coffee with butter? Eating a block of cream cheese? Little to no fruit? To the uninitiated, keto defies all common sense, inviting skeptics to wave it off as an unnatural “bacon-and-steak” fad diet. Yet versions of the ketogenic diet have been used to successfully treat drug-resistant epilepsy in children since the 1920s – potentially even back in the biblical ages. Emerging evidence from animal models and clinical trials suggest keto may be therapeutically used in many other neurological disorders, including head ache, neurodegenerative diseases, sleep disorders, bipolar disorder, autism and brain cancer. With no apparent side effects. Sound too good to be true? I feel ya! Where are these neuroprotective effects coming from? What’s going on in the brain on a ketogenic diet? Ketosis in a nutshell In essence, a ketogenic diet mimics starvation, allowing the body to go into a metabolic state called ketosis (key-tow-sis). Normally, human bodies are sugar-driven machines: ingested carbohydrates are broken down into glucose, which is mainly transported and used as energy or stored as glycogen in liver and muscle tissue. When deprived of d Continue reading >>
Ketone Bodies 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 >>
Introductory discusion of fat metabolism, exercise, and fasting. Fatty acids can be used as the major fuel for tissues such as muscle, but they cannot cross the blood-brain barrier, and thus cannot be used by the central nervous system (CNS). This becomes a major problem during starvation (fasting), particularly for organisms such as ourselves in which CNS metabolism constitute a major portion of the resting basal metabolic rate. These organism must provide glucose to the CNS to provide for metabolic needs, and thus during the initial fasting period must break down substantial amounts of muscle tissue (protein) to provide the amino acid precursors of gluconeogenesis. Obviously the organism could not survive long under such a regime. What is needed is an alternate fuel source based on fat rather than muscle. The so-called ketone bodies serve this function: Note that only two of the ketone bodies are in fact ketones, and that acetone is an "unintentional" breakdown product resulting from the instability of acetoacetate at body temperature. Acetone is not available as fuel to any significant extent, and is thus a waste product. CNS tissues can use ketone bodies any time, the problem is the normally very low concentrations (< 0.3 mM) compared to glucose (about 4 mM). Since the KM's for both are similar, the CNS doesn't begin to use ketone bodies in preference to glucose until their concentration exceed's the concentration of glucose in the serum. The system becomes saturated at about 7 mM. The limiting factor in using ketone bodies then becomes the ability of the liver to synthesis them, which requires the induction of the enzymes required for acetoacetate biosynthesis. Normal glucose concentrations inhibit ketone body synthesis, thus the ketone bodies will only begin to be Continue reading >>
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 >>