2.B) Lyle McDonald - The Ketogenic ziechowhasodi.ml - Ebook download as PDF File .pdf) or read book online. This book is meant as a technical reference manual for the ketogenic diet. Lyle McDonald Bio: Lyle McDonald received his B.S. from the University of. Thread: Just Read "The Ketogenic Diet" by Lyle McDonald. During the week when I will be in Ketosis, should I eat low GI carbs if I do even .. ziechowhasodi.ml com/diet/ebooks/ziechowhasodi.ml[/url].
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It is meant to be a reference manual for low-carbohydrate diets; it is unlike any other . Rather than glorifying the ketogenic diet, Lyle McDonald gives you the. Does anyone have a PDF version of Lyle Mcdonalds "The Ketogenic Diet". I bought the book for about $ Canadian a while ago, brought it along to read for. The Ketogenic Diet: A Complete Guide for the Dieter and Practitioner [Lyle McDonald] on ziechowhasodi.ml *FREE* shipping on qualifying offers. 'The Ketogenic.
Use of the guidelines herein is at the sole choice and risk of the reader. All rights reserved. This book or any part thereof, may not be reproduced or recorded in any form without permission in writing from the publisher, except for brief quotations embodied in critical articles or reviews.
For information contact: Lyle McDonald, E. Anderson Ln. Mauro DiPasquale, and before them Michael Zumpano, who did the initial work on the ketogenic diet for athletes and got me interested in researching them. Without their initial work, this book would never have been written. Special thanks to the numerous individuals on the internet especially the lowcarb-l list , who asked me the hard questions and forced me to go look for answers. To those same individuals, thank you for your patience as I have finished this book.
Extra special thanks go out to my editors, Elzi Volk and Clair Melton. Your input has been invaluable, and prevented me from being redundant.
Thanks also goes out to everybody who has sent me corrections through the various printings. Even more thanks to Lisa Sporleder, who provided me valuable input on page layout, and without whom this book would have looked far worse. Finally, a special acknowledgement goes to Robert Langford, who developed the 10 day ketogenic diet cycle which appears on pages Since that time, I have spent innumerable hours researching the details of the diet, attempting to answer the many questions which surround it.
This book represents the results of that quest. The ketogenic diet is surrounded by controversy.
Proponents of the ketogenic diet proclaim it as a magical diet while opponents denounce the diet because of misconceptions about the physiology involved. As with so many issues of controversy, the reality is somewhere in the middle.
Like most dietary approaches, the ketogenic diet has benefits and drawbacks, all of which are discussed in this book. The goal of this book is not to convince nor dissuade individuals to use a ketogenic diet. Rather, the goal of this book is to present the facts behind the ketogenic diet based on the available scientific research.
While the use of anecdotal evidence is minimized, it is included where it adds to the information presented. Guidelines for implementing the ketogenic diet are presented for those individuals who decide to use it.
Although a diet free of carbohydrates is appropriate for individuals who are not exercising or only performing low-intensity aerobic exercise, it is not appropriate for those individuals involved in high-intensity exercise.
As discussed in the next chapter, an adequate protein intake during the first weeks of a ketogenic diet will prevent muscle loss by supplying the amino acids for gluconeogenesis that would otherwise come from body proteins. By extension, under conditions of low glucose availability, if glucose requirements go down due to increases in alternative fuels such as FFA and ketones, the need for gluconeogenesis from protein will also decrease.
The circumstances under which this occurs are discussed below. Arguably the major adaptation to the ketogenic diet is a decrease in glucose use by the body, which exerts a protein sparing effect 2. This is discussed in greater detail in chapter 5. This includes skeletal muscle, the heart, and most organs. However, there are other tissues such as the brain, red blood cells, the renal medulla, bone marrow and Type II muscle fibers which cannot use FFA and require glucose 2. The fact that the brain is incapable of using FFA for fuel has led to one of the biggest misconceptions about human physiology: While it is true that the brain normally runs on glucose, the brain will readily use ketones for fuel if they are available In all likelihood, ketones exist primarily to provide a fat-derived fuel for the brain during periods when carbohydrates are unavailable 2,7.
As with glucose and FFA, the utilization of ketones is related to their availability 7. Under normal dietary conditions, ketone concentrations are so low that ketones provide a negligible amount of energy to the tissues of the body 5,8. If ketone concentrations increase, most tissues in the body will begin to derive some portion of their energy requirements from ketones 9.
Some research also suggests that ketones are the preferred fuel of many tissues 9. One exception is the liver which does not use ketones for fuel, relying instead on FFA 7,10, By the third day of ketosis, all of the non-protein fuel is derived from the oxidation of FFA and ketones 12, As ketosis develops, most tissues which can use ketones for fuel will stop using them to a significant degree by the third week 7,9.
This decrease in ketone utilization occurs due to a down regulation of the enzymes responsible for ketone use and occurs in all tissues except the brain 7. After three weeks, most tissues will meet their energy requirements almost exclusively through the breakdown of FFA 9. This is thought to be an adaptation to ensure adequate ketone levels for the brain. Except in the case of Type I diabetes, ketones will only be present in the bloodstream under conditions where FFA use by the body has increased.
For all practical purposes we can assume that a large increase in FFA use is accompanied by an increase in ketone utilization and these two fuels can be considered together. Relationships between carbohydrates and fat Excess dietary carbohydrates can be converted to fat in the liver through a process called de novo lipognesis DNL.
As long as muscle and liver glycogen stores are not completely filled, the body is able to store or burn off excess dietary carbohydrates. Of course this process occurs at the expense of limiting fat burning, meaning that any dietary fat which is ingested with a high carbohydrate intake is stored as fat.
Under certain circumstances, excess dietary carbohydrate can go through DNL, and be stored in fat cells although the contribution to fat gain is thought to be minimal Those circumstances occur when muscle and liver glycogen levels are filled and there is an excess of carbohydrate being consumed.
As well, the combination of inactivity with a very high carbohydrate AND high fat diet is much worse in terms of fat gain. With chronically overfilled glycogen stores and a high carbohydrate intake, fat utilization is almost completely blocked and any dietary fat consumed is stored.
This has led some authors to suggest an absolute minimization of dietary fat for weight loss 15, The premise is that, since incoming carbohydrate will block fat burning by the body, less fat must be eaten to avoid storage. The ketogenic diet approaches this problem from the opposite direction. By reducing carbohydrate intake to minimum levels, fat utilization by the body is maximized.
Section 3: Factors influencing fuel utilization There are several factors which affect the mix of fuels used by the body. The primary factor is the amount of each nutrient protein, carbohydrate, fat and alcohol being consumed and this impacts on the other three factors The second determinant is the levels of hormones such as insulin and glucagon, which are directly related to the mix of foods being consumed. Finally the levels of regulatory enzymes for glucose and fat breakdown, which are beyond our control except through changes in diet and activity, determine the overall use of each fuel.
Each of these factors are discussed in detail below. As stated above, the body will tend to utilize a given fuel for energy in relation to its availability and concentration in the bloodstream.
In general, the body can increase or decrease its use of glucose in direct proportion to the amount of dietary carbohydrate being consumed. This is an attempt to maintain body glycogen stores at a certain level If carbohydrate consumption increases, carbohydrate use will go up and vice versa. Protein is slightly less regulated When protein intake goes up, protein oxidation will also go up to some degree.
By the same token, if protein intake drops, the body will use less protein for fuel. This is an attempt to maintain body protein stores at constant levels. In contrast, the amount of dietary fat being eaten does not significantly increase the amount of fat used for fuel by the body. Rather fat oxidation is determined indirectly: Similarly the consumption of carbohydrate affects the amount of fat used by the body for fuel.
A high carbohydrate diet decreases the use of fat for fuel and vice versa Thus, the greatest rates of fat oxidation will occur under conditions when carbohydrates are restricted. As well, the level of muscle glycogen regulates how much fat is used by the muscle 20,21 , a topic discussed in chapter Hormone levels There are a host of regulatory hormones which determine fuel use in the human body.
The primary hormone is insulin and its levels, to a great degree, determine the levels of other hormones and the overall metabolism of the body 2,16, A brief examination of the major hormones involved in fuel use appears below.
Insulin is a peptide protein based hormone released from the pancreas, primarily in response to increases in blood glucose. When blood glucose increases, insulin levels increase as well, causing glucose in the bloodstream to be stored as glycogen in the muscle or liver. Excess glucose can be pushed into fat cells for storage as alpha-glycerophosphate. Protein synthesis is stimulated and free amino acids the building blocks of proteins are be moved into muscle cells and incorporated into larger proteins.
Fat synthesis called lipogenesis and fat storage are both stimulated. FFA release from fat cells is inhibited by even small amounts of insulin. When blood glucose increases outside of this range, insulin is released to lower blood glucose back to normal. The greatest increase in blood glucose levels and the greatest increase in insulin occurs from the consumption of dietary carbohydrates.
Protein causes a smaller increase in insulin output because some individual amino acids can be converted to glucose. FFA can stimulate insulin release as can high concentrations of ketone bodies although to a much lesser degree than carbohydrate or protein. This is discussed in chapter 4. When insulin drops and other hormones such as glucagon increase, the body will break down stored fuels.
Triglyceride stored in fat cells is broken down into FFA and glycerol and released into the bloodstream.
Proteins may be broken down into individual amino acids and used to produce glucose. Glycogen stored in the liver is broken down into glucose and released into the bloodstream 2.
These substances can then be used for fuel in the body. Type I diabetics suffer from a defect in the pancreas leaving them completely without the ability to make or release insulin.
IDDM diabetics must inject themselves with insulin to maintain blood glucose within normal levels. This will become important when the distinction between diabetic ketoacidosis and dietary induced ketosis is made in the next chapter. Like insulin, glucagon is also a peptide hormone released from the pancreas and its primary role is also to maintain blood glucose levels. However, glucagon acts by raising blood glucose when it drops below normal. High levels of insulin inhibit the pancreas from releasing glucagon.
Under normal conditions, glucagon has very little effect in tissues other than the liver i. However, when insulin is very low, as occurs with carbohydrate restriction and exercise, glucagon plays a minor role in muscle glycogen breakdown as well as fat mobilization. In addition to its primary role in maintaining blood glucose under conditions of low blood sugar, glucagon also plays a pivotal role in ketone body formation in the liver, discussed in detail in the next chapter. From the above descriptions, it should be clear that insulin and glucagon play antagonistic roles to one another.
As a general rule, when insulin is high, glucagon levels are low. By the same token, if insulin levels decrease, glucagon will increase. This ratio is an important factor in the discussion of ketogenesis in the next chapter. While insulin and glucagon play the major roles in determining the anabolic or catabolic state of the body, there are several other hormones which play additional roles.
They are briefly discussed here. Growth hormone GH is another peptide hormone which has numerous effects on the body, both on tissue growth as well as fuel mobilization. GH is released in response to a variety of stressors the most important of which for our purposes are exercise, a decrease in blood glucose, and carbohydrate restriction or fasting.
As its name suggests, GH is a growth promoting hormone, increasing protein synthesis in the muscle and liver. GH also tends to mobilize FFA from fat cells for energy. The primary IGF in the human body is insulin like growth factor-1 IGF-1 which has anabolic effects on most tissues of the body. GH stimulates the liver to produce IGF-1 but only in the presence of insulin. High GH levels along with high insulin levels as would be seen with a protein and carbohydrate containing meal will raise IGF-1 levels as well as increasing anabolic reactions in the body.
To the contrary, high GH levels with low levels of insulin, as seen in fasting or carbohydrate restriction, will not cause an increase in IGF-1 levels. This is one of the reasons that ketogenic diets are not ideal for situations requiring tissue synthesis, such as muscle growth or recovery from certain injuries: There are two thyroid hormones, thyroxine T4 and triiodothyronine T3.
In the human body, T4 is primarily a storage form of T3 and plays few physiological roles itself. The majority of T3 is not released from the thyroid gland but rather is converted from T4 in other tissues, primarily the liver.
Although thyroid hormones affect all tissues of the body, we are primarily concerned with the effects of thyroid on metabolic rate and protein synthesis. The effects of low-carbohydrate diets on levels of thyroid hormones as well as their actions are discussed in chapter 5.
Cortisol is a catabolic hormone released from the adrenal cortex and is involved in many reactions in the body, most related to fuel utilization. Cortisol is involved in the breakdown of protein to glucose as well as being involved in fat breakdown. Although cortisol is absolutely required for life, an excess of cortisol caused by stress and other factors is detrimental in the long term, causing a continuous drain on body proteins including muscle, bone, connective tissue and skin.
Cortisol tends to play a permissive effect in its actions, allowing other hormones to work more effectively. They are generally released in response to stress such as exercise, cold, or fasting. Epinephrine is released primarily from the adrenal medulla, traveling in the bloodstream to exert its effects on most tissues in the body.
Norepinephrine is released primarily from the nerve terminals, exerting its effects only on specific tissues of the body. The interactions of the catecholamines on the various tissues of the body are quite complex and beyond the scope of this book. The primary role that the catecholamines have in terms of the ketogenic diet is to stimulate free fatty acid release from fat cells.
When insulin levels are low, epinephrine and norepinephrine are both involved in fat mobilization. In humans, only insulin and the catecholamines have any real effect on fat mobilization with insulin inhibiting fat breakdown and the catecholamines stimulating fat breakdown.
Liver glycogen The liver is one of the most metabolically active organs in the entire body. All foods coming through the digestive tract are processed initially in the liver.
Additionally, high levels of liver glycogen tends to be associated with higher bodyfat levels The liver is basically a short term storehouse for glycogen which is used to maintain blood glucose. The breakdown of liver glycogen to glucose, to be released into the bloodstream, is stimulated by an increase in glucagon as discussed previously.
When liver glycogen is full, blood glucose is maintained and the body is generally anabolic, which means that incoming glucose, amino acids and free fatty acids are stored as glycogen, proteins, and triglycerides respectively. When liver glycogen becomes depleted, via intensive exercise or the absence of dietary carbohydrates, the liver shifts roles and becomes catabolic.
Glycogen is broken into glucose, proteins are broken down into amino acids, and triglycerides are broken down to free fatty acids.
If liver glycogen is depleted sufficiently, blood glucose drops and the shift in insulin and glucagon occurs. This induces ketone body formation, called ketogenesis, and is discussed in the next chapter. Enzyme levels The final regulator of fuel use in the body is enzyme activity.
Ultimately enzyme levels are determined by the nutrients being ingested in the diet and the hormonal levels which result. For example, when carbohydrates are consumed and insulin is high, the enzymes involved in glucose use and glycogen storage are stimulated and the enzymes involved in fat breakdown are inhibited. By the same token, if insulin drops the enzymes involved in glucose use are inhibited and the enzymes involved in fat breakdown will increase. Long term adaptation to a high carbohydrate or low carbohydrate diet can cause longer term changes in the enzymes involved in fat and carbohydrate use as well.
If an individual consumes no carbohydrates for several weeks, there is a down regulation of enzymes in the liver and muscle which store and burn carbohydrates 1,17, The end result of this is an inability to use carbohydrates for fuel for a short period of time after they are reintroduced to the diet. Summary Although there are four major fuels which the body can use, for our purposes only the interactions between glucose and free fatty acids need to be considered. There are four major factors that regulate fuel use by the body.
Ultimately they are all determined by the intake of dietary carbohydrates. When carbohydrate availability is high, carbohydrate use and storage is high and fat use is low. When carbohydrate availability is low, carbohydrate use and storage is low and fat use is high.
The most basic premise of the ketogenic diet is that the body can be forced to burn greater amounts of fat by decreasing its use of glucose. The adaptations which occur in the body as well as the processes involved are discussed in the next chapter. Cahill G. Starvation in man. N Engl J Med Saunders Company, Owen O.
Brain metabolism during fasting. J Clin Invest Sokoloff L. Metabolism of ketone bodies by the brain. Ann Rev Med Kidney International Mitchell GA et.
Medical aspects of ketone body metabolism. Swink TD et. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev Nosadini R. Ketone body metabolism: A physiological and clinical overview. Krebs HA et. The role of ketone bodies in caloric homeostasis. Adv Enzym Regul 9: Elia M.
Ketone body metabolism in lean male adults during short-term starvation, with particular reference to forearm muscle metabolism. Clinical Science Owen OE et. Protein, fat and carbohydrate requirements during starvation: Hellerstein M. Synthesis of fat in response to alterations in diet: Lipids 31 suppl SS Flatt JP. Use and storage of carbohydrate and fat. Am J Clin Nutr 61 suppl: McCollum Award Lecture, Diet, lifestyle, and weight maintenance.
Randle PJ. Metabolic fuel selection: Proc Nutr Soc Randle PJ et. Glucose fatty acid interactions and the regulation of glucose disposal. J Cell Biochem 55 suppl: Glycogen levels and obesity. Int J Obes 20 suppl: Schrauwen P, et. Role of glycogen-lowering exercise in the change of fat oxidation in response to a high-fat diet. Am J Physiol EE Schrauwen P, et al.
Fat balance in obese subjects: Am J Physiol. Integration of the overall response to exercise. Int J Obes 19 suppl: Cahill GF Jr. Hormone-fuel relationships during fasting.
Cahill GF. Banting Memorial Lecture Physiology of insulin in man. Diabetes Foster D. Basic ketone physiology To understand the adaptations which occur as a result of ketosis, it is necessary to examine the physiology behind the production of ketone bodies in the liver.
As well, an examination of what ketone bodies are and what ketosis represents is necessary. Finally, concerns about ketoacidosis as it occurs in diabetics are addressed. Ketone bodies What are ketone bodies? While ketones can technically be made from certain amino acids, this is not thought to contribute significantly to ketosis 1. Roughly one-third of AcAc is converted to acetone, which is excreted in the breath and urine. As a side note, urinary and breath excretion of acetone is negligible in terms of caloric loss, amounting to a maximum of calories per day 2.
The fact that ketones are excreted through this pathway has led some authors to argue that fat loss is being accomplished through urination and breathing. While this may be very loosely true, in that ketones are produced from the breakdown of fat and energy is being lost through these routes, the number of calories lost per day will have a minimal effect on fat loss.
Functions of ketones in the body Ketones serve a number of functions in the body. The primary role, and arguably the most important to ketogenic dieters, is to replace glucose as a fat-derived fuel for the brain 3,4. A commonly held misconception is that the brain can only use glucose for fuel.
These effects should be seen as a survival mechanism to spare what little glucose is available to the body. The importance of ketones as a brain fuel are discussed in more detail in the next chapter. A second function of ketones is as a fuel for most other tissues in the body. While many tissues of the body especially muscle use a large amount of ketones for fuel during the first few weeks of a ketogenic diet, most of these same tissues will decrease their use of ketones as the length of time in ketosis increases 4.
At this time, these tissues rely primarily on the breakdown of free fatty acids FFA. In practical terms, after three weeks of a ketogenic diet, the use of ketones by tissues other than the brain is negligible and can be ignored.
A potential effect of ketones discussed further in chapter 5 is to inhibit protein breakdown during starvation through several possible mechanisms, discussed in detail in the next chapter.
The only other known function of ketones is as a precursor for lipid synthesis in the brain of neonates 4. Ketogenesis and the two site model The formation of ketone bodies, called ketogenesis, is at the heart of the ketogenic diet and the processes involved need to be understood.
As described in the previous chapter, the primary regulators of ketone body formation are the hormones insulin and glucagon.
The shift that occurs in these two hormones, a decrease in insulin and an increase in glucagon is one of the major regulating steps regulating ketogenesis. A great amount of research has been performed to determine exactly what is involved in ketogenesis. All the research has led to a model involving two sites: For our purposes, MHS and its effects are unimportant so we will focus only on the first two sites of regulation: The fat cell As discussed in the previous chapter, the breakdown of fat in fat cells, is determined primarily by the hormones insulin and the catecholamines.
When insulin is high, free fatty acid mobilization is inhibited and fat storage is stimulated through the enzyme lipoprotein lipase LPL. When insulin decreases, free fatty acids FFA are mobilized both due to the absence of insulin as well as the presence of lipolytic fat mobilizing hormones such as the catecholamines 9, Glucagon, cortisol and growth hormone play additional but minor roles. Insulin has a much stronger anti-lipolytic effect than the catecholamines have a lipolytic effect.
If insulin is high, even though catecholamines are high as well, lipolysis is blocked. It is generally rare to have high levels of both insulin and catecholamines in the body. This is because the stimuli to raise catecholamine levels, such as exercise, tend to lower insulin and vice versa.
Breakdown and transport of Triglyceride 11 When the proper signal reaches the fat cell, stored triglyceride TG is broken down into glycerol and three free fatty acid FFA chains. Once in the bloodstream, FFA can be used for energy production by most tissues of the body, with the exception of the brain and a few others.
If there is sufficient FFA and the liver is prepared to produce ketone bodies, ketones are produced and released into the bloodstream. The fat cell should be considered one regulatory site for ketone body formation in that a lack of adequate FFA will prevent ketones from being made in the liver. That is, even if the liver is in a mode to synthesize ketone bodies, a lack of FFA will prevent the development of ketosis.
The liver The liver is always producing ketones to some small degree and they are always present in the bloodstream.
Under normal dietary conditions, ketone concentrations are simply too low to be of any physiological consequence.
A ketogenic diet increases the amount of ketones which are produced and the blood concentrations seen. Thus ketones should not be considered a toxic substance or a byproduct of abnormal human metabolism. Rather, ketones are a normal physiological substance that plays many important roles in the human body. The liver is the second site involved in ketogenesis and arguably the more important of the two. Even in the presence of high FFA levels, if the liver is not in a ketogenic mode, ketones will not be produced.
The major determinant of whether the liver will produce ketone bodies is the amount of liver glycogen present 8. The primary role of liver glycogen is to maintain normal blood glucose levels. When dietary carbohydrates are removed from the diet and blood glucose falls, glucagon signals the liver to break down its glycogen stores to glucose which is released into the bloodstream.
After approximately hours, depending on activity, liver glycogen is almost completely depleted. At this time, ketogenesis increases rapidly. In fact, after liver glycogen is depleted, the availability of FFA will determine the rate of ketone production. When carbohydrates are consumed, insulin levels are high and glucagon levels are low. Glycogen storage is stimulated and fat synthesis in the liver will occur.
Fat breakdown is inhibited both in the fat cell as well as in the liver 8. When carbohydrates are removed from the diet, liver glycogen will eventually be emptied as the body tries to maintain blood glucose levels. Blood glucose will drop as liver glycogen is depleted.
As blood glucose decreases, insulin will decrease and glucagon will increase. As insulin drops, FFA are mobilized from the fat cell, providing adequate substrate for the liver to make ketones. The liver has the capacity to produce from to grams of ketones per day once ketogenesis has been initiated 4, Additionally, the liver is producing ketones at a maximal rate by the third day of carbohydrate restriction It appears that once the liver has become ketogenic, the rate of ketone body formation is determined solely by the rate of incoming FFA This will have implications for the effects of exercise on levels of ketosis see chapter 21 for more details.
Figure 1 graphically illustrates the 2 site model of ketogenesis. Figure 1: CPT-1 is responsible for carrying free fatty acids into the mitochondria to be burned.
Technical note: Malonyl-CoA is an intermediate in fat synthesis which is present in high amounts when liver glycogen is high. When the liver is full of glycogen, fat synthesis lipogenesis is high and fat breakdown lipolysis is low 8. Malonyl-CoA levels ultimately determine whether the liver begins producing ketone bodies or not.
This occurs because malonyl-CoA inhibits the action of an enzyme called carnitine palmityl tranferase 1 CPT-1 both in the liver and other tissues such as muscle 8, When carbohydrate is available, acetyl-CoA is used to produce more energy in the Krebs cycle. When carbohydrate is not available, acetyl-CoA cannot enter the Krebs cycle and will accumulate in the liver figure 2. Figure 2: Ketosis and Ketoacidosis Having discussed the mechanisms behind ketone body production, we can now examine the metabolic state of ketosis, and what it represents.
Additionally, ketosis is contrasted to runaway diabetic ketoacidosis. What is ketosis? Ketosis occurs in a number of physiological states including fasting called starvation ketosis , the consumption of a high fat diet called dietary ketosis , and immediately after exercise called post-exercise ketosis. Two pathological and potentially fatal metabolic states during which ketosis occurs are diabetic ketoacidosis and alcoholic ketoacidosis.
Starvation and dietary ketosis will normally not progress to dangerous levels, due to various feedback loops which are present in the body Diabetic and alcoholic ketoacidosis are both potentially fatal conditions All ketotic states ultimately occur for the same reasons.
The first is a reduction of the hormone insulin and an increase in the hormone glucagon both of which are dependent on the depletion of liver glycogen.
The second is an increase in FFA availability to the liver, either from dietary fat or the release of stored bodyfat. Under normal conditions, ketone bodies are present in the bloodstream in minute amounts, approximately 0. When ketone body formation increases in the liver, ketones begin to accumulate in the bloodstream. Ketosis is defined clinically as a ketone concentration above 0. Mild ketosis, around 2 mmol, also occurs following aerobic exercise.
The impact of exercise on ketosis is discussed in chapter Diabetic and alcoholic ketoacidosis result in ketone concentrations up to 25 mmol 6. This level of ketosis will never occur in non-diabetic or alcoholic individuals A summary of the different ketone body concentrations appears in table 1. Ketone body concentrations are higher in fasting than during a ketogenic diet due to the slight insulin response from eating.
Data is from Mitchell GA et al. Ketonemia and ketonuria The general metabolic state of ketosis can be further subdivided into two categories. The first is ketonemia which describes the buildup of ketone bodies in the bloodstream. Technically ketonemia is the true indicator that ketosis has been induced. However the only way to measure the level of ketonemia is with a blood test which is not practical for ketogenic dieters. The second subdivision is ketonuria which describes the buildup and excretion of ketone bodies in the urine, which occurs due to the accumulation of ketones in the kidney.
However, this may only amount to grams of total ketones excreted per day Since ketones have a caloric value of 4. The degree of ketonuria, which is an indirect indicator of ketonemia, can be measured by the use of Ketostix tm , small paper strips which react with urinary ketones and change color.
Ketonemia will always occur before ketonuria. Ketone concentrations tend to vary throughout the day and are generally lower in the morning, reaching a peak around midnight 6. This may occur from changes in hormone levels throughout the day Additionally, women appear to show deeper ketone levels than men 19,20 and children develop deeper ketosis than do adults 5. Finally, certain supplements, such as N-acetyl-cysteine, a popular anti-oxidant, can falsely indicate ketosis 4. Some individuals, who have followed all of the guidelines for establishing ketosis will not show urinary ketones.
However this does not mean that they are not technically in ketosis. Ketonuria is only an indirect measure of ketone concentrations in the bloodstream and Ketostix tm measurements can be inaccurate see chapter 15 for more details. What does ketosis represent? The development of ketosis indicates two things. First, it indicates that the body has shifted from a metabolism relying primarily on carbohydrates for fuel to one using primarily fat and ketones for fuel 4.
This is arguably the main goal of the ketogenic diet: The reasons this shift may be desirable are discussed in the next chapter. Second, ketosis indicates that the entire pathway of fat breakdown is intact 4. The absence of ketosis under conditions which are known to induce it would indicate that a flaw in fat breakdown exists somewhere in the chain from fat breakdown, to transport, to oxidation in the liver. This absence would indicate a metabolic abnormality requiring further evaluation.
Blood pH and ketoacidosis A major concern that frequently arises with regards to ketogenic diets is related to the slight acidification caused by the accumulation of ketone bodies in the bloodstream.
Normal blood pH is 7. While blood pH does temporarily decrease, the body attains normal pH levels within a few days 21 as long as ketone body concentrations do not exceed mmol Although blood pH is normalized after a few days, the buffering capacity of the blood is decreased 21 , which has implications for exercise as discussed in chapters 18 through There is frequent confusion between the dietary ketosis seen during a ketogenic diet and the pathological and potentially fatal state of diabetic ketoacidosis DKA.
DKA occurs only in Type I diabetes, a disease characterized by a defect in the pancreas, whereby insulin cannot be produced.
Type I diabetics must take insulin injections to maintain normal blood glucose levels. In diabetics who are without insulin for some time, a state that is similar to dietary ketosis begins to develop but with several differences.
Additionally, the complete lack of insulin in Type I diabetics appears to further increase ketone body formation in these individuals. While a non-diabetic individual may produce grams of ketones per day 4,16 , Type I diabetics have been found to produce up to grams of ketones per day 22, The drop in blood pH seen in DKA is probably related to the overproduction of ketones under these circumstances Presumably this occurs because blood glucose is present in adequate amounts making glucose the preferred fuel.
Thus there is a situation where ketone body formation is high but ketone body utilization by the body is very low, causing a rapid buildup of ketones in the bloodstream. Additionally, in non-diabetic individuals there are at least two feedback loops to prevent runaway ketoacidosis from occurring.
When ketones reach high concentrations in the bloodstream approximately mmol , they stimulate a release of insulin 8, This increase in insulin has three major effects First, it slows FFA release from the fat cell.
Third, it increases the excretion of ketones into the urine. These three effects all serve to lower blood ketone body concentration. In addition to stimulating insulin release, ketones appear to have an impact directly on the fat cell, slowing FFA release 12, This would serve to limit FFA availability to the liver, slowing ketone body formation. Ultimately these two feedback loops prevent the non-diabetic individual from overproducing ketones since high ketone levels decrease ketone body formation.
Type I diabetics lack both of these feedback loops. Their inability to release insulin from the pancreas prevents high ketone body levels from regulating their own production. The clinical treatment for DKA is insulin injection which rapidly shuts down ketone body formation in the liver, slows FFA release from fat cells, and pushes ketones out of the bloodstream Additionally, rehydration and electrolyte supplementation is necessary to correct for the effects of DKA The feedback loops present in a non-insulin using individual will prevent metabolic ketosis from ever reaching the levels of runaway DKA Table 2 compares the major differences between a normal diet, dietary ketosis and diabetic ketoacidosis.
Table 2: Alcoholic KA occurs in individuals who have gone without food while drinking heavily 4. Ethanol also has effects on ketone body formation by the liver, causing a runaway ketotic state similar to DKA In contrast to DKA, alcoholic ketoacidosis can be easily reversed by eating carbohydrates as this increases insulin and stops ketone formation 4.
The presence of ketosis indicates that fat breakdown has been activated in the body and that the entire pathway of fat degradation is intact.
The lack of ketosis in states such as fasting and a ketogenic diet known to induce ketosis would indicate the presence of a metabolic abnormality.
Ketosis can be delineated into ketonemia, the presence of ketones in the bloodstream, and ketonuria, the presence of ketones in the urine. Clinically, ketosis is defined as a ketone concentration of 0. A ketogenic diet or fasting will result in ketone levels between 4 and 8 mmol. Ketoacidosis is defined as 8 mmol or higher and pathological ketoacidosis, as in diabetic ketoacidosis, can result in ketone concentrations of 20 mmol or greater.
Ketoacidosis, as it occurs in Type I diabetics and alcoholics and which is potentially fatal, will not occur in non- diabetic individuals due to built in feedback loops whereby excess ketones stimulate the release of insulin, slowing ketone body formation.
References Cited 1. Council on Foods and Nutrition. A critique of low-carbohydrate ketogenic weight reducing regimes. Haymond MW et. Effects of ketosis on glucose flux in children and adults. EE 6. Miles JM et. Suppression of glucose production and stimulation of insulin secretion by physiological concentrations of ketone bodies in man.
J Clin Endocrin Metab Wolfe RR et. Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects. Jenson MD et. Lipolysis during fasting: Decreased suppression by insulin and increased stimulation by epinephrine. Theory and Practice 5th ed. Porte D and Sherwin R. Appleton and Lange, McGarry JD et.
Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Fery F et. Hormonal and metabolic changes induced by an isocaloric isoprotienic ketogenic diet in healthy subjects.
Diabete Metab 8: On the maximal possible rate of ketogenesis. Garber A. Hepatic ketogenesis and gluconeogenesis in humans. Reichard GA et. Ketone-body production and oxidation in fasting obese humans. Ubukata E et. Diurnal variations in blood ketone bodies in insulin-resistant diabetes mellitus and noninsulin-dependent diabetes mellitus patients: Ann Nutr Metab Merimee T. Sex variations in free fatty acids and ketones during fasting: Homeostasis during fasting II: Hormone substrate differences between men and women.
J Clin Endocrinol Metab Balasse EO and Fery F. Ketone body production and disposal: Misbin RI. Ketoacids and the insulin receptor.
Keller U. Human ketone body production and utilization studied using tracer techniques: Adaptations to Ketosis Having discussed the basics of fuel utilization, ketone body formation and ketosis, it is now time to examine in detail the adaptations which occur in shifting the body away from glucose and towards fat metabolism.
The primary adaptation occurs in the brain although other systems are affected as well. There is a common misconception, especially among bodybuilders, that ketosis is indicative of protein breakdown when in fact the exact opposite is the case. The development of ketosis sets in motion a series of adaptations which minimize body protein losses during periods of caloric deprivation.
In fact, preventing the development of ketosis during these periods increases protein losses from the body. The adaptations to ketosis are complex and involve most systems of the body. As with the previous sections, smaller details are ignored for this discussion and interested readers should examine the references provided.
While this is an extreme state, the lack of food intake makes it simpler to examine the major adaptations. To help individuals understand the adaptations to ketosis, the metabolism of the body is examined during both short and long term fasting. The next chapter discusses the effects of food intake on ketosis, as well as body composition changes.
An overview of starvation Starvation and the ketogenic diet In one sense, the ketogenic diet is identical to starvation, except that food is being consumed. That is, the metabolic effects which occur and the adaptations which are seen during starvation are roughly identical to what is seen during a ketogenic diet.
The primary difference is that the protein and fat intake of a ketogenic diet will replace some of the protein and fat which would otherwise be used for fuel during starvation. The response to total starvation has been extensively studied, arguably moreso than the ketogenic diet itself. For this reason the great majority of data presented below comes from studies of individuals who are fasting. With few exceptions, which are noted as necessary, the metabolic effects of a ketogenic diet are identical to what occurs during starvation.
The amounts of protein and fat are less critical in this regard see chapter 9 for more details. A brief overview of the adaptations to starvation 4 Before looking in detail at the adaptations to starvation, we will briefly discuss the major events which occur. Starvation can be broken into 5 distinct phases. In the first phase, during the first 8 hours of starvation, the body is still absorbing fuel from previous meals. In the second phase, the first day or two of starvation, the body will rely on FFA and the breakdown of liver glycogen for its energy requirements.
Liver glycogen is typically gone within hours. In the third phase, during the first week of starvation, the body will drastically increase the production of glucose from protein and other fuels such as lactate, pyruvate and glycerol.
This is called gluconeogenesis the making of new glucose and is discussed in detail below. At the same time, tissues other than the brain are decreasing their use of glucose, relying on FFA and ketones instead. This helps to spare what little glucose is available for the brain.
During this phase, protein breakdown increases greatly. The fourth phase of starvation is ketosis, which begins during the third or fourth day of starvation, and continues as long as carbohydrates are restricted. The major adaptations during ketosis is increased utilization of ketones by the brain. The final phase, which begins in the second week, is marked by decreasing protein breakdown and gluconeogenesis, as the major protein sparing adaptations to ketosis occur.
With the exception of the initial hours of carbohydrate restriction phases 1 and 2 , each of the above phases is discussed in more detail below.
Changes in hormones and fuel availability Although some mention is made in the discussions below of the adaptations seen during this time period, most of the major adaptations to ketosis start to occur by the third day, continuing for at least 3 weeks Both remain constant for the duration of the fast.
One thing to note is that the body strives to maintain near-normal blood glucose levels even under conditions of total fasting 5. Additionally, the popular belief that there is no insulin present on a ketogenic diet is incorrect 7. This most likely occurs due to the conversion of dietary protein to glucose in the liver. Cortisol may actually decrease This increases the rate of fat breakdown and blood levels of FFA and ketones increase 6,8,10,14, Although the liver is producing ketones at its maximum rate by day three 14 , blood ketone levels will continue to increase finally reaching a plateau by three weeks 6.
The decrease in blood glucose and subsequent increase in FFA and ketones appear to be the signal for the adaptations which are seen, and which are discussed below In addition to increases in FFA and ketones, there are changes in blood levels of some amino acids AAs.
Increases are seen in the the branch chain amino acids, indicating increased protein breakdown 1, As well, there are decreases in other AAs, especially alanine 1, 10, This most likely represents increased removal by the liver but may also be caused by decreased release of alanine from the muscles This is discussed in further detail in section 3. Changes in levels of the other amino acids also occur and interested readers should examine the references cited.
Blood levels of urea, a breakdown product of protein also increase 1. All of this data points to increased protein breakdown during the initial stages of starvation. By the third day of carbohydrate restriction, the body is no longer using an appreciable amount of glucose for fuel.
At this time essentially all of the non-protein energy is being derived from the oxidation of fat, both directly from FFA and indirectly via ketone bodies Changes in ketone and fat usage during starvation The changes which occur in ketone and FFA utilization during starvation are different for short and long term starvation.
Both are discussed below. For an individual with a metabolic rate of calories per day, roughly calories of FFA approximately grams of fat are used to fuel the body. Considering that one pound of fat contains 3, calories, this represents a loss of almost two-thirds of a pound of fat per day. Smaller individuals with lower metabolic rates will use proportionally less fat. While this extreme rate of fat loss makes starvation attractive as a treatment for obesity, the problems associated with total fasting especially body protein loss make it unacceptable.
The ketogenic diet is an attempt to harness this shift to cause maximum fat loss and minimum muscle loss, as discussed in greater detail in the upcoming sections. Fat and ketone use during long term starvation Most tissues except the brain, stop using ketones for fuel after the third week of ketosis. This is especially true for skeletal muscle.
This is thought to occur for the following reason. During the first few days of ketosis, the brain is incapable of using ketones for fuel. By using a large amount of ketones for fuel, skeletal muscle prevents a rapid increase in blood ketone levels, which might cause acidosis. As time passes and the brain adapts to using ketones for fuel, skeletal muscle must stop using ketones for fuel, to avoid depriving the brain of fuel.
For all practical purposes, with long term starvation, the primary fuel of all tissues except the brain and the others mentioned in section 3 is FFA, not ketones. This is a critical adaptation for two reasons. First and foremost, there are tissues in the body which can not use FFA for fuel, requiring glucose.
By decreasing their use of glucose, those tissues which do not require glucose for energy spare what little is available for the tissue which do require it. Thus, there is always a small requirement for glucose under any condition.
As we shall see, this small glucose requirement can easily be met without the consumption of carbohydrates. The second reason is that a reduction in protein losses is critical to survival during total starvation. The loss of too much muscle tissue will eventually cause death 6. To examine the adaptations to ketosis in terms of glucose and protein, we first need to discuss which tissues do and do not require glucose. Then the adaptations which occur during starvation, in terms of the conservation of glucose, can be examined.
Which tissues use glucose? All tissues in the body have the capacity to use glucose. With the exception of the brain and a few other tissues leukocytes, bone marrow, erythrocytes , all tissues in the body can use FFA or ketones for fuel when carbohydrate is not available 5, The CNS and brain are the largest consumers of glucose on a daily basis, requiring roughly grams of glucose per day 5, This peculiarity of brain metabolism has led to probably the most important misconception regarding the ketogenic diet.
A commonly heard statement is that the brain can only use glucose for fuel but this is only conditionally true. It has been known for over 30 years that, once ketosis has been established for a few days, the brain will derive more and more of its fuel requirements from ketones, finally deriving over half of its energy needs from ketones with the remainder coming from glucose 6,26, This raises the question of how much glucose is required by the body and whether or not this amount can be provided on a diet completely devoid of carbohydrate.
How much carbohydrate per day is needed to sustain the body? When carbohydrate is removed from the diet, the body undergoes at least three major adaptations to conserve what little glucose and protein it does have 5.
The primary adaptation is an overall shift in fuel utilization from glucose to FFA in most tissues, as discussed in the previous section 5,6. This shift spares what little glucose is available to fuel the brain. The second adaptation occurs in the leukocytes, erythrocytes and bone marrow which continue to use glucose 6.
To prevent a depletion of available glucose stores, these tissues break down glucose partially to lactate and pyruvate which go to the liver and are recycled back to glucose again 5,6.
This means that any diet which contains less than grams of carbohydrate per day will induce ketosis, the depth of which will depend on how many carbohydrates are consumed i. During the initial stages of ketosis, any carbohydrate intake below grams will induce ketosis The question which requires an answer is this: What sources of glucose does the body have other than the ingestion of dietary carbohydrate?
Put differently, assuming zero dietary carbohydrate intake, can the body produce enough glucose to sustain itself? The impact and implications of exercise on carbohydrate requirements is discussed in later chapters. The few differences between complete fasting and a ketogenic diet are discussed afterwards.
We will assume for the following discussion that liver glycogen has been depleted, ketosis established, and that the only source of glucose is from endogenous fuel stores i.
The effects of food intake on ketosis is discussed in chapter 9. Glycerol comes from the breakdown of adipose tissue triglyceride, lactate and pyruvate from the breakdown of glycogen and glucose, and alanine and glutamine are released from muscle. Since we are ultimately concerned with the loss of muscle tissue during ketosis, gluconeogenesis from alanine and glutamine are discussed further. Alanine is absorbed by the liver, converted to glucose and released back into the bloodstream.
Glutamine is converted to glucose in the kidney 8. There are also increases in blood levels of the branch-chain amino acids, indicating the breakdown of skeletal muscle During the initial weeks of starvation, there is an excretion of 12 grams of nitrogen per day. After even 1 week of starvation, blood alanine levels begin to drop and uptake by the kidneys decreases, indicating that the body is already trying to spare protein losses As glucose production in the liver is decreasing, there is increased glucose production in the kidney Because of these adaptations, nitrogen losses decrease to grams per day by the third week of starvation, indicating the breakdown of approximately 20 grams of body protein 6.
With extremely long term starvation, nitrogen losses may drop to 1 gram per day 7 , indicating the breakdown of only 6 grams of body protein. However at no time does protein breakdown decrease to zero, as there is always a small requirement for glucose As we shall see in a later section, the development of ketosis during starvation is critical for protein sparing.