Effects Of Exogenous Ketone Supplementation On Blood Ketone, Glucose, Triglyceride, And Lipoprotein Levels In Sprague–dawley Rats
Abstract Nutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many disease states. We hypothesized that oral administration of exogenous ketone supplements could produce sustained nutritional ketosis (>0.5 mM) without carbohydrate restriction. We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague–Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium β-hydroxybutyrate (βHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5–10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and βHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until βHB returned to baseline. At 28 days, triglycerides, total cholesterol and high-density lipoprotein (HDL) were measured. Exogenous ketone supplementation caused a rapid and sustained elevation of βHB, reduction of glucose, and little change to lipid biomarkers compared to control animals. This study demonstrates the efficacy and tolerability of oral exogenous ketone supplementation in inducing nutritional ketosis independent of dietary restriction. Background Emerging evidence supports the therapeutic potential of the ketogenic diet (KD) for a variety of disease states, leading investigators to research methods of harnessing the benefits of nutritional ketosis without the dietary restrictions. The KD has been used as an effective non-pharmacological therapy for pediatric intractable seizures since the 1920s [1–3]. In addition to epilepsy, the ketogenic diet has elicited significant therapeut Continue reading >>
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What Are Exogenous Ketone Supplements And Are They Worth The Cost?
**all supporting articles are linked in text Great question. Yes we are seeing exogenous ketone supplements all over the place now largely because of the growing popularity of the ketogenic diet. Let’s get into what they do and how to use them. What are Ketones and What is Ketosis? Ketones are fatty acids that your liver produces in mass quantities when you are in a state of ketosis. There are two main ketones that we produce: beta-hydroxybutyrate (BHB) and acetyl-acetate (AcAc). AcAc is created first and get’s converted to BHB creating Acetone as a byproduct that gets released through your breathing. Your body’s preferred source of fuel for your brain is glucose, but if that were all our brains could survive on, we wouldn’t be here. Our primitive ancestors often saw shortages of food and blood glucose, so we developed the ability to burn ketones for fuel. So when our bodies are short on carbohydrate to supply blood glucose, our livers begin converting our fat stores into ketones. You are said to be in a state of nutritional ketosis when your blood ketones rise to between 0.5 and 5mM. To get into a natural state of ketosis, you need to do one of two things: 1) fast for several days to deprive yourself of glucose and kick your body into ketosis, 2) consume a strict high fat, moderate protein, very low carbohydrate diet for a period of 10-21 days ignorer to adapt into ketosis. To learn more about this process, you can get a free keto-adaptation guide by signing up for our newsletter at Exogenous ketone supplements provide a method of getting into short periods of nutritional ketosis without going through these arduous processes. There are two forms of exogenous ketones: esters and salts. As of the writing of this article, esters are still in the experimental phase Continue reading >>
My Experience With Exogenous Ketones: Tale And Truth
97 Comments I woke up the morning of the ceremony with butterflies in my stomach. I’d done the necessary prep. I’d abstained from carbs the past week and food the past 24 hours. I’d performed four consecutive full-body circuit workouts to deplete muscle glycogen, and undergone a liver biopsy to confirm full depletion of liver glycogen. I wasn’t taking any chances. Although I had extensive experience generating endogenous ketones and subsisting on my own body fat, exogenous ketones were another matter entirely. You don’t want to mess around with a holy sacrament without doing due diligence. Holy sacrament? Yes. According to ethnographic accounts from early Arctic explorers who encountered the sacred compound, the exogenous ketone was developed by traditional peoples of the wintry north. No one’s quite sure where it arose first—Siberia, Greenland, Alaska, Lapland. What they do know is that these societies revered the type 1 diabetic, a rare find in the pre-contact Arctic. Using an admittedly grisly and cruel process, these groups would starve the tribe’s diabetic to induce ketoacidosis, harvest the ketone-rich urine, and reduce it slowly to a ketone-rich tar over a wood fire. Tribe shamans would dissolve the tar in pine needle tea and distribute it to members exclusively before hunting trips, warfare, and any other activity requiring optimal physical and mental function to boost energy and improve performance. As Mark Twain famously quipped, “The strongest coffee I ever had was a Laplander’s piss.” So when I showed up to the small building on the edge of town on a rainy evening, I was anxious. What was I in for? The solemn countenances worn by my two guides for the day—Dr. Peter Attia, wearing dark robes and swinging a thurible loaded with burning Continue reading >>
Exogenous Ketones: A Short Review
It is not uncommon for people of all fitness areas looking to lose weight to rave about the topic of a ketogenic diet. Now, a ketogenic diet is basically a method of dieting that is extremely low—not absent—in only carbohydrates for one purpose: to force the body into breaking down fats as energy. This is known as ketosis. When the body is in a state of ketosis, it is not in a state of starvation, but instead has been coerced into utilizing alternative methods of energy production, as opposed to the normal usage of glucose. This method is ketogenesis, or the breakdown of fatty acids into ketone bodies. Ketone bodies in structure are acetoacetate (AcAc), beta-hydroxybutyrate (βHB), and acetone. In the liver, acetyl CoA, the same molecule used to kick off the production of energy via the TCA cycle using glucose, is produced by fatty acid oxidation and is converted into AcAc and βHB. During the process of ketolysis, the ketone bodies that have transferred to non-liver tissue mitochondria are then converted back into acetyl CoA, which will then enter the TCA cycle to produce energy. AcAc and βHB are small enough to go between cell membranes, a necessary component in order to maintain fuel to your brain and peripheral organs during these bouts of dieting or large energy expenditure. Under normal circumstances, people produce ketone bodies once their cells have been depleted of the glycogen stores. The road to utilizing ketone bodies for energy is not without obstacles, as there are factors that influence the utilization of ketone bodies. Differences in tissue and muscle fiber types, actual amount of circulating ketone bodies, compounding nutrition, exercise protocols, as well as conditioning level can all influence the uptake and utilization of ketone bodies. Now, wha Continue reading >>
My Experience With Exogenous Ketones
Last year I wrote a couple of posts on the nuances and complexities of ketosis, with an emphasis on nutritional ketosis (but some discussion of other states of ketosis—starvation ketosis and diabetic ketoacidosis, or DKA). To understand this post, you’ll want to at least be familiar with the ideas in those posts, which can be found here and here. In the second of these posts I discuss the Delta G implications of the body using ketones (specifically, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP generation, instead of glucose and free fatty acid (FFA). At the time I wrote that post I was particularly (read: personally) interested in the Delta G arbitrage. Stated simply, per unit of carbon, utilization of BHB offers more ATP for the same amount of oxygen consumption (as corollary, generation of the same amount of ATP requires less oxygen consumption, when compared to glucose or FFA). I also concluded that post by discussing the possibility of testing this (theoretical) idea in a real person, with the help of exogenous (i.e., synthetic) ketones. I have seen this effect in (unpublished) data in world class athletes not on a ketogenic diet who have supplemented with exogenous ketones (more on that, below). Case after case showed a small, but significant increase in sub-threshold performance (as an example, efforts longer than about 4 minutes all-out). So I decided to find out for myself if ketones could, indeed, offer up the same amount of usable energy with less oxygen consumption. Some housekeeping issues before getting into it. This is a self-experiment, not real “data”—“N of 1” stuff is suggestive, but it prevents the use of nifty little things likes error bars and p-values. Please don’t over interpret these results. My reason for shari Continue reading >>
(diet Review) Pruvit Keto/os Exogenous Ketones: Ketosis Or Not?
I’ve gotten a crazy number of requests do this Pruvit Keto/OS review. Keto/OS is a new exogenous ketone supplement that people are using to lose weight, among other things. I found very little in terms of research on exogenous ketones in humans. Exogenous ketones have been studied a bit in rats, and no one has studied them in terms of weight loss in people or in rodents. The product Keto/OS has no research behind it either, so I decided to bite the bullet and put myself on it for a week to see what would happen. I hate using small studies as proof for anything, but in this case, I had no choice. It was totally an n=1. I also hate drinking disgusting things, but again, in this case I had no choice. Sigh. Before I talk about how that all went, let’s chat about ketones and how they work in your body. What are ketones? Ketones are the byproduct of fat metabolism. When you deprive your body of it’s favorite source of energy – glucose – it starts burning your fat for fuel. That’s the premise of the ketogenic diet: burn fat, use the ketones that result as energy. Staying on the ketogenic diet is tough for most people, but it can be done, and for most healthy people, it’s probably not harmful. Check with your doctor or dietitian before starting any diet. Read my ketogenic diet review here. The issue with ketosis for weight loss is that when you break ketosis, the weight will probably come back on. If you’re a person who lives to eat and not eats to live, it might not be the best weight-loss option for you. Because a ketogenic diet is so difficult for most people to maintain, Pruvit is marketing Keto/OS by saying that you can eat a normal diet, drink Keto/OS, still go into ketosis, and lose weight when your body burns fat for energy from being in ‘ketosis’ fr Continue reading >>
Avoid This Ketogenic Rip-off
The Truth About Exogenous Ketones Ketones are all the rage among low carbers. And like most things in nutrition and performance, we've found a way to get them in supplement form so we don't have to do any actual work. What are ketones? They're a byproduct of ketosis caused by the process of converting fat to fuel. Your body makes them when it's in a calorie or carb restricted state. What do they do? The body and brain can use them as fuel without the presence of glucose in the blood. And now, you can take ketone supplements (salts and esters), known as exogenous ketones, without actually restricting anything. According to those promoting this nasty-tasting supplement, that means you can have a brain and body fuelled by ketones, along with all of the supposed health benefits that come with running on fat. Well, don't fall for it. Exogenous Ketones = Endogenous Fat Storage? The problem with ketone supplementation (EXOgenous) is that it's not even close to the same thing as being in ketosis (ENDOgenous ketone production). And just like the butter-blended-into-coffee trend, it's a farce. Ketones may be depressing dieters' hunger and giving them a hit of energy and cognitive enhancement, but it's INHIBITING their ability to burn fat, providing zero nourishment, and doing nothing for their metabolic health. There's an assortment of evidence suggesting that it's probably making things worse. Think of exogenous ketones kind of like alcohol. When they're consumed, everything is stored and nothing else is burned. So any lipolysis (fat burning) that would be taking place is halted; any glucose and fatty acids in your blood that were circulating are stored; and the ingested ketones are burned until there aren't any left. More importantly, this clearance of alternative fuels (glucos Continue reading >>
Exogenous Ketones: To Ketone Or Not To Ketone
My thoughts on Exogenous Ketones After being contacted (following the Youtube Q&A) by several folks – both members of Ketogains and Internet strangers, I felt compelled to write as fair and even-handed a write-up on exogenous ketone supplementation as I feel can be mustered. I condition my response by saying this – I want to deal only in evidence and hypotheses grounded in biochemistry. I admit up front that this will probably become something of a treatise on what constitutes a well-formulated ketogenic diet. I don’t have the time (or the energy) to put together a document that covers all facets of the use of exogenous ketones in sufficient depth, so what I want to do is to address the folks that I see asking me about them most often – those who have excess body fat, and are looking to lose weight. They have been told about the potential benefits to fat loss via exogenous ketones, and they want to know if the hype is real. Those of you who know me (or read my previous post here) know that I like to respond with “it depends.” So…when the question is raised, “Should I supplement with exogenous ketones?” what do you think my answer will be? Probably not! (HA, I tricked you!)…but let’s explore why. As I’m sure this is going to be hotly debated enough (as the topic is raging in numerous ketogenic groups) there isn’t any value in dealing with speculation that doesn’t have a basis in science, nor in anecdotes. The challenge in dealing with exogenous ketone supplementation is two-fold: One side of the debate has a product to sell. Anytime someone’s livelihood is tied to your purchase of their product, bias and subjective interpretation of the evidence should be considered. The evidence (either for or against) their supplemental use by average schl Continue reading >>
The Pros And Cons Of Exogenous Ketones
Ketones are a hot topic in the fitness and nutrition world right now. They’re a bi-product of fat that’s an alternative fuel source to sugars that’s used by your body when you consume a low carb, high fat diet. Research has shown there’s a number of great benefits of being in ketosis. But, because people (myself and probably you, included), like to get more from doing less, scientists have developed a way to supplement with exogenous ketones. The idea is that you can get the same benefits of eating a low carb, high fat diet without changing your diet. But, is it actually possible to get the same benefits by supplementing with ketones while continuing to eat carbs? In this article, I’ll explore the pros and cons of exogenous ketones to help you find the best approach for your lifestyle. What are Ketones? Ketones or ketone bodies are what’s generated when your body breaks down fat to use as fuel because your carbohydrate intake is low. There are three different types of ketones produced when the body’s in ketosis. These are: READ MORE … Acetoacetate (AcAc) – The first ketone that’s created as your body breaks down fatty acids. Will convert into BHB or acetone. Beta-hydroxybutyric acid (BHB) – BHB technically isn’t a ketone but is used by your body like one. Acetone – Simple side product that breaks down quickly. If it’s not needed for energy, it’ll be removed from the body by waste water or the breath. What are Exogeneous Ketones? Exogeneous just means something that originates from OUTSIDE of the body. So, exogeneous ketones are simply ketones that are ingested, instead of being produced by your body. When it comes to exogeneous ketone supplements, there are two main types: Ketone esters – These are a raw BHB ketone that’s not bound to a Continue reading >>
Are Exogenous Ketones Right For You?
I’ve spent a lot of time lately analysing three thousand ketone vs. glucose data points trying to determine the optimal ketone and blood sugar levels for weight loss, diabetes management, athletic performance and longevity. In this article, I share my insights and learnings on the benefits, side effects and risks of endogenous and endogenous ketosis. But first, I think it’s important to understand the difference between exogenous and endogenous ketosis: Endogenous ketosis occurs when we go without food for a significant period. Our insulin levels drop, and we transition to burning body fat and ketones in our blood rise. Exogenous ketosis occurs when we drink exogenous ketones or consume a ketogenic diet. Ketones are important. As blood glucose decreases, the ketones in your blood increase to keep our energy levels stable. The chart below shows three thousand blood glucose vs ketone values measured at the same time from a range of people following a low carbohydrate or ketogenic diet. While there is generally a linear relationship between glucose and ketones, each person has a unique relationship between their blood glucose and ketone values that provide a unique insight into a particular person’s metabolic health. Hyperinsulinemia has been called as the “unifying theory of chronic disease”     . It’s beneficial to understand where you stand on the spectrum of metabolic health and insulin sensitivity. The chart below shows the typical relationship between blood glucose and blood ketone for a range of different degrees of insulin resistance/sensitivity. If your blood glucose levels are consistently high it’s likely you are not metabolising carbohydrate well. When you go without food, endogenous ketones are slow to kick in because your insulin Continue reading >>
Snr #195: Brendan Egan, Phd – Exogenous Ketone Supplementation
Episode 195: Dr. Brendan Egan of Dublin City University discusses the current research on exogenous ketone supplementation for athletic performance and recovery. Guest Bio Brendan Egan, PhD Brendan holds a position as Senior Lecturer in Sport and Exercise Physiology in the School of Health and Human Performance at Dublin City University. His current research investigates the molecular regulation of skeletal muscle function and adaptation across the life course, with special interest in the synergy between nutrition and exercise interventions to optimise performance in athletes and elderly. He received his BSc Sport and Exercise Science from the University of Limerick in 2003, MSc Sport and Exercise Nutrition from Loughborough University in 2004, and PhD from Dublin City University in 2008, before completing two years of post-doctoral training with Prof. Juleen Zierath’s Integrative Physiology group at the Karolinska Institute, Sweden. His doctoral studies focussed on skeletal muscle adaptation to exercise, and in particular the continuity between acute molecular responses to individual bouts of exercise and adaptations induced by exercise training, whereas his post-doctoral training utilised animal models and in vitro cell systems to investigate the transcriptional regulation of skeletal muscle development and mechanisms of insulin resistance. He joined the faculty in the School of Public Health, Physiotherapy, and Sport Science at University College Dublin in 2011, where he spent five years, and retains a position as Visiting Associate Professor. On the sporting front, he has played inter-county Gaelic football with Sligo since 2003, and consults as a performance nutritionist to elite team sport athletes In This Episode We Discuss: Ketone body definitions Endogenous Continue reading >>
The Different Types Of Ketone Supplements
Within the last few years, ketone supplements have become a popular way to support those following a ketogenic diet and striving to maintain a healthy level of ketosis as much as possible. However, a lot of people still don’t really know about the different types of ketone supplements out there and how they can be beneficial for when you go keto. Understanding ketone supplementation is important because you want to make sure you’re getting the most bang for your buck and avoiding any products that don’t do what they claim. Before describing specific ketone supplements, it will help us to refresh on what are exogenous ketones, and why we should take them. This way, we can better understand the role of these ketone bodies for our own health and weight loss goals. What Are Exogenous Ketone Supplements? Ketone supplements are often referred to as exogenous ketones, meaning they are created externally—outside of the body. This is opposed to the ketones your body produces when carbs are restricted and you’re in a state of ketosis. Basically, exogenous ketones are created in a lab and made into supplement form for you to ingest. There are three ketones the body produces when on a ketogenic diet: acetoacetate, beta-hydroxybutyrate (BHB), and acetone. The ketone found in exogenous ketone supplements is BHB. That’s because the body can use it most efficiently. Now let’s take a look at why exogenous ketones are important and beneficial to a keto diet. Benefits of Exogenous Ketone Supplements There will be times when maintaining a steady ketogenic state isn’t realistic 24/7, so the purpose of ketone supplements is to provide the body with extra ketones to use when you aren’t currently in ketosis. Ketone supplements can be a huge help when transitioning into a stat Continue reading >>
How To Increase Athletic Performance With Exogenous Ketones
Traditional sports nutrition wisdom tells endurance athletes that loading up on carbohydrates prior to long-distance training/events is ideal for optimal performance. However, as sports nutrition research grows, we are learning that there may be more efficacious ways to fuel your endurance training goals. Enter exogenous ketones (Ketone Supplements). The unique nutritional benefits of exogenous ketones, particularly beta-hydroxybutyrate (BHB) salts, are extensive, ranging from nootropic (brain enhancing) properties, enhanced glucose utilisation, physical performance improvements, and reduced inflammation. For endurance athletes, exogenous ketones present a superior nutritional supplement adjunct to pre-training carbohydrate ingestion. If you’re not familiar with what exactly exogenous ketones are and how they work, be sure to check out our FREE Exogenous Ketone eBook that teaches you everything you’ll need to know before moving forward. Why Endurance Athletes Should Use Exogenous Ketones Before we jump into the data behind exogenous ketones and endurance training, let’s get a better grasp of what exactly exogenous ketones do in the human body. In short, ketones are an alternative energy source for your body, specifically mitochondria - the ‘engine’ of cells. While endurance athletes typically think of carb-based sports beverages as the ideal energy source for aerobic exercise, recent studies suggest that exogenous ketones, like BHB salts, bolster the benefits of carbohydrates. In other words, combining ketones with carbohydrates results in better performance and recovery than carbohydrates alone. In fact, adding Essential Amino Acids (EAA’s) like that found in AMINO SWITCH™ may prove to be even more effective as previous studies support the combination of Continue reading >>
The Beginner’s Guide To Exogenous Ketones
Have you been wondering what exogenous ketones are? If so, you’re not the only one. The keto-dieting world has been buzzing with information about developments on exogenous ketones for awhile now, with many brands producing exogenous ketones that are used by Keto lifestylers around the world. But the majority of Keto dieters don’t completely understand what exogenous ketones are or how they can benefit their diet (or dieting options). In this post, we’ll provide you with easy to read information about exogenous ketones. With this knowledge, you’ll be able to utilize exogenous ketones in your diet, and teach others about their value. Let’s start with the label! The Definition of Exogenous Ketones Two words: exogenous and ketones. The word exogenous describes something that is developed from external factors; something outside of the usual production. So in terms of ketones, this means that exogenous ketones are synthetic: created outside of your body by scientists and then ingested for accelerated ketosis. We assume that you already know what ketones are, but just in case, we’ll give you a brief description of this term as well. Ketones, are organic compounds produced by in your body when your system experiences starvation, or when you restrict carbohydrates and increase fats, which inhibits a starvation-like state that produces ketone bodies. These ketones are an ideal fuel source for your body and your brain. Studies have suggested that when your body is in a ketogenic state, it utilizes oxygen more efficiently in the generation of energy. In short, ketones are secret weapons for anyone looking to take their body’s fueling system to the next level! To restate the point: Exogenous Ketones are ketone supplements. They’re created outside of your body and i 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 >>