Dr. Joe Anderson: Yeah, thanks for having me. I m excited to have this conversation.

Transcription

1 Testing Ketosis and the Fat Burning State Guest: Joe Anderson, PhD The contents of this presentation are for informational purposes only and are not intended to be a substitute for professional medical advice, diagnosis, or treatment. This presentation does not provide medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Dr. David Jockers: Welcome, everybody, to the Keto Edge Summit where we are dispelling the myths, helping you overcome the hurdles, and empowering you to improve your brain and your body through the ketogenic lifestyle. I m your host, Dr. David Jockers. I m really excited about today s interview because we re going to be talking with a research expert and somebody that really has been studying how to measure ketosis, nutritional ketosis for a long time now and has published different studies associated with that. And we re going to really dive into that topic in detail. So I want to welcome my guest. This is Dr. Joe Anderson. Dr. Joe, great to have you on today. Dr. Joe Anderson: Yeah, thanks for having me. I m excited to have this conversation. Dr. Jockers: Yeah, for sure. And so Dr. Joe is one of the few breath science leaders in the world. He s bringing deep experience in pulmonary physiology and breath research science to our Keto Edge Summit. He s the owner of Anderson Bioscience and is an affiliate faculty member in the bioengineering department at the University of Washington where he also obtained his PhD in chemical engineering. He s published over 40 peer-reviewed publications. So All rights reserved. 1

2 that s quite a number of studies to publish and quite a background that he has. Joe led the development of breath protocols, performed clinical trials, and structured science and physiology goals for the development of a cutting-edge breath ketone analyzer called the LEVL. And we re going to talk about that in today s interview. Joe is responsible for taking the research he performs and helping LEVL, the company LEVL, translate that into protocols to help improve individuals metabolic and fat-burning state. Joe s strategic vision and deep expertise have been an immense driver in LEVL s success. And so, Dr. Joe, great to have you on. I really wanted to bring you on because we wanted to dive into this topic of really how to understand measurement of breath acetone, ketosis, and really how people can track how they re burning fat. I think that s a really important topic that we re going to dive into in today s interview. But first, tell us your story, how you really got into pulmonary physiology and this science. Dr. Anderson: Yeah, I ll just try to keep it quick. My background was in chemical engineering. And I went to graduate school to get a degree that would have some biology component in it. So the gentleman I worked with had actually invented the home kidney dialysis machine back in the late 60s. And he was so successful, he was actually nominated for a Nobel prize from that research. But he d had a great relationship with the medical school. And his project that he was working on, when I was entering graduate school, was on how did chemicals move in the lungs and come out in the exhaled breath. And really what the goal of the project that they were on was using mathematical analysis to understand that. So that s where it started. And then I moved into a lot of experimental stuff with those groups. And then, over the course of multiple different research fellowships and faculty positions, have continued to do that work. Dr. Jockers: Yeah, absolutely, it s fascinating work, that s for sure. And how does the ketogenic diet and lifestyle really impact the gases in our breath? Let s talk about that. Dr. Anderson: Sure. So the ketogenic lifestyle, essentially, what we re talking about there, is moving from burning mostly sugars to burning fats. So that conversion from sugars to fats means that some things have to happen in All rights reserved. 2

3 your body. And one of those is you have to generate fuel for your brain. Your brains typically rely on carbohydrates for fuel. But when those get shut off or restricted, then fats need to fuel that brain, but the fats can t be used as fuel for the brain. So what happens in the body is the body will convert some of those fats into chemicals that can be used for brain fuel, which are these ketone bodies. That happens in the liver. The mother chemical is called acetyl acetate. That gets converted. And then that gets broken down into two other chemicals. One is beta-hydroxybutyrate. And then both those, the acetyl acetate and betahydroxybutyrate remain in the blood or the liquids of the body. Acetyl acetate also is converted into acetone, which is small. And that comes out in the exhaled breath. So that s what we were talking about when we re talking about these ketone bodies, when we re talking about ketosis, is chemicals that can be used for brain fuel that then appear to help us understand how much fat we re metabolizing. Dr. Jockers: Right, absolutely, so you mentioned basically the three major ketones, which are acetic acid, acetyl acetate, I should say, and acetone, and beta-hydroxybutyrate. And so when it comes to measurement of ketones, most people are familiar, or at least most people talk about blood ketones as a major measurement with beta-hydroxybutyrate. And so your science has really looked into measuring acetone, which is less invasive because you don t have a blood draw. But we ll dive into that in more detail. But that s really what you focused on to measure out the fat-burning state. And so when we talk about the ketogenic lifestyle, what kind of conditions can be impacted by ketosis? Dr. Anderson: Well, in terms, of So let me make sure. What medical conditions you use ketosis to resolve those conditions or help improve those conditions? Sure. There are quite a few. The first one that came up is really epilepsy. And this was, probably almost 100 years ago, they realized getting people off sugar and starting to put them on a higher-fat diet could reduce the epileptic events, the seizures. And the recession of those or refractory, is what they call it, can be almost 80%, I believe, in terms of people having episodes. So it s pretty effective in that, and particularly for children All rights reserved. 3

4 So that was the first place where they found it to be effective. They, in some sense, ditched it in the 70s and 80s when we thought fat was bad, but we ve come back to it really with some vigor recently. The other ones are, for example, type II diabetes. A lot of people think type II diabetes can be called sugar diabetes because sugar s causing that problem. So there s a company, even now, that s really working on a large scale roll out of putting people on ketogenic diets to reverse type II diabetes. And they re having success when people are compliant. When people say, Yes, I m going to get off sugar, and I m going to elevate my ketone bodies, that can work. Other ones are such as cancer. And we can go into some detail, all sorts of different cancers. Some are more effective or more sensitive to the ketosis than others: brain issues Parkinson s, Alzheimer s, just simple dementia, and then, as well as just metabolic disease. So, for example, if you have some sort of metabolic issue that you think is caused by sugar, or maybe your chain of metabolism, there s a defect in that, you can sometimes overcome that with ketosis, as well. All of these, a lot of times, for example, cancer, you d use ketosis in combination with the current state of medical treatment, which would be chemotherapy. So the two together, a lot of times, have a better outcome than just one by itself. Dr. Jockers: Yeah, so it s an adjunctive therapy, a foundational technique there. And what s cool about this summit is we ve got experts in all those areas. We ve got a cardiologist talking about using a ketogenic lifestyle to help impact heart disease. We ve got a diabetes expert talking about how to use it for diabetes. We ve got cancer experts and researchers talking about how to use it for cancer. So really every chronic, inflammatory condition, we can use this sort of foundational lifestyle to help improve. And that s what s really, really exciting. And so let s go back into measuring ketones. And so what are the major ways that people can measure their state of ketosis? Dr. Anderson: Yeah, and one of the things, if I can just take one step back, the question in between these two is you have these conditions where you know ketosis can be beneficial. And then the question that you typically will have is, Well, how much do I need to have? What is what we call the therapeutic dose? So you get to the point, before we go to how to measure them, you get to the point of, I got to measure them because it s not like a pill I take. I take a 50-milligram tablet. And I m on my way All rights reserved. 4

5 Everyone s body, how they process those macronutrients the sugars, the proteins, etc. is going to be different. So the level of ketosis is going to be different. So that s, if you re trying to tailor for a cancer therapeutic, you re going to say, I ve got to exceed a certain threshold for me to get that benefit. Or if I m going to take it for type II diabetes reversal, what threshold do I have to get to? How do I get there? How is my body responding to this, etcetera? So that s the motivation to say, You know, there is a place, a really good place for measuring ketone bodies in your breath, in your blood, etc. And so to get to your question is there are different ways to measure them. The classic way is to measure acetyl acetate in the urine. And I bring that up because really that s probably the poorest way by far. And there s a couple of reasons for that. Number one, your state of hydration is really important. If you re dehydrated, the concentration s going to be higher, etcetera. If you ve just urinated recently, it s hard to urinate again because it s coming out in your urine. So it depends on when you need to go to the bathroom, so to speak. Privacy s obviously an issue because you re going to be doing it behind closed walls. But probably the biggest one is just simply the measurement that it provides is color coded. So there s no quantitative, meaning it s not providing you a value. And so it s hard to track and trend and trying to really understand what s going on. So you move from that to blood, beta-hydroxybutyrate, which is the, really at this point, is somewhat the gold standard because we ve been using it for so long. And that s a nice measurement because you can get a quantitative value. And so you can get a number that you take. However, the drawbacks of it are, and you already mentioned it, you ve got to poke your finger. And at first blush, you may say, Well, I m just pricking my fingers. It s not a big deal. But we ve done quite a few of these. And you get bruised pretty fast, which is, it s just disappointing. And then the other thing that s disappointing is the cost of those strips is fairly expensive. And so if you mess up a measurement, which happens periodically, you ve got to pay for that cost. And it can be $3 a strip, $4 a strip. So it s not insignificant. And then the other thing that s interesting, too, is there s really no device that allows you to easily track and trend those measurements, which can be somewhat difficult, as well. Dr. Jockers: Mmm, yeah All rights reserved. 5

6 Dr. Anderson: So the final one is the one we re working on is the breath acetone. And that s with the LEVL. I can certainly go through that, as well. Dr. Jockers: Yeah, we want to know. For me, personally, I ve been tracking ketones for a long time. And I freak out every single time I m trying to do a blood draw. M y stress hormones go up. It s a stressful event for me. Part of the ketogenic lifestyle is minimizing unnecessary stress. So for some individuals, it s probably not that big a deal. But for other individuals, it really is a big deal when we try to prick our finger. And so that s where coming in with some sort of non-invasive, effective way, because again like you said, you re in ketones. As your body gets more keto-adapted, you re going to produce less of the acetyl acetate. So it s not a good measurement. It s not really a good measurement of how your body s using ketones, for sure. So it really just tells you if you re producing them or not. So we had to find something else. And so let s talk about breath acetate levels. Dr. Anderson: Yeah, so the breath acetone is nice, obviously, because you can provide it with any breath. Any breath that you can make back-to-back measurements, as you re breathing, in some sense, and so very fairly noninvasive. We do provide a breath breathing pattern because we want to get the most repeatable and accurate measurement of that breath sample. So that s helpful. But the nice thing is, it s a simple breath. You capture the last part of your breath. Put it into the device. It makes a measurement. It shows you a measurement on the device. And then it pushes the measurement to your phone, which then you can track and trend. And you can also send that measurement to other apps that potentially can integrate that measurement with body fat measurement, exercise, sleep, etc. So there s quite a bit of utility with that. The reason the device was created initially, and I forgot to say one reason for measuring ketone bodies, is to understand fat loss. So the idea is you re trying to burn more fat. How do you know every single day you re on that right path? Because most people, myself included, you make a measurement at day one. And then you may make a measurement on the scale day 14. And if your body weight changes, that s success. But probably most of us, body weight doesn t change. And so then you look back and say, Well, I ve wasted two weeks. And I don t know what happened or what caused my failure, that s where the breath acetone measurement can help you say, Hey, All rights reserved. 6

7 I m burning all these levels of fat every single day. And if you do fall off the wagon, you can catch that almost immediately and make changes to make sure that you continue on that path. So the breath acetone, that was the initial reason it was developed. Now, there s obviously some other great reasons why measurement of ketosis and breath acetone can be beneficial that we ve talked about. But that s where the LEVL device fits in. Dr. Jockers: Yeah, and just like you said, there s so much variability in how we respond to different meals, stressors in our life, fasting, all this kind of stuff. And so that s why it s not just the cookie-cutter lifestyle, there s unique modifications that need to be made based on a number of different factors. And so testing really is critical. I ve had so many different clients that are like, Hey, I m following ketogenic diet, yet I m not losing weight. I m following ketogenic diet, yet I feel hungry all the time. And so they re getting a lot of these types of reactions that are not really congruent with necessarily following a long-term ketogenic lifestyle. Normally, we shouldn t have constant hunger and cravings. Normally, we should have steady fat loss is we re following it correctly. And so I always ask them, Have you tested your ketones? And typically, the answer is no. Typically, they re not testing it. And they re just following certain guidelines. And the advantage of being able to test regularly really helps us understand how somebody is responding to different things. And when it comes to blood ketones, because of the cost and the invasiveness, I ve always told people, Test, maybe two to three times a day. And there s advantages of doing that. But like, Hey, if we can do something where we re able to test first thing in the morning, before our first meal, directly after the first meal, maybe an hour afterwards, it s going to help us understand how the body s responding to that particular meal, the foods that are in there. In a sense, almost like the cortisol awakening response in the morning, if they re overshooting cortisol, increasing blood sugar. There are so many different factors that could be negating results that they re looking for and blocking and inhibiting their bodies ability to produce adequate amount of ketones to get the desired effect that are hard to figure out without consistent testing. And so being able to test with something accurate through like breath ketones, on a consistent basis, multiple times, 5, All rights reserved. 7

8 10, 15 times throughout the day, I see that as really helping fill in the gap to figure these things out. And so why is calibration, because I know with the LEVL device, there is just consistent approach towards calibration, why is that so important when we re doing breath acetone testing? Dr. Anderson: Yeah, the accuracy comes from the calibration. And I definitely want to talk about that. But let me go back to what you said because you said a lot of things about the measurement, which I think are really important. And they really are what add a lot of value from the LEVL device. For example, the idea of making multiple measurements throughout the day is fantastic because as a user, you may find, Hey, there s something I m doing during the day. And I m forgetting I m doing. For example, what we found, which is not uncommon, people unconsciously eat sometimes. Sometimes they go, and they have that drawer of candy that they just pull something from. They don t even think about it. And they eat it, which obviously kills their ketogenic diet. It kills their weight loss program, etc. And that s something, if you re making those multiple measurements, you can capture that because, as people, sometimes we lie to ourselves. And so that can be a good way to track and find out, You know, I am messing up at nighttime. Rewarding myself with a piece of chocolate cake every night because I ve done a good job throughout the day really is killing my diet. So that s one thing. The second, it keeps us honest. The second thing is because the data gets pushed to a larger database, you, Dr. Jockers, as a coach, can actually look at your clients and help them along, and say, Hey, you know what? There s this time on Thursday that you re having problems. Let s talk about that. And let s use We like to say, every reading is a good reading, whether it s high or low. And so it allows you to say, Hey, let s talk about that. Let s have a good conversation. And maybe there s something I can do for you and have ways to navigate those tough situations, whether it be stress, or the attempt to eat things that you shouldn t be eating, or not sleeping, etc. And then the final thing, I think is fantastic with lots of measurements, is you understand your own body. That s really what this biomarker s all about is its internal. It lets you know how your genetics, which is forming your machinery All rights reserved. 8

9 to burn fats and all other chemicals, allows those to be transitioned. So you can understand your machinery by making these measurements. And that s really one of the most powerful things. And then to go to your question is, How do you know that measurement is accurate and reliable? Well, and the way you do that, with any measurement really, is and LEVL s no different is to calibrate the measurement. And so we have these canisters that have known concentrations of acetone in them that you put across the device to make sure our LEVL device is measuring 2 parts per million, 4 parts per million with great accuracy so that then when you put your unknown sample, which is coming from your breath, it simply has to make a comparison to those known concentrations. Dr. Jockers: Yeah, absolutely, and it s so important to get that consistency and that accuracy. We can talk all day just about the importance of, really going back to the other question, the variability, because I will see so many people with different food sensitivities. For example, eggs are a great ketogenic food, but I ve seen a lot of people with food sensitivities to eggs. And so they were eating eggs. And it was actually causing a stress response in their body, which increased their blood glucose and insulin levels, which blocked their body s ability to burn fat and produce ketones. And so it s hard to figure that out on your own. But if you are eating a meal with eggs, normally that should keep you or help promote a fat-burning state in your body as long as if it s a low-carb meal like just, for example, just some scrambled eggs, or hard-boiled eggs, or something like that, it s the kind of meal that s going to promote fat burning and ketone production. However, if you re not getting those results with it, if you re testing an hour or two, three hours after and you re not getting results, it s a sign that for whatever reason your body had a stress response, blood sugar went up, you re not burning the fat that you re supposed to. And if you ve got specific weightloss goals, also you ll be able to see actually how well you re burning fat. And again, we need a system because there are other breath analyzers out there. And I ve used them, and other people have, as well. And what I found was very inconsistent results that I was getting. And so with the LEVL, it really intrigued me because of just the major effort towards accuracy and that consistent calibration to make sure that whatever you were breathing into the meter was actually the result that you were getting All rights reserved. 9

10 Dr. Anderson: Yeah, that s exactly, you hit on multiple topics. And one of them really goes to the point of everybody is different. And the guidelines we have, which are great guidelines for the population as a whole, may or may not work for the individual. And most likely, they re not all going to work for any individual, but it s a good baseline to start from. Like you said eggs seem like a great place to start for burning fat. As a matter of fact, I eat them all the time. But they may not be the best for everyone, like you said, because you may have an allergy. Or they may, in fact, the other piece is, some people may put things on those eggs that kill their fat metabolism that you wouldn t think for the population would kill fat metabolism. But for that individual, adding cheese to the egg, may not be what needs to happen to have that good, effective fat metabolism. And then like you said, is you re right. The second piece isn t necessarily the sample, so to speak, and how that sample gets created due to changing your diet and exercise. The other piece is the measurement side. You re right, the calibration is so key for any chemical measurement. And that s why we spent so much time to make sure that this is an accurate measurement with calibration. With time, we d like to move away from having to do the calibration at all. But that may not happen because the measurements we re doing are such low values. We re talking one molecule of acetone in a million molecules, which is a really very fine and sensitive measurement. So in some sense, calibration has to be done because it s such a fine measurement. Dr. Jockers: Yeah, and obviously the calibration is one of the most important distinguishing factors between the LEVL and other breath acetone meters. So what are some of the other distinguishing factors? Dr. Anderson: Yeah, the other things that we ve really focused on are getting a great sample. And that s one of the things where my background comes in very well is to have people take in a deeper breath, hold their breath for a period of time. It s about five seconds. It allows the acetone to equilibrate to get well mixed in the lungs and then provide a very comfortable, large exhalation. Now, all these pieces, inhalation, and breath hold, exhalation, they should all be comfortable. They should be something that you can do every single time you provide a breath sample. You don t have to take in a huge breath, hold it, All rights reserved. 10

11 then a huge exhalation. That s not what we re trying to do here. It s just something that s comfortable that s repeatable, etcetera. And the reason that s effective is what we ve shown is the repeatability of breath-to-breath is a tenth of a parts per million. So.1 part per million difference in the repeat measurements from breath-to-breath from our data. So that s an important one is the comfortable breath sample that can be repeated. The other one we found, accuracy is obviously very important and then the ability to track and trend these values, not only on your device, but also pairing it with other platforms out there that can allow you to integrate information. We have the ability on ours to add your weight and your body fat mass. But there are other things people want to integrate. And then I think the last thing, as well, like I said earlier, is once that data s on the Web. The coach can access it and view all their clients and say, You know what? If Betsy have a tough day on Thursday, and I ve been seeing that happen, I need to contact her. And Joanne s doing a great time the entire time. But Sam, you know what? He s not even close, right. So we ve got to have a good conversation on how we get started up and get him moving towards where he needs to be. So all those pieces from accuracy to ease of measurement to tracking and trending to use by the coach, I think, are all things that really provide a lot of value with the LEVL device. Dr. Jockers: Yeah, absolutely, definitely important things because again the goal here is it s a biofeedback device. And I ve found, clinically, working with patients, the most important thing is getting that proper biofeedback on a regular basis helps that individual really understand how to master their body. And really the health journey, in general, when we re trying to accomplish health goals, I tell people it s like getting a master s degree in your own health. You re going to invest time, money, and energy into doing it. And you have to look at it like that. You re not a pill away. You re not a week of dieting away. Instead it s a lifestyle approach. And the goal is to learn as much as possible about your own body and your own unique traits and characteristics and how you respond to certain stressors and foods. And biofeedback devices, such as the LEVL are extremely helpful All rights reserved. 11

12 So with that, I know we ve been talking about the LEVL. And I d love to see a demonstration of this. I m sure our audience would as well. So I know you ve got one right there with you. Dr. Anderson: Yeah, so here s the Let s see if I can put it up here. Here s the LEVL device. It s about the size of a Kleenex box, in some sense. Inside of it, you ve got two breath ports. So this one is one just uses for storage. This is the one that you re going to put the breath pod in when you re ready to make the measurements. And then, essentially, I ll even do a measurement here. We ve got user one. Hopefully, you can see that. It says user 2 and then guest mode. So you can have multiple different users and guests. But here s the breath pod. I ll take that out. And basically, the breath pod, you can open it up and just empty inside. And it s going to just simply capture the air coming out of your mouth. I ll put in a mouthpiece because if you use it in your home, you may want to have a mouthpiece or if you use it at a gym or something. But we have two breath pods that come with the device. So like I said, we also have an App. Let me just make sure I m paired here. Dr. Jockers: So the two breath pods, they re both calibrated. And one of them is saying, Okay, this is kind of standard. And then, you re breathing in to show the difference, in a sense. Dr. Anderson: Yeah, we do the calibration before. Even use just this simple breath pod. And once the calibration s done, then it s ready for you to put a breath sample in and ready to go. So I m going to do that. Deeper breath in, hold it for five seconds, then a big comfortable exhalation. Then we ll put it in to the device here. Let me just make sure we re ready to go. Okay. [Demonstrates breathing technique]. And then simply put this into the device there. And we re going to close the lid. And you can see it s starting the measurement. So what that s doing is it s simply pulling the breath across the sensor and making the measurement of acetone. It takes about 20 seconds. So I ll put that down. I don t imagine my breath acetone concentration would be very large today. And it s not. So you can see it says one there on the LEVL device. And if I show you the App I don t know if you can read that it s.9, which is about 1. You can see old measurements of mine right here across the bottom. So other measurements I ve made. And then, as we scroll up, it tracks and trends All rights reserved. 12

13 different measurements below. I haven t made a lot of measurements recently because I ve been out of town, but that gives you the whole reading there. And then from the App, it gets sent out to the Cloud. And like I said, it can show up on a If the user gives your coach access, the coach can look at a dashboard and see all their clients and see that measurement. Dr. Jockers: Yes, this is really helpful for nutritionists, dieticians, anybody that s looking to be a keto coach, personal trainers, doctors like myself because again we re able to track it. And it s something that that individual, if the client has it right in their house, they can be doing it throughout the day. And the keto coach can take a look at it every day, every other day, every once a week, once every two weeks, as often as needed to track what s going on, and especially if that person s got some sort of a journal going with it like a meal plan journal where they re writing about that or stress levels in their life and tailoring the results on the LEVL, the breath acetone levels, along with their nutrition and lifestyle trends. So it s really cool. Dr. Anderson: Yeah, that s exactly it. And it gives you another touch point with your clients where you don t have to have face-to-face time, but you do you have the ability remotely to interact with them and make sure they know you re interested in what s going on. You really want to help promote their lifestyle. That s why you guys are in this business. There s no doubt about it. That s why we all are. Without having to take up a lot of time, but keep those nudges happening to make sure they continue on that right path. Yeah. Dr. Jockers: Yeah, absolutely, I see it as an extremely helpful tool. Let s talk about the breath acetone spectrum. I know we had a conversation about that last week. And I was excited to really learn more on this interview about what you re doing with the research with the breath acetone spectrum. Dr. Anderson: Yeah, and it leads naturally from where we re at, too, because one of the things you said is, How can you elevate breath acetone, or what foods, what diet, what stressors, sleep, all those things, what s causing the What are the best ways to elevate breath acetone, and essentially elevate fat metabolism? So what we ve done is I put together, through the literature, what values of breath acetone you d see based on different large-scale events. And one of the reasons that was a driver was a lot of physicians, when you talk to them about, Hey, we have a device that measures acetone in breath, they have All rights reserved. 13

14 this frown. And they said, Why would you ever want to do that? If someone has acetone on their breath, they should be going to the emergency room because that means they re in diabetic ketoacidosis, which I m sure a lot of people understand. Some may not. But the reality is, is in fact, there s a big spectrum. There s a big range of acetone in breath that you can get to before you ever get to that edge of saying, Oh, you know what? You re in a condition where you d probably need to go to the ER. And so that s what we did with this publication. Everyone has about one to two parts per million of acetone in their breath. It doesn t matter what diet they re on. That s where you d expect someone to be. And you just saw, it s.9 parts per million, which is not surprising, not for me. But as you start to transition into an elevated state of fat metabolism, that just may be, Hey, I m going to eat a Standard American Diet. It s going to be a mix of carbohydrates, proteins, and fats, but I m going to cut back my calories a little bit, calorie restriction. Then you could see somewhere between 2 and 10 parts per million elevation. And really, what that s associated with, it could be tracked with fat loss. And that was one of the reasons we were excited about the LEVL device. There s a nice study back in the early 90s that s showing the actual, the level of acetone in your breath let s say it s 2 parts per million is correlated with a halfpound of fat mass loss per week. So for folks who just want to do calorie restriction, that 2 to 10 parts per million can be a great range to be in to help you understand, Am I on the right path to lose fat mass? Okay, so that s that range. The next range is really from 10 to 100. And you find that in folks who are fasting. So it can be intermittent fasting. It can be a three-day or seven-day fast. They ve cut down all foods from intake. The other side of that coin can be someone who s removed all sugars. So you re on a ketogenic diet. You re eating higher fats. You re going to eat some protein. You can get in that 10 to 100 parts per million of acetone by elevating your fat metabolism through a ketogenic diet. And then when you really start to see this diabetic ketoacidosis, I would say it s somewhere between 300 and 1250 parts per million. So you re talking 100- fold higher than where you re at if you re just simply eating the Standard American Diet, a really different range. And obviously, it s not the acetone All rights reserved. 14

15 that s causing the debilitating effects. It s the underlying diabetic condition that s causing acidosis in the blood. It s causing some metabolic disturbances that are then perpetuated themselves into these expressions of acetone in the exhaled breath. But the underlying condition is what s really causing the problem. It s not the acetone per se. So those are the different places you can be. The other one I ll mention, I haven t talked about it yet, is the exogenous ketones or the medium-chain triglycerides ingested. And those are probably going to force your body into that 10 to 100 parts per million acetone range, too. But those are going to be maybe short lived, depending on how often you eat the medium-chain triglycerides and the exogenous ketones. Dr. Jockers: Yeah, cool, really, really cool stuff. And let s talk about how the LEVL can take the breath acetone levels (so parts per million) and then convert that into fat loss and fat burned, in a sense. Dr. Anderson: Right, and that goes back to that paper. So the first thing I ll say is one of the things we ve done is published a review paper on breath acetone and fat metabolism. And that you can find on the LEVL Now website. I know you have a copy, too, Dr. Jockers, so I m sure you d be happy to share that. But what it does is talks through all the different science that s gone on in the last 50 years. And this is one of the publications by a gentleman named Kundu. He was a scientist out of Abbott Laboratories in the early 90s. And he did a nice study with about 80 to 100 subjects showing that folks who were on calorierestricted diets, if they are losing fat mass, their acetone levels go up in proportion to the amount of fat lost per week. So like I said, a 2 part per million, which is just a mild elevation in breath acetone and when I say mild, even though I say mild, it doesn t mean it s not somewhat difficult to get to, as folks will understand but if you can get to 2 parts per million on a calorie-restricted, mixed diet, you re expected to lose about a half pound of fat mass per week. If you get to 4 parts per million, it s about a one pound of fat mass. And what I mean, pound, I mean actually pounds of fat, not pounds of body mass. So you may lose more body mass, which is pretty typical because the water starts to come off when you get rid of the sugars. So that s where this correlation between the two happens. And it s really around this calorie restriction phase of dieting All rights reserved. 15

16 Dr. Jockers: Yeah, and that s important, too, because when people start on a ketogenic lifestyle, oftentimes, especially people that are overweight, are obese, that need to lose weight quickly, they do lose weight quickly. But a lot of it s water weight. Then they hit a certain plateau. And then this can really help us understand what s happening there with the plateau because again that initial weight loss, oftentimes, is the water weight. Dr. Anderson: Yeah, that s exactly it. So the water weight s lost. And they get pretty excited. They say, Things are moving forward as I d expect. And then like you said, you get to that plateau. And that s where really, I think, the LEVL device is even more effective because then it allows you to say, Okay, now let s kind of experiment, in a sense. Let s change some of your dietary conditions. So we put you on, like we said, eggs and bacon. Well, maybe let s move it to avocados. Or maybe let s add the medium-chain triglyceride supplement to this. Or maybe there s something else that works in your practice that you ve had success with. And then maybe let s add an extra hour of sleep. Let s try to cut out some of the stress that s causing the increase in cortisol, not allowing your body to increase the fat metabolism. So all those things then, as you as a coach, really that s where the coaching comes in. And it could be really effective. Dr. Jockers: Yeah, and I find that to be extremely effective because, as a functional medicine doctor, myself, I run labs on different people. And labs are great. And they give us a one-time reading of what s happening. Like, if we re looking at adrenals, if we re looking at thyroid, inflammatory levels, we re seeing what s happening right now in the moment with those bodily systems. The cool thing about this is we re able to see what s happening this week, what s happening next week, what s happening throughout the day, what s happening just on a continuous basis, as far as this individual s physiology and their metabolism. So yeah, I find that super helpful. Dr. Anderson: Yeah, you hit the nail on the head. I don t feel and I m not a clinician but I don t feel any clinician really wants to make a medical decision off of one data point. And that s what I think you hit on is you do that blood draw. You get a data point. And you get this nice blood profile, but do you want to make any major changes off of one data point that may or may not be representative of the individual, as a whole? That s why this time series of data points, you can start to feel a little more comfortable, at least in my opinion, to say, Okay, well, let s make some changes. And they don t have to be huge changes. But you have the ability All rights reserved. 16

17 with lots of data that you can then start to analyze and say, Okay, this is working. And that s not working. And let s keep moving you along a path, where that single data point is a tough one to really get a gauge on the individual as a whole. Dr. Jockers: Yeah, absolutely, so as we re talking here, I can see the functional use of this for nutritionists, health coaches, as a ketogenic diet. One of the reasons why we re doing this summit is to really get this message out. And there are a lot of nutritionists, dieticians who are listening to this. Personal trainers, health coaches, a lot of doctors are listening. There also are a lot of lay people that are just interested in the ketogenic lifestyle and how it can benefit them in their lives. And so I know with the LEVL, there are multiple different programs. People can certainly purchase it and have it at their house. Different practitioners can use that in their practices. And so tell us more about how that works, the cost of the system. And let s compare that to other ways of testing ketones as well. Dr. Anderson: Yeah, the one thing I want to bring up first before I talk about the details of it and we forgot to say this is the folks in the company at LEVL, a lot of us came out of the medical device industry or have had experience with that. So one of the things that we found of value is to make this listed with the Food and Drug Administration here in the U.S. So it s an FDA-Class I listed device. And we find great pride in that because it is a medical-grade device in that sense. And so some of this, as a result, there are some costs associated with making it. So two different offerings for the device. One is a home, and one is a professional. And what I mean by the professional is, you as a coach, can have it in your office or gym, etcetera. Clients can come in, make measurements on that whether you are there or not. And like I said, the data then gets shared with you. And you can see it, etc. But that allows the user to bundle in that cost with the cost of your services. And you can provide It s in some sense, people will be able to use it as a business model as well. But it does provide a little more access to the individual. The home device is $699 for the device, $699. And then there s a $50 per month fee that covers the sensors, as well as those calibration canisters to keep the device accurate, the measurement. The professional device, there s a All rights reserved. 17

18 higher monthly fee just to do the ongoing access with the backend, with the management of the digital data. So those are the two different offerings we have. Obviously, they come with all of our tech support, and the other things with the calibration, and the sensor, and that sort of thing. So we find great value in that. And the reason is when you look at the alternative, which is blood, the blood strips are about $3-$4 a measurement. And if you figure out how many measurements you want to do a month, that s going to be pretty costly per month, if you want to get that many measurements. The other nice thing for the LEVL device, as I ve said multiple times, is the non-invasiveness, the tracking and trending, and the interaction with your coaching that really isn t as easily provided with that blood measurement, as well. Dr. Jockers: Yeah, and also, the FDA, just getting that certified by the FDA, I m sure, had a lot of cost because they obviously are going to do all the checks and balances just to make sure that that system is working as it says it is. Dr. Anderson: Yeah, yeah, exactly, the FDA is a huge piece for us. And obviously, because if we want to go in, which we are moving towards some of those medical therapies using the ketogenic diet, having that FDA backing is really critical for us to make sure that we re following all the rules that need to be followed. Dr. Jockers: Yeah, for sure. And so going back to the idea of different ways of testing ketones, you ve got urine testing, which is the most common. So the most common way people get started. But ultimately, it s really not effective, because again, we re not actually testing how the body s using ketones. So really the only two effective approaches are going to be blood ketones and breath acetone levels. And so we know with blood ketones, number one it s invasive. I know for myself, and there s a percentage of people listening that can relate to this, I freak out every time. And I m trying to minimize unnecessary stress. So I don t test blood ketones anymore because of that. Also, I ve seen people with like big calluses because they re constantly testing. And it just damages their fingers. I don t think it s very sustainable. It can definitely be beneficial for a period of time, but the sustainability of that is definitely a lot less. And, of course, like you said, the cost, at this point for All rights reserved. 18

19 blood ketones, if you re doing this on a regular basis, several times a day, you re paying just as much after a month or two as you would with the LEVL. And then, of course, you ve got breath acetone levels. And there are devices out there that I ve had experience with. And I just haven t seen the accuracy be where I wanted it and just very inconsistent readings that I was getting frustrated with. And so I searched on the Internet. And I found the LEVL. And I saw some videos of you guys just really talking about the calibrations and just really this focus on clinical accuracy. And that really intrigued me. And that s why I pursued you, guys. And I got a LEVL for myself and started using this. And that s exactly what I ve seen, as well. There is a calibration, a process that can be a little tedious that goes into it. But it s like riding a bike or something like that. You get used to it after a while. Somebody that s not techy like myself, it took me a little bit. I was on the phone with the support. So having the support help is good, although you guys do make it easy with videos and what not. Watch a couple of few minute videos and it shows you how to do it all. And then, you just get used to the constant calibration. And the results are just continuously accurate. So you can put your trust in that. Dr. Anderson: Yeah, and you brought up a couple of things. You noticed I didn t talk about urine. I usually don t talk about urine because it really isn t a good way to make a measurement. Now, like you said, it s a good way to get started. I ll definitely give you that. But because of the multiple issues with the accuracy of the measurement and how to interpret it In fact, the other one I forgot to say is you re measuring acetyl acetate in the urine. One of the things I talked about from the very beginning is remember acetyl acetate converts into acetone. While the acetyl acetate s in your bladder in the urine, some of that gets converted to acetone, which lowers the concentration that it ultimately measures. So that s another issue. But that s why I don t belabor it because it s a nice way to get introduced, but it really isn t a long-term solution by any means because it doesn t give you any really quantitative data. It s all qualitative. Dr. Jockers: All it tells us is your body s producing ketones. But there s a difference between producing them and using them. You can produce them, but the reality is, if your body doesn t have the metabolic machinery built in order to actually utilize them for energy and for fuel, then you re not getting the results. And so it s not a good measurement. I tell people, Hey, you know what? Ultimately, that s not going to help us. I wouldn t waste your money on All rights reserved. 19

20 urine strips. If you re going to test, do blood or do breath acetone levels. That s what you re looking at there. And again, as somebody who runs lab tests, it s pretty easy for people to spend $600, $700, $800. For three tests, it could be $1,000 just on lab testing. And doing that every three months or so, three to six months, while they re going through their health journey is very common in the functional medicine world. And so if you were to minimize like one of those lab tests, and get something like a LEVL, right there, that just drops your overall lab testing costs and your overall, I guess you could say, your cost of measuring your health status to make tweaks in your lifestyle to get the goals that you wanted, it reduces that overall cost. And that gives you something that gives you continuous feedback. So I see great benefit in that. And this is really a new company. And so you guys just started in what, 2016, 2017, and just are now introducing it to the market? Dr. Anderson: Yeah, we ve been around for a while, but the market, we just introduced it to the market last year. You re right. So in terms of our market rollout, it was last year. And it s taken five to seven years to get it to this point where we could actually put it out in the marketplace because there s a lot of development that went on. But like you said, I think a couple of pieces the cost We do have some other cost structures in terms of breaking that upfront cost out into monthly payments. So that s something to take a look at, as well, on our website. And the other thing I wanted to talk about, like you said, the breath and the blood measurements really are the key ones now. And the breath does align with blood. And that s something we showed in this publication. We re gathering some more data, as we even talk, to show that breath levels of breath acetone are correlated, in a loose sense, with blood betahydroxybutyrate. And one of the markers I give folks, based off of our data, our internal data, is it appears the level data, if you have somewhere between 8 and 10 parts per million, your blood beta-hydroxybutyrate should be around.5 millimoles or greater. As I m giving you some numbers, the folks who kind of understand what these numbers mean are probably more valuable than folks who are just getting initiated to it All rights reserved. 20

21 But that nutritional ketosis level, that s usually defined by that.5 millimoles beta-hydroxybutyrate, as typically seen, from what our data starts to show, is between 8 and 10-parts per million of breath acetone. A little bit different than what you see in the literature. We publish that literature shows a little bit different relationship. But there is a nice relationship between the two. Dr. Jockers: Yeah, so we found the level is basic. Well, in general, nutritional ketosis basically starts at 0.5 millimole per liter of beta-hydroxybutyrate. And your typical nutritional ketosis range is going to be between that and 3.0, depending on what sort of condition we re trying to treat. Sometimes with cancer, we ll get it up higher. But that s typically the range that people are going to be in unless they are doing prolonged fasting when it comes to your blood beta-hydroxybutyrate levels. And so when we look at that, we track it on breath acetone levels, you re saying roughly an 8 to 10 part per million breath acetone level is equivalent to 0.5 beta-hydroxybutyrate blood ketones. And so that s basically about the measurement. And then you, guys are doing more research with that. And eventually, the goal is to have all of that put together. And so it s more concise, as far as where the measurements are. Like, 30 parts per million would be equivalent to roughly, let s say, 3.0 millimole per lister. Yeah, so that s what you guys are looking to do. Dr. Anderson: Yeah, that s exactly it. So we re still gathering more data. And obviously, that relationship may adjust. But the data we have currently seem to indicate that relationship for that nutritional ketosis cut off. And that s important. For example, the diabetic ketoacidosis, the reversal of type 2 diabetes, typically folks need to get you to a.5 millimole betahydroxybutyrate to make sure that you re in the zone that we can start to move folks off of insulin or the other Metformin, etc., to try to get them back on that right path. So yeah, that s a nice cutoff. Dr. Jockers: Well, this is cool stuff. And I m really glad that you re the chief scientific advisor for LEVL because you do research. That s what you do. And that s what you re doing in your full-time job is research and constantly analyzing to come up with graphs and to make the ketogenic lifestyle easier for everybody else All rights reserved. 21