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The Melanie Avalon Podcast Episode #53- Trey Suntrup (Biosense)

Trey is a researcher and product leader with over 13 years of experience developing novel device technologies in both academic and industrial settings. He joined Readout from his position as an entrepreneur-in-residence at BioGenerator, a St. Louis based venture capital firm.

Previously Trey was a Translational Sciences and Entrepreneurship fellow at Washington University Medical School in St. Louis, where he helped academic faculty transition commercially promising technologies from the lab to the private sector. He also served as an investment analyst for several venture capital firms in the life sciences.

Trey is passionate about partnering with mission-driven founders as they advance new device and digital health technologies to improve patient care. He holds a PhD in physics and electrical engineering from the University of California, Santa Barbara.


LEARN MORE AT:

https://mybiosense.com/
https://www.instagram.com/mybiosense/
https://www.facebook.com/mybiosense/

SHOWNOTES

1:40 -  IF Biohackers: Intermittent Fasting + Real Foods + Life: Join Melanie's Facebook Group For A Weekly Episode GIVEAWAY, And To Discuss And Learn About All Things Biohacking! All Conversations Welcome!

1:55 - Get $20 Off A Biosense Device, At MelanieAvalon.com/Biosense, With The Coupon Code avalon20

2:30 - BEAUTYCOUNTER: Non-Toxic Beauty Products Tested For Heavy Metals, Which Support Skin Health And Look Amazing! Shop At Beautycounter.Com/MelanieAvalon For Something Magical! For Exclusive Offers And Discounts, And More On The Science Of Skincare, Get On Melanie's Private Beauty Counter Email List At MelanieAvalon.Com/CleanBeauty! Find your perfect Beautycounter Products With Melanie's Quiz: Melanieavalon.com/beautycounterquiz

4:20 - LUMEN: Measure Your Breath To Instantly Find Out If You're Burning Carbs Or Fat! Get $50 Off A Lumen Device At MelanieAvalon.com/Lumen With The Code melanieavalon

The Melanie Avalon Podcast Episode #43 - Daniel Tal

6:45 - Trey's Background

9:45 - What Is Ketosis?

11:30 - The Fat Burning Vs Ketogenic State

12:30 - The Problems With The "Nebulous" State

16:00 - Urine, Breath, And Blood Ketones:  Acetoacetate, BHB, And Acetone  

19:05 - Acetoacetate Conversion to BHB vs. Acetone 

21:55 - Recap: Ketone Use By Cells 

22:40 - The Stability Of BHB 

24:00 - Acetoacetate vs BHB as a fuel, And Anti-inflammatory signaling  

25:10 - What Do Urinary Ketones Indicate?

28:00 - Changes in Urinary Ketones Measurements 

29:50 - BHB vs acetone production, Redox Potential, NAD, And longevity 

32:10 - long term keto adaption 

32:35 - SUNLIGHTEN: Get $200 Off Any Sunlighten Cabin Model Or $100 Off The Solo Unit (That Melanie Has!) AND $99 Shipping (Regularly $598) With The Code MelanieAvalon At MelanieAvalon.Com/Sunlighten. Forward Your Proof Of Purchase To Podcast@MelanieAvalon.com, To Receive A Signed Copy Of What When Wine!

The Melanie Avalon Podcast Episode #38 - Connie Zack

34:40 - The Value Of Measuring Breath Vs. Blood

36:40 - Accurate Breath Measurements: Deep Lung Sampling

38:35 - Using Biosense: Personalization 

40:10 - Breath Acetone Correlations To BHB

Characterization of a high-resolution breath acetone meter for ketosis monitoring

44:10 - Ketone Variability Through The Day

46:15- The Time difference between breath and blood  

51:00 - Total Ketone Exposure During A Single Day: the ketone score

54:00 - Exogenous Ketones And MCT oil

56:30 - using ketones as fuel vs Excretion 

#120 – AMA with Dom D’Agostino, Ph.D., Part II of II: Ketosis for cancer and chronic disease, hyperbaric oxygen therapy, and the effect of ketosis on female health

1:00:20 - The Effect Of Exercise  On Ketones

1:01:05 - Biosense Vs. Lumen

LUMEN: Measure Your Breath To Instantly Find Out If You're Burning Carbs Or Fat! Get $50 Off A Lumen Device At MelanieAvalon.com/Lumen With The Code melanieavalon

Breath Acetone as Biomarker for Lipid Oxidation and Early Ketone Detection

1:04:00 - Biosense Ketone Measurements (ACEs)

1:07:45 - Tracking the effect of ketosis in your body (kick on in a higher state of around 10) - signaling benefits

1:09:05 - BiOptimizers: Magnesium Breakthrough:  Get 10% Off The Most Comprehensive Magnesium Supplement Available www.magbreakthrough.com/melanieavalon With The Code Melanie10

The Melanie Avalon Podcast Episode #47 - Wade Lightheart

1:11:30 - OMAD, Carbs And Ketosis 

1:12:20 - Fat and glycogen

From Trey:  "You will want to direct your attention to Figure 4, which shows that RQ stops changing above breath acetone values of 2 ppm (i.e. 2000 ppb). As I mentioned during the interview, 2ppm corresponds to about 3 ACEs on our device (remember that the BIOSENSE range is 0-40 ACEs)." 

1:13:40 - Liver and muscle Glycogen, and ketosis 

1:18:15 - The Importance Of Feedback For Lifestyle Change

1:19:45 - Storing measurements : Using the app, tracking trends, etc. 

1:22:00 - Get $20 Off A Biosense Device, At MelanieAvalon.com/Biosense, With The Coupon Code avalon20 



TRANSCRIPT

Melanie Avalon: Hi friends, welcome back to the show. I am so excited about the topic that we are about to dive deep into. It's a topic which is-- I was thinking about this is probably one of the most popular topics in the biohacking sphere. So, it's a shocker that I haven't had an episode yet dedicated to it. But I think this is going to be the episode for it. I'm very excited because we're going to go into the science, we're going to go into how you can make it applicable and practical in your own life. So, I am here with Trey Suntrup. He is with a company called Biosense. And they make a ketone breath analyzer. So there it is, the teaser. Although I guess if you saw the title of this episode, you probably already know what it's about, but a little bit about Trey.

He is a researcher and a products leader. He has over 13 years of experience developing novel device technologies in academic and industrial settings. He holds a PhD in physics and electrical engineering from the University of California, Santa Barbara. Like I said, he does work with the company, Biosense, and they have a new breath analyzer device to, of course, analyze ketones. One of the reasons I'm really, really looking forward to this episode and the conversation that we're about to have is, there's a lot of questions and suspicions and different ideas out there about measuring ketones, about the ketogenic state, about what is the best way to go about that? What is practical? What is applicable? What does it even mean? I think Trey can hopefully speak to a lot about that. So, Trey, thank you so much for being here.

Trey Suntrup: Thanks so much for having me, Melanie.

Melanie Avalon: Before we jump in, we were talking a little bit before the call about your background and everything. I was wondering if you could tell listeners a little bit about your background, and what brought you to where you are right now with Biosense? What's your history there?

Trey Suntrup: Sure. I'm trained as a physical scientist and engineer. As you mentioned, my PhD is in physics. I spent a lot of time in my academic career looking at devices and how the physics of those devices operate. I did some product workup in Silicon Valley after graduate school, but I really felt I wasn't connecting to the cause as much as I wanted to. What I mean by that is, I didn't draw a straight line between the work that I was doing and benefit to real people. So, I had this idea - how do I break into the medical tech in the healthcare space? And this opportunity came up in my hometown of St. Louis, Missouri, at Washington University here in the medical school. They had a postdoctoral fellowship there that was really interesting. It was NIH funded. It was super open-ended, and I got to work in the medical school doing both clinical research and also helping medical school faculty transition some of their laboratory inventions into commercial technologies. So really at the boundary between academia and industry, which I've always found that transition totally fascinating.

As part of that work, I stumbled upon this technology, working with an investor here in St. Louis, this company Readout Health who had developed Biosense. Long story short, I just ended up doing some work on behalf of the investor on the company, and then they hired me at the end of that work. So, I've been with the company here for about 15 months, and I'm loving it. It's such a fun ride.

Melanie Avalon: I love that so much. Actually, that's a really similar story, because I actually recently on the podcast had another-- He wasn't even ever really a scientist, but entrepreneur in this whole breath-analyzing device, and that was actually the Lumen device which does not measure ketones. We can circle back around to maybe how that compares to Biosense a little bit later in this conversation. But his story was actually really similar as far as the focus was on taking some science from some trials and some studies and then actually making it really practical for the user and the focus on that whole aspect. I think there's just so much benefit to that because we can sit and we can read studies all day about ketosis. We can read studies all day about ketones, all these things, but it's really bringing the applicable science into your hands and experiencing it for you, that I just think is so valuable. I'm really, really excited to discuss all of this.

Before we go into the actual science and studies, for listeners who aren't familiar, even though I feel most listeners will be pretty familiar, would you like to give listeners just a brief overview about what the ketogenic state or ketosis actually is in the body?

Trey Suntrup: Sure, no problem. Normally, there's this thing called the standard American diet that I think everybody's pretty familiar with. It's generally understood to be high carbohydrate, high calorie. When you're eating a diet like that, your body is really deriving its energy from glucose and from those carbohydrates, and that's really the primary fuel source for your body. Actually, whenever excess glucose is available, that's what your body is going to use for energy.

The state of ketosis actually occurs when your body switches from primarily burning carbohydrates to primarily burning fat. This could either be dietary fat in the case of the ketogenic diet, if you're eating a low-carb, high-fat diet, or it could be your own internal fat stores if you're fasting or you're doing deep caloric restriction. So, there's a bunch of benefits, you could imagine, and I'm sure many of your listeners are familiar, with related to anti-inflammatory effects, weight loss, improvement of a bunch of different metabolic markers, improvement in diabetes, the list goes on.

Melanie Avalon: Quick question to that. The fat-burning state versus the ketogenic state when you're burning these ketones, when does that switch happen? Does it vary by the individual? For example, could you be in a fat-burning mode and actually never start to generate ketones? If you're in a fat-burning mode, are you automatically generating ketones? When does the actual ketone-generating process occur?

Trey Suntrup: That's actually a great question and it's one that I really glossed over and I shouldn't have. When you switch off of this primarily glucose burning state, you switch into a state where you're burning both fatty acids and ketones for energy. So, it's actually both that are occurring at the same time. Part of the reason why your body produces ketones instead of just burning fatty acids is that your brain is not able to use fatty acids for metabolism. So, your brain can either use glucose if it's available, or it can use ketones as a metabolic substrate. So, your body came up with this trick where when it starts to metabolize fat in the liver, the liver actually releases these ketone bodies, which are an additional metabolic substrate for your body.

Melanie Avalon: Okay, I'm actually having some epiphanies now. I don't know if you guys have found this in your studies or your work, the actual ketone-generating metabolism process. You just said that the brain can either run on glucose or ketones, but it can't run off of fatty acids. So, is it possible that some people never really tap into a truly ketogenic state for whatever reason that might be, maybe their dietary macros, maybe they're not fasting long enough, not going low carb quite enough, so they're in this nebulous state where they never really start that ketone process while still maybe being lower carb so they get like brain fog? Some people say that they never seem to experience that ketogenic state, no matter how much they try. I'm just wondering if it's possible that if you're not exactly doing the macros that you need to be doing or doing the fasting that you need to be doing, you could think that you're getting into ketosis, but you're not?

Trey Suntrup: Absolutely, yeah. It's a great question. I totally understand what you mean. I do think on that transition point between the glucose burning and the fat and the ketone state, there's this fuzzy area where your glucose may drop, but you haven't ramped up to ketone production yet. And to your point, if your brain starts to not have enough energy in the form of-- you don't have the glucose but you don't have the ketones yet, then that could control to some of that brain fog that you're talking about. The other reasons have to do with when you restrict carbohydrates, your electrolytes get thrown out of whack temporarily. So, a lot of people when they do fast, they're supplementing with, sodium is the big one, just to make sure that your electrolyte composition stay in line. But, yeah, you're absolutely right. That in-between state, I'm not quite burning glucose, my glucose is dropping, but I haven't switched over to the ketone metabolism. Definitely, people struggle in that transition.

Melanie Avalon: This is so fascinating. I'm just wondering if there could be a point where people maybe are just perpetually in this state and never quite switching over?

Trey Suntrup: Yeah, absolutely. In fact, I've had that experience myself and the founder. I have had this conversation before when measuring ketones with our own device. We've got a group who loves to experiment, so we're always trying these little experiments in measuring our ketones, and I'm sure we'll talk about the device later. But the nice thing is you can take as many measurements as you want during the day, so you can really do these fun experiments where you're just tracking yourself every hour, for example, and really getting a sense of what's happening. And something we both noticed is that when we have our low ketone numbers, and then we have our high ketone numbers, and then there are these in between numbers. And we always feel the worse in that in-between state. Both of us have arrived at that independently, and one day we were having a conversation, we were like, “Oh, me, too.” It's really that transition that can be a little bit uncomfortable.

Melanie Avalon: I'm getting so excited by all of this, just by the potential and the benefit that a person could have by having the ability to measure their ketones for everything that we just discussed. A lot of follow-up questions to that, but I want to get a little bit more clarity for listeners about the different type of ketones and how they're generated and all of that, so they can get a good sense of what is going on. Because I know there's like three different type of ketones, I believe. Would you like to tell listeners a little bit about the different types and where they're found, be it the urine, the blood, or the breath?

Trey Suntrup: Sure, no problem. Ketones are produced in your liver. The first ketone to pop out of that process is called acetoacetate. Acetoacetate, the first ketone to form in your liver, that can be converted via enzymes into beta-hydroxybutyrate, which is the second ketone. Both of those ketones, after they're produced in the liver, are then released into the bloodstream. So, they're both circulating in your bloodstream. The BHB, the beta-hydroxybutyrate, is the molecule that is measured in a blood test. If any of your listeners are familiar, you've got these finger prick and test strip systems. They're similar to blood glucose systems. In fact, most of those meters are both blood glucose meters and blood ketone meters. You get a drop of blood, you hold it up to the test strip and a reaction takes place and it tells you what your blood ketone values are. That is a beta-hydroxybutyrate, we shortened it to BHB, because that's a bit of a mouthful. A BHB sensitive test.

The acetoacetate that is circulating in your blood along with the BHB is actually unstable. It's chemically unstable. What happens is that just spontaneously, that acetoacetate can degrade into acetone. And acetone is the third ketone. So, because acetone is a small molecule and it's volatile, it can actually diffuse into the airways of the lungs and then be exhaled in the breath. So, breath tests are really sensitive to the acetone. The acetoacetate that doesn't degrade into acetone, which hasn't happened yet-- Like I said, the reaction is spontaneous. So, you can think of it as random. Some of that acetoacetate is not going to turn into acetone, that can be filtered by your kidneys and then excreted in your urine. And the urinary test strips are sensitive to that excreted acetoacetate.

Melanie Avalon: Okay. I want to go through this and make sure I'm understanding and get some clarification.

Trey Suntrup: Yeah, sorry, that was a lot of information. [laughs]

Melanie Avalon: Oh, no, it's good. I just want to make sure I'm on the same page because I actually have some questions about what you just said, versus the way I was thinking it “went down.” When you enter the ketogenic state-- acetoacetate, the first thing that's created, is that converted into either acetone or BHB? Or, is BHB created independent of acetoacetate?

Trey Suntrup: Both the BHB and the acetone are initially derived from the acetoacetate. The way I think about, is that acetoacetate is like the parent ketone, and then it gives birth to these other two. That's kind of my silly analogy.

Melanie Avalon: Okay, I love that. I'm going to keep going on this a little bit longer, because I've been wanting to understand this for so long. This is like a lesson for me. We create acetoacetate, the parent ketone, and then you said it's unstable. Is that the reason that it becomes acetone or BHB, or does only the unstable form become acetone?

Trey Suntrup: Yeah, so I should clear something up here. So, the conversion between acetoacetate and BHB only takes place within the cells. That does not take place in the bloodstream, I should have mentioned that. Because that's enzymatic, there's an enzyme that has to catalyze that reaction, that enzyme is only found inside the cells. This is actually a point of confusion that I had for a long time that once I understood, cleared a lot of things up for me. Once the conversion of acetoacetate to BHB happens, and both of those are released into the bloodstream, while they're circulating in the bloodstream, the only thing that happens there is that the acetoacetate becomes acetone.

Melanie Avalon: I'm going to go through it again. When you say in the cells, I'm assuming that includes liver cells?

Trey Suntrup: Yeah, correct. Liver cells and peripheral cells, because the other part of this that we-- maybe this will help. The other part of this that we didn't talk about is that these ketones are circulating in the blood, eventually, they're taken up by the peripheral cells that are actually trying to use them for energy. Let's say, you have some muscle cells or you have some brain cells, will then take the ketones out of the bloodstream, and then use those for metabolism in a similar or analogous way to the way that it would use glucose, but a little different.

Melanie Avalon: Starting at the liver again. Acetoacetate is in the liver cells, and then it can be converted into BHB as well. And acetoacetate and BHB from the liver cells can enter the bloodstream. Stop me if I get it wrong at any point.

Trey Suntrup: No, you're good so far.

Melanie Avalon: Okay. So, then we have acetoacetate and BHB floating around in the bloodstream. Other cells can directly take up BHB, or they could take up the acetoacetate as well and convert it into BHB. Then in addition, the acetoacetate in the bloodstream could degrade into acetone.

Trey Suntrup: Yep, all that is great. Just one more addition, once in the peripheral cells, so let's say your muscle cells, the BHB that's going to be used for metabolism then has to reconvert itself into acetoacetate inside the peripheral cells because acetoacetate is actually the thing that's directly metallic So, that's actually the ketone that your body uses that enters the cycle to produce energy, to produce ATP. If there is BHB, let's say in your muscle cell, it has to convert first into acetoacetate inside the cell again before it can be used for metabolism.

Melanie Avalon: Sometimes, does acetoacetate get converted to BHB in the liver, go into the bloodstream as BHB, get grabbed as BHB and then converted back into acetoacetate in the cell?

Trey Suntrup: Yes, that can absolutely happen. Maybe your next question is why even bother?

Melanie Avalon: Yes. [laughs] Why?

Trey Suntrup: Right. Because it goes in one direction in the liver and then the opposite direction in the peripheral cells. The truth is, we don't quite know, but our best guess is that because BHB is stable in the bloodstream, that the body does-- well, there may be two reasons, but I'll talk about the first one now. Since the BHB is stable in the blood and the acetoacetate isn't, because the acetoacetate at any moment can just become acetone and acetone has very little metabolic utility by your body-- I think it can be used a little bit, but it's pretty much negligible from the perspective of helping your body generate energy. So, you can think of acetone as not useful for the body metabolically speaking. If the body converts the acetoacetate into BHB before it goes into the bloodstream, well, now the BHB is safe, that's not going to degrade into anything. One hypothesis is that this is a preservation mechanism actually that your body does to make sure that it doesn't lose the ketones to this acetone degradation.

Melanie Avalon: To clarify, you're saying that when BHB is taken up from the bloodstream into peripheral cells, it's actually converted back into acetoacetate?

Trey Suntrup: Yeah. There's a ratio of how much of it gets converted and we can talk about that a little bit later if you're interested, like what determines that ratio. But yes.

Melanie Avalon: Okay, because it's just so interesting because the vernacular surrounding BHB is that it is the fuel, but it's sounding it's actually the acetoacetate and BHB is the stable thing it's converted into before it's used as fuel.

Trey Suntrup: That's exactly right. In terms of metabolism, acetoacetate is the thing that's directly metabolized. BHB has other properties related to signaling. I don't know a ton about this, to be honest, but I do know that BHB plays an important signaling role for certain anti-inflammatory pathways. BHB has ancillary benefits outside of just providing an energy substrate for metabolism. But as far as the substrate that the body is using to make energy, that's acetoacetate.

Melanie Avalon: Can I just say how much I'm enjoying this conversation and learning so much right now? Okay, so with that whole understanding, I think when people first start a ketogenic diet, for example, are interested in gauging ketosis, they often try urinary test strips first to measure their-- I guess now I've learned, their acetoacetate. Which makes sense because you were saying how when a person is starting to enter fat-burning mode and a ketogenic state that acetoacetate is that big ketogenic currency that's being created first and then we're getting BHB, acetone. So confusing. But as far as the acetoacetate spilling over into the urine and measuring ketones with urinary strips, on a timeline for an individual, are they going to be excreting more urinary ketones when they first start a ketogenic diet? How revealing is measuring urine, for example, for ketones?

Trey Suntrup: I do think you're right. A lot of people do start measuring urinary ketones at the beginning of an experiment, for example, going on the ketogenic diet, because I think there's a lot of aversion to pricking your finger for a lot of people. If you're not a diabetic, you're not used to it. That idea just doesn't really sit right with most people. Actually, even diabetics now, as an aside, now that continuous glucose monitors are becoming more popular, you're even starting to see a shift within the diabetic community of not wanting to prick their finger. So, people understandably take a noninvasive approach and say, “I'm going to test my urine.”

The important thing to understand about urinary test, there's a couple different things actually to understand about them. The first is that because they're being removed from the bloodstream and then excreted in the urine, by definition, those are unused ketones. I think of them as like excess ketones in the sense that your body is not using them because they're coming out in your urine. So, that's the first thing.

The second is that for urinary test strips, they're really semiquantitative. They really only give you a range of concentrations. If you're trying to get an idea like, “Am I in ketosis yet or not?”, they can be useful for that. But they're really not going to give you a quantitative sense of the ketone levels in your body.

the third thing is because they're just sitting in your urine, the number that you actually see or the range, I should say, that shows up on your urinary test strip is going to depend on a couple of different factors like the level of your hydration or how long the urine has actually been sitting in the bladder, things like that. There are a couple different things that make it a little bit hard to interpret. But it's an easier test to do and it's more palatable for a lot of people than a blood test.

Melanie Avalon: Quick question, because a lot of people I feel when they are measuring urine ketones, for example, when they first start a ketogenic diet, oftentimes they'll find that, at the beginning, they start measuring high ketones and then it seems to go down. Would that be because what you just said? When they first started, they're creating a lot of acetoacetate, but they're not necessarily using all of it. And that acetoacetate is literally just going into the urine. But then as they become more “fat-adapted” or more metabolically efficient with ketosis, more of that acetoacetate gets converted into BHB instead of being wasted, is that a reason that their urinary ketones might start dropping?

Trey Suntrup: That's basically right. I think what happens is that your body becomes better calibrated to using ketones for fuel. What that means is it's just more efficient with its energy use. Part of that is actually downregulating the pathways that let the acetoacetate out into urine, your body realizes like, “Oh, this is what I'm using now for energy, I better hang on to this.” It just stops or it decreases the amount that's actually secreted in your urine.

You asked before about the timeline for that. I do think it depends, as all things with the human body, on a lot of different factors, and it's certainly personal, individual to individual, but a lot of people report along the lines of several weeks of being ketogenic before they start to see their urinary ketones drop. But it could be longer than that, depending on exactly what kind of diet you're following.

Melanie Avalon: Okay, gotcha. Maybe because I haven't asked you yet about the actual trials that you did in work with creating Biosense, but maybe that comes up with all this as well. So, moving beyond the urinary test for ketones, what determines, A, how much the liver creates BHB from acetoacetate and then that's in the blood compared to acetoacetate becoming acetone to be measured in the breath? Do those correlate? Is it like half and half, becomes half BHB, half acetone, or how does that work?

Trey Suntrup: Yeah, it's a great question. It's complicated by the fact that the answer changes depending on your overall ketone level and whether you're keto-adapted. We can say a couple things for sure, which is that the ratio of BHB to acetoacetate that is released into your bloodstream is controlled by what's called the redox potential of your mitochondria. This is the ratio of NADH to NAD+ in your mitochondria because that's part of the reaction that converts one into the other. NAD+, NADH redox potential is really what determines the ratio.

Melanie Avalon: Is there more beneficial side to that ratio, do we want more BHB versus acetone?

Trey Suntrup: Not necessarily. But there is some research now to suggest optimal ratios for your redox potential. I'm not super well versed in that research, but there are a lot of interesting longevity studies. I'm sure plenty of your listeners know much more about this than I do. But there are longevity studies out there that suggest that having certain redox potentials or certain ratios of NAD+ to NADH is beneficial for longevity because that ratio determines the ratio of BHB to acetoacetate. Maybe you can say that there's optimal ratio of those two for health, but really, it's about the redox potential, the mitochondria and those implications for health and longevity.

Melanie Avalon: I feel this is a David Sinclair question if I bring him back on the podcast.

Trey Suntrup: Yeah, there are many, many people out there that know much more than I do about this, but that's just a teaser.

Melanie Avalon: Yeah, teaser, to-do list. I interrupted you, what were you going to say next?

Trey Suntrup: Oh, sure. But then as the concentrations increase, sometimes the ratio can change a little bit. The ratio can also change if you are long term keto-adapted. We've seen this as well and some of our users who are measuring-- they're just super interested biohacker types, and they're measuring their blood and their breath at the same time and they have an idea for the ratio of their blood and their breath and they're seeing something different. A lot of times, it's because of exactly what you say, which is the ratio of BHB to acetoacetate can change as you become long term keto-adapted to.

Melanie Avalon: To that point, as far as the comparison between the blood and the breath and what that indicates, would that mean that it's not so much important for an individual comparing the blood to the breath as it would be looking at the breath over time compared to the blood over time? Because I know like a big question people have is, is measuring breath accurate? For some reason, there's this idea-- or maybe it's for good reason, maybe you can speak to this. There's this idea that measuring blood is the “gold standard,” that it's the most stable thing to measure or the most telling thing. I'm assuming you guys have found perhaps some evidence to question that a little bit since you have your device measuring the breath. So, yeah, what is the value in measuring the breath? How does it correlate to a person's state of ketosis? What might it indicate about how their body's running on ketones? What can they learn from measuring the breath?

Trey Suntrup: That's another great question. I'll answer it in steps. I think it's probably the best way. The first thing is to say that these old breath acetone devices really have earned their bad reputation, I'm sorry to say. It's not anything against anyone who's tried to develop one. It's actually that detecting acetone in the breath is hard. This is hard to do. We're talking about parts per million concentration of acetone in your breath, so we're pulling out one in a million particles in your breath and then measuring that. That's hard to do.

Historically, the way that breath acetone was measured was actually with these huge laboratory tools. Somebody would breathe into a bag, and then they would take it to this mass spec tool, and they would measure breath acetone that way because those tools are really set up to measure very low concentrations of things. Imagine that we're trying to pull a faint signal out of the overall signal here. That's the first thing to mention.

The second thing is that where our device, Biosense, is really revolutionary with respect to taking an accurate breath measurement is, we're using a deep long sampling process. What this means is that actually the concentration of any analyte that you would be exhaling, but in our case, it's acetone, is actually highest at the end of your breath. This actually makes sense if you start to think about it. If you take an inhale of air, a lot of that air is going to just sit in the middle of your lungs and not interact with your lung tissue because by the time that you exhale, it hasn't had the chance to migrate over to your lungs and have an exchange with your lungs. The first part of that exhale is mostly just the same ambient air that you inhaled in the first place.

Melanie Avalon: Unless you're like a yogi or something, constantly doing deep, deep breathing exercises.

[laughter]

Trey Suntrup: I have not thought of that, but that's true. It's a slightly different phenotype than what I'm thinking.

Melanie Avalon: But, yeah, no. 100%.

Trey Suntrup: Yeah. What our device does and what our intellectual property and our patent is about is, it is about having a device that you just breathe into essentially normally, and the device just ignores that first part of your breath. So, it just sits there and listens to you exhale. Once it determines that like, okay, they're running out of air, they're getting toward the end of their breath, then the device really kicks on. A pump inside the device pulls that last part of your breath from the device mouthpiece into the guts of the device and into contact with the sensor, and then the breath acetone concentration is determined by the sensor there. It's really this end-of-breath sampling process that really no one else does on any other breath analyte that really enables accurate breath measurements that have this nice correlation with blood measurements that has not existed before.

Melanie Avalon: When you're using the device, is there a countdown that you're supposed to follow? Or does it adjust to you based on however long you exhale?

Trey Suntrup: Yeah, it's actually personalized to the type of exhale that you have. Some people have really big lungs like me, I'm a bigger person. I once had a chest x-ray and the technician had to reshoot it because they didn't get on all lung in the x-ray, and they're like, “Holy cow.” I just have these very big lungs, so my exhales are very long. Other people, probably not so much. The device has a microphone inside of it that listens to the pattern of your exhale and just takes into account those different types of breathing patterns. Because the other thing you don't want to have to do with these devices, is all breath devices are going to have a technique to them to a degree, but what you want to do is to try to take out some of that variability so that it's not this tiny little Goldilocks zone of, “Hey, you need to breathe like this, but not quite like this and a little bit more like this.” Because for users, that's going to be frustrating if it's a complicated maneuver that you have to perform to get a measurement. Really what we're trying to do is replace an inconvenient measurement, which is a blood measurement where you have all these supplies and you have to draw blood, etc., with a convenient one. If the breath sampling process gets too complicated, then it compromises that convenience.

That's a long way of saying the device is really intended to account for those differences and that variability in the way that you might exhale.

Melanie Avalon: Some more actually quick follow-up questions while we're still talking about the acetones excrete it in the breath. How does that tend to correlate to BHB for a person? Does it tend to correlate? Or is it wildly different based on the individual?

Trey Suntrup: Let's talk about the historical studies first. There's actually not a ton of historical data on this. There are a handful of studies and the total number of data points that are comparing breath acetone. Remember, we're talking about breath acetone compared to blood BHB because that's what the two things that people may be considering measuring are those two molecules. So, the total number of data points comparing those two and the historical literature is something like 500 data points, which is actually very small. Most of those data are once-a-day measurement. Somebody who's fasting, they wake up and take a blood measurement, take a breath measurement, and then don't do it again for 24 hours.

What those studies tend to find is that the correlation between breath acetone and blood BHB is somewhere in the range of 0.6, there's an R-square to 0.6. A perfect correlation would be 1, a bad correlation would be down in the 0.2s, 0.3s type of range. You have this moderate correlation between the two. That's the historical data.

Now, we conducted a clinical trial this last fall, because we knew, exactly as you asked at the beginning, that most people are pretty distrustful of breath acetone devices up until now. We knew we're entering a space that maybe doesn't have the best reputation, we're going to have to hit the ground running with some clinical data so that we can really put our money where our mouth is. What we did in our trial, which I just brought up without you prompting me, [laughs] but we're going to get there, is we had 20 individuals walk around with our device and a blood meter, in our case. We use the Abbott Precision Xtra blood ketone meter because it performed the best in our validation studies, in our quality control studies. We had that blood meter and then our device. For two weeks, they blew into our device and pricked their finger at the same time five times a day.

These people are sitting down, these poor folks are sitting down with their blood meter five times a day and taking a measurement because we really wanted to also look at how people's ketones vary throughout a single day. I mentioned that that historical data, most of it is once--a-day measurements. So, it was really serving two purposes. It was how do people's ketones both blood and breath change during the course of a single day? And how do the individual measurements compare to each other? Does that make sense so far in terms of the study design?

Melanie Avalon: Yes, it does. It's interesting, because I had read some historical literature comparing blood to breath. What I had read was saying that actually it was pretty good, that it lined up pretty well, but I hadn't considered what you just said that that's probably just measuring one time during the day for each other, and the importance would be how is it changing throughout the day and constantly, so, yes, very valuable.

Trey Suntrup: Sure. For any one of those studies, the correlations will move around. Some of them have in the 0.8s, or I think there may be one is even as high as 0.9.

Melanie Avalon: The ones I read was 0.8 or 0.9, which I actually found really interesting.

Trey Suntrup: Right. What I did to arrive at my 0.6 number is I actually did a weighted average-- and this is a little bit sloppy, but it's good enough for now, is a weighted average of, how many data points were used to generate that correlation. I would weigh each correlation number from the literature by the number of data points that was used to generate it. If you had a study with 100 data points, that correlation would get weighed more than a study with 10 data points. When I say 0.6, I'm talking about a weighted average.

Let's talk about the results a little bit. When we did the multiple daily measurements, we found that people's ketones actually vary a lot during the day. I should mention that these folks that we had in the study were not diabetic. We had one diabetic, but they were not insulin dependent. But everybody else was a more or less metabolically healthy individual who was just interested in the ketogenic diet, interested in fasting, mostly for lifestyle reasons. Maybe they were the biohacker types. Those types of folks. They all essentially knew what they were doing and knew how to elevate their ketones. We didn't really provide any guidance on how to do that. We just released them into the wild and said, “Try to get your ketones up and take all these measurements.”

The first thing we found is quite a bit of variability even over the course of a day. The average, I think-- there's a histogram in our preprint, the paper that we're publishing on this, but the variation is about 50% on average for your ketones over the course of just a single day. We were able to really map out--

Melanie Avalon: And this is breath ketones?

Trey Suntrup: It's actually both. Both the blood and the breath came out to be about 50%.

Melanie Avalon: So when you did the test, you had them do both?

Trey Suntrup: Yeah, exactly. There's a measurement session where you would sit down and within a window of five minutes, take a breath measurement, take a blood measurement. You can actually get the traces of blood ketones throughout the day and breath ketones throughout the day and just set those right next to each other and start to look at the patterns, which was super interesting. There are a couple of those traces in the preprint that I mentioned that maybe we can link somehow.

So, that's the first thing is that there's quite a bit of variability both in blood and breath. The correlation that we found between the two, just a point by point correlation, was similar to the literature. I think ours was around 0.6 as well. In fact, I know it was. It was around 0.6, for the point by point correlation. But when you start to look at the traces next to each other, the blood and the breath, you notice this really interesting phenomenon where they're actually often offset from each other in time. Your blood ketones, let's say, they're going to rise from 0.3 millimolar to 1 over the course of a couple of hours, you'll see that happen in the blood. And then a little bit later, you'll see the exact same rise happen in the breath. So, there's often a delay between changes in blood and changes in breath.

If you imagine doing correlations between these-- you can imagine that that's going to affect your correlation. You're comparing a blood point that has popped up from baseline, but the breath hasn't risen yet. Those are going to look uncorrelated. When in fact what's really going on there is it's going to rise and correlate later, but just not quite at the same time.

Melanie Avalon: So, is that occurring because the acetoacetate and BHB is being generated in the liver, put into the bloodstream, it's in the bloodstream, and then a little bit down the road, the acetoacetate is turning into acetone, or is it not that simple?

Trey Suntrup: No, you're right. You're thinking about it exactly the right way. You can explain the delay with those processes exactly in the way that you mentioned. If you imagine the acetoacetate getting converted into BHB in the liver, you'd see BHB rise in your blood more than you would see breath acetone rise because the breath acetone comes from the acetoacetate, and what we're assuming is that all the acetoacetate or a lot of it has converted into BHB in the liver. That's the original state of things, that's going to cause your BHB to rise, but not your breath acetone to rise. As this production continues in the liver, eventually you're going to use up the redox potential and the liver is going to change or you're going to use up all the converting enzyme in your liver. And you're going to stop doing that conversion of acetoacetate to BHB because you just run out of the elements that you need to do that conversion.

At that point, you're going to have more acetoacetate released into the blood than BHB, which is going to show up as more breath acetone as the acetoacetate degrades. There are all these interesting dynamics in terms of the conversion rates of the ketones into each other, and the time it takes to do those conversions, the rate of those reactions, all those things conspire to give you this delay between changes in blood and changes in breath.

Melanie Avalon: Can I retell the story again and see if I'm following? I just want to make sure I'm following. From the liver can come BHB and acetoacetate, but probably in the beginning, there's more BHB coming out than acetoacetate. You spoke about the redox potential changing or the enzymatic processes being used, then maybe there's more acetoacetate coming out of the liver and not as much BHB. When the acetone is formed and excreted in the breath, does that occur in the bloodstream or the liver?

Trey Suntrup: Yeah, the best way to think about it is that the degradation of the acetoacetate into acetone, generally speaking, is happening in the blood. Think of breath acetone is just a proxy measurement for the acetoacetate that's in your blood. There's some percentage of the acetoacetate that's going to become acetone, and that's what we're going to measure. The easiest way when you're thinking through the three ketones as like a first-order approximation and simplification of the problem, is just to assume that the breath acetone is a direct proxy for the acetoacetate. And actually, something that helps a lot is in the paper, which we can link in the show notes. There is a diagram of this which makes it way easier to wrap your head around. I think it's figure 1 in the paper, I want to say. Yeah, so figure 1 in the paper has all these processes outlined in graphical format. It's just much easier to understand than trying to describe in words. When you hear all these molecule names thrown around, and this is converting into this and degrading into this, it can be definitely twist you in knots a little bit mentally. I do think it helps to get the graphical representation.

Melanie Avalon: For listeners, the show notes will be at melanieavalon.com/ketones, I will put a link to that study there so you can look at that graph.

Trey Suntrup: The last thing that we learned in the trial-- we mentioned the point by point correlation between BHB and breath acetone being around 0.6, and that correlation being, in large part due to this time shift and this time delay between the two ketones. Something that we can do is we can actually, instead of looking at the point by point correlation, we can look at the correlation between total ketone exposure during a single day. This idea is actually borrowed from drug development where they look at the clearing properties and the pharmacokinetics of a drug by essentially injecting the drug and then monitoring the concentration of that, whatever the molecule is, in your bloodstream over time, and they can track how quickly your body is able to clear the drug.

Ketones are obviously not a drug, they're a natural molecule that occurs in your body, but we can do something similar. We can look at measuring your ketones four, five, six, however many times per day, and then look at the area under the curve from that ketone trace to approximate the dose of ketones or the total amount of ketones that your body has seen that day. It's really a cumulative exposure metric. We mentioned earlier about the variability. Because your ketones are changing quite a bit throughout the day, looking at this really captures all that variability and all that behavior in a single daily metric, the daily ketone exposure, or we call it the Ketone Score in the app.

When you compare that daily exposure between blood and breath, the correlation is 0.83. So, much higher. What this means is that if you were to take five measurements per day with a blood meter, which we would suggest that you need to do to capture all the variability that we discussed earlier, that 50% variability, and then you were to take five measurements with a breath device, the cumulative result of those two are going to be very highly correlated.

Melanie Avalon: You're saying in the app, does it give you a score of that cumulative amount?

Trey Suntrup: Yes, it does. That amount is going to accumulate throughout the day. Each time you take a measurement, it's going to add a little bit to that score, that area under your curve, that ketone score. At the end of your day, you can really get a sense of, again, the exposure that your body's had to ketones that day, the total exposure. It's going to take into account all that variability, how high or low your ketones were that day.

Melanie Avalon: Does that require a minimum amount of measures to guess that because if you only took like one measurement--

Trey Suntrup: Right. Yeah, we did this analysis with our clinical data, and what we found is the best tradeoff between number of measurements-- because some people like to take 20 measurements, but we don't want to insist on that. The minimum number to really get you reasonably close in terms of accuracy is three. We really recommend about three measurements per day. The more you take, the more accurate that score is going to be. But you can get reasonably close with three measurements, morning, afternoon, and evening measurement.

Melanie Avalon: Did you guys ever do any tests with people taking in exogenous ketones like MCT oil?

Trey Suntrup: MCT is interesting. We have actually done that. We've done that with the internal team and we've had some folks, some of our users do that too. With MCT, you will see a spike in your breath acetone. Yeah, that's just the fact of it. If you're talking about exogenous ketones like exogenous BHB, like a ketone salt or a ketone ester, that's a little different. We have less experience with that. And because you're taking a BHB ester or BHB salt typically, that's going to spike your BHB immediately, so you'll see that in your blood. The change in breath acetone is going to occur sometime later for the exact reasons that we've already discussed. These processes that convert one ketone into another are going to take some time. You probably will see a bump in your breath acetone sometime later. But as far as the exogenous BHB, that's really going to spike your blood BHB specifically.

Now, there are some research groups who are developing-- or have developed these diesters or acetoacetate exogenous ketones. We have not had anyone test those with a breath acetone device, but that's actually something we'd be really interested in is actually-- if you were to take exogenous acetoacetate, you would probably expect to see a faster spike in your breath acetone.

Melanie Avalon: Okay, that's fascinating. I'm just having a major epiphany right now, because I know this is totally [unintelligible [00:48:28] one but I know for me, I've gone through periods of doing a very low-carb high MCT oil diet. And I always found that when I would bring in carbs, I would immediately start-- at least intuitively seem to excrete ketones through my breath. I wonder if that was because it was switching over from using the acetoacetate as potentially fuel in the cells and then switching it over to excrete it as acetone.

Trey Suntrup: Oh, interesting. We have users write into us all the time with those types of experiments. And it's been so fun to learn along with our users. Because we’ll sometimes sit there and develop a little bit of a back and forth and be like, “I wonder if this is what's going on," or what-- It's really this communal learning experiment that we're all going through. And that part has been a lot of fun.

Melanie Avalon: So fascinating. I feel like I'm going to have a gain day experiments, especially like the MCT oil and everything. Random question, correct me if I'm wrong, but I had read that acetone, which we're measuring of the breath, but which we just said we could sort of see it as like a gauge of a acetoacetate but the acetone itself is not used as a fuel.

Trey Suntrup: Correct.

Melanie Avalon: Would that mean if somebody for some reason, based on their enzymatic processes, if they're generating more acetoacetate and less BHB, and I don't know how big the variance is between individuals, but if that's the case, would they possibly be the type that wouldn't as easily gain weight on a ketogenic diet because more of the ketones are more likely to be excreted rather than used as fuel? I don't know if you can make any connections or associations there, but I'm just wondering weight gain, the ability to turn ketones into fuel versus just excluding them.

Trey Suntrup: Yeah, I'm actually not sure about that. I will say that we discussed before that once your body becomes adapted, it stops or at least decreases the amount of ketones that it's excreting in the urine. If you've been at it for a while, then your body essentially figures out-- it titrates the amount of ketones it's producing versus it's using and gets itself into a more calibrated state than when you first start. I'm not sure what the implications would be for weight gain though.

Melanie Avalon: What sparked me to think about that was I was actually listening to a Peter Attia podcast episode recently. For listeners, I'll put a link to it in the show notes. They actually were talking about you guys very favorably. They were talking about measuring ketones and all the implications and the difference between measuring blood versus breath. They were saying-- I was really happy because I know I was bringing you guys on, and I was listening to it. And they start talking about you and I was like, “Oh, I hope we're in favor here with this company.”

[laughter]

Melanie Avalon: Because I really respect Peter Attia. They were actually very much in support of Biosense. They were saying that it did tend to correlate pretty well to measuring blood ketones and that it was way less invasive, so that it was very, very practical to use it, compared to people who don't want to be pricking themselves every day. But something that was really, really interesting. I don't remember who was being interviewed, but I will put a link to it in the show notes, but one of the things that they mentioned was that, I think there was three people on the interview. But one of the guys was saying that breath acetone was actually more likely to come from body fat. Do you have any idea why that might be? Now I'm just trying to think about why that might be.

Trey Suntrup: No, I don't, but if you're citing folks on that show, you're probably on reasonably solid ground. But I would love to know, along with your users, if you can find a reference to that and post it, I would love to listen to that.

Melanie Avalon: I'll circle back with more information. Yeah, the notes I'd taken from it was that they had found that breath acetone was more likely to come from body fat. They said they found that exercise tended to lower breath acetone and BHB. But then after exercise, after a period of rest, the breath acetone started to go up again.

Trey Suntrup: Yeah. There are a couple of different reasons why we see that. We also see that. You get this temporary dip a lot of the time. This is particularly the case when your ketones are elevated before you exercise. If you go into exercising and your ketones are up after you exercise, they dip a little bit and then they shoot back up. There are a couple different reasons why this is probably happening.

The first is that when your ketones are elevated in the first place, that means your body is using them for fuel. They're using them as this metabolic substrate. Part of what happens during exercise is you're actually just using the ketones that are in your body, so they drop a little bit. The other reason is because when you exercise, you release stress hormones, which tend to cause a temporary spike in your blood glucose as well. You get this little spike in blood glucose, which type 1 diabetics are very familiar with if they like to exercise. That little spike in blood glucose can also downregulate your ketone production temporarily. It's probably a combination of both of those to varying degrees. But yeah, that pattern of immediate dip after exercise and then rising back up is something that we see pretty frequently.

Melanie Avalon: Okay, actually, you just tapped into two huge things I wanted to jump into. I'm glad you brought that up. I do want to circle back. I mentioned the Lumen device at the beginning, because I did recently have the founders of Lumen on the show and they also have a breath device for listeners who aren't familiar. Their device, it doesn't measure ketones at all, it actually measures the ratio of oxygen to carbon dioxide in the breath to evaluate if you're generating energy from glucose or carbs compared to generating energy from fat, so it's not measuring ketones. I found it really, really cool and very, very valuable. I'd love to hear a little bit-- because I'm all about having as many tools in the toolbox that you can have and learning as much as you can about yourself and what works for you.

Say, for example, a person does have a Lumen device and they're measuring their breath to see if they're in “carb” or “fat-burning mode.” If they have a Biosense device and they're measuring their ketones, is there a correlation there? Is it most likely that when they're measuring-- because Lumen the way it measures is it measures 1 to 5 for fat to carb burning, and it's not actually measuring-- the device is not measuring 1, 2, 3, 4, 5. They said their data is actually much more expansive than that but that's how they chose to qualify it through the software. But would it be reasonable to state that if a person is measuring “fat burning” on the Lumen, that they're probably going to be measuring ketones on the Biosense? And then beyond that, say they're measuring one fat burning on the Lumen, is it most likely with the Biosense that they might measure much more nuanced or much more larger range of “fat burning” because there's a range of ketone burning? I don't know if I ask that right.

Trey Suntrup: No, Yeah, you did. That's great.

Melanie Avalon: Many of my listeners have Lumens, so they're probably going to be like, “Why would I want to measure ketones if I know that I'm fat burning?” What would be the value in actually being able to measure both?

Trey Suntrup: Yeah, the Lumen device is measuring a variant or an approximation of respiratory exchange ratio, which like you said, is the ratio of inhaled O2 to exhaled CO2. That can give you an indication of, if your body is burning all carbs or if it's starting to flip over into a fat-burning state. There is a study that actually directly compared the two measurements. That's another study that we can toss in the show notes too so that people can look at that. Essentially, what you notice is that as the respiratory exchange increases compared to breath acetone, pretty quickly, it flattens out. And what that means is that-- I'm thinking of a plot of this respiratory exchange ratio to the respiratory quotient to breath acetone. What that means is that as breath acetone continues to change and increase, the respiratory exchange ratio stops changing, it just flattens out and becomes constant.

The way that translates into ranges from their device to our device, is the full range of their device fits in about the first three units of our device. I actually haven't said anything about units, but our device measures breath acetone in units called aces. We can talk about exactly where those come from in a minute. But we have a range of 0 to 40 in increments of 1. The types of measurements that you get is a 5 or a 13, or a 33. You can get 40 different measurements on our device that tell you how many ketones you have. If you're looking at the full range of Lumen, that fits in about the 0 to 3 range of our device. So that's sort of a very, very low fat-burning range.

If you are a 3 on our devices, like very slightly elevated ketones, that's the first unit that we say is however so slightly elevated over your baseline, your baseline ketone level on our device is about 0 to 2. So, even if you're eating high carbs, you're going to be somewhere between 0 and 2, just because you have some background rate of ketone production, even when you're eating a lot of carbs. The first unit that's like a little bit elevated is a 3, and that's the top range of the Lumen.

Melanie Avalon: Okay, some clarifications here, just because this will be very specific to my audience specifically. I drew a little graph out when you're making those numbers. If a listener is measuring the carb versus the fat burning on the Lumen-- because you're saying that actually the 0 to 3 in the Biosense, that would actually correlate to the carb-burning on the Lumen, or would that 0 to 3 probably-- I mean, I know it's hard to know because you don't have their device and you don't know what the actual measurements are. But would it be more likely that that 0 to 3 is actually still-- in the fat burning up the Lumen, does that make sense?

Trey Suntrup: Yeah, it does. I'm not exactly sure how their units work, but I think the highest fat-burning state on their device is a 1. It actually goes in the reverse order.

Melanie Avalon: Yeah, they call 1 and 2 fat burning. Three, they call carb fat. Four is carb, five is carb.

Trey Suntrup: Got it. The highest fat-burning state for them is equivalent of a 3 on our device, which is very, very low levels of fat burn. In fact, a 3 on our device, you actually haven't transitioned into what's traditionally thought of as ketosis. You may be starting to burn fat, which is I think what that device is telling you, but you haven't transitioned into ketosis where you're deriving the majority of your energy from fatty acids and ketones. The highest range of fat burning on that device stops before you enter ketosis according to our device.

Melanie Avalon: Okay. Although actually, most likely if a person is in ketosis, it would plateau at 1 fpr Lumen?

Trey Suntrup: Exactly.

Melanie Avalon: For our listeners, if you had both devices, what it sounds like is-- say you're experimenting with different dietary choices, cycling between ketosis, fat burning, carb burning, the Lumen device will be telling you, when are you switching into fat burning, when are you switching back into carb-burning, what does that look like on that timeline. But then when you're actually in the fat-burning state, and you're wanting to get the nuances and really deep details of your ketones in the ketogenic state, now it's like you're expanding that fat-burning state 40 more units to see the level of variance in that fat-burning state as to how it pertains to ketones.

Trey Suntrup: Yeah, I think that's pretty accurate. The other reason why it's interesting, it's not just interesting to track the transition into ketosis because we were talking about that earlier and how that can be a little bit of a bummer. Above 3, you're going to start to see that transition into ketosis. Just for reference, that transition occurs around a 5 on our device, so a little bit higher state of fat burning. But also, if you're interested in the other ancillary effects of having ketones in your body, for example, the anti-inflammatory effects, those signaling effects tend to kick on a little bit higher. I think it's around a 10 on our device. So, 1 millimolar BHB or a 10 on our device is around when you start to get those signaling benefits.

So, if you're doing a fast and you're trying to get your ketones elevated a little bit more than just transitioning into ketosis and try to get them elevated above that, our device is really going to tell you with a high level of granularity, again, 40 units-- and I should also mention that the reason we're able to provide that level of granularity, again, goes back to this end-of-breath sampling that we're doing. Again, no one else is doing this sampling method on a breath device, but it really does enable that highly accurate, highly precise determination of the concentration of gas in your breath and allows us to be able to make statements like, you're a 31 instead of a 28. That's a very precise difference that we're resolving there.

Melanie Avalon: Gotcha. Do you find people practicing a one meal a day type situation, eating a lot of carbs in their eating window, do they tend to enter a ketogenic state in the next day's fast? Or does it vary wildly-- Do some people actually get deep into ketosis? Or does that actually take a lot of effort to get deeper and deeper?

Trey Suntrup: It really depends on what you're eating on your off meals. You've already put your finger on that in your question. Our founder likes to tell a story of one of his early testers of a prototype, who would do fasting during the day for religious reasons, but then at night would eat a bunch of rice, would just eat tons of rice with his meal. But then would fast from then until the next dinner. That person saw no ketones because they had built up their muscle glycogen store so much with all the rice that they were eating-- because this is actually another point that we haven't talked about yet. But you have to remember that before you start burning fat for fuel, you have to burn through your glycogen first, your muscle glycogen depending on how big you are, but there's quite a lot of it and it can provide energy for you for a day or so.

I can speak for myself with my own experiments. I did a super low-calorie experiment for a few days just to see if I could get myself into ketosis by restricting calories. I didn't even pay attention to carbs. I just did a low-calorie thing. And I did get into ketosis, I got into pretty good ketosis, but it took me a couple of days. Because that first day, I was really churning through my glycogen and so I hadn't started to tap into my fat yet.

To answer your question, depending on what you're eating on that meal before the fast, that's really going to determine how high your ketones get during the fast, but that's another reason why it's important to measure. Because if you're just doing time-based fasting and you're saying I'm going to fast for 12 hours or 16 hours or 24 hours, that's great. That's great as a general guideline. But you don't really know what's going on in your body unless you're measuring. What's going on in your body is going to depend a lot on what you do outside of the fast.

Melanie Avalon: This is a question that haunts me literally every single day. I wish I was joking. Liver glycogen, is that a hard stop on ketosis? Does it pretty much have to be depleted for ketosis to start?

Trey Suntrup: I saw this on your questionnaire, and I don't know the answer to that.

Melanie Avalon: Because I can't find the answer. I google it every day.

Trey Suntrup: Yeah, I'm totally not the person to ask.

Melanie Avalon: Okay. If you find somebody who knows the answer, let me know. The reason I'm asking is because people say it all the time. They're like once you deplete liver glycogen is when ketosis starts. But I can't find any studies that talk about it, really.

Trey Suntrup: My understanding of what happens, let's you're just fasting and you cut out all food. During the beginning of that, the first thing you're going to do is burn through the glucose that's in your bloodstream from the last meal that you ate. You're going to metabolize that. Then, you're going to tap into your muscle glycogen stores, and you're going to use that.

Melanie Avalon: I feel the muscle glycogen, isn't it spared though? I feel it's not really tapped into.

Trey Suntrup: What I've seen is that, when I did the low-calorie experiment that I just mentioned, that first day, I didn't have ketones, but I lost weight. I lost a couple pounds. Some of that was water, but I think some of that also was glycogen.

Melanie Avalon: From muscle?

Trey Suntrup: Like I said, I'm a big person, so I assume to lose enough, it would have to be my muscle glycogen.

Melanie Avalon: Yeah. I'm fascinated by glycogen. I want to have a glycogen episode.

Trey Suntrup: Well, it's funny that you mentioned that because interpreting ketone data-- when we get questions about what is going on with my ketones, more often than not, the answer involves glycogen. You have good intuition for it as being a super important element and trying to understand metabolism. We've had somebody say, “I did a 12-hour fast, and I'm not in ketosis yet. And I exercise too.” “I did a 12-hour fast, and I went on a long bike ride, and I'm still not in ketosis.” And the answer is that they were still burning through their glycogen. After the exercise, they would refeed and then they would refill their glycogen even more and they would just never see ketones. What they started to do was, do the fast, exercise, and then continue the fast, and then they would see their ketones go up.

Melanie Avalon: Gotcha. Two points what you just said. I think the reason I'm fascinated by it is for me, historically, for the longest time, I followed a low-carb diet with fasting. Yes, I lost weight, but once I actually switched to a high-carb, low-fat diet with fasting-- I was eating massive amounts of fruit at night, so I was definitely filling up liver glycogen completely, probably, every single night. I actually started losing more weight. The haunting question I had was, “Okay, while fasting, was I ever entering into ketosis or was I running off of liver glycogen?” I'm just very confused as to how-- the ketogenic process, how much is glycogen affected?

Trey Suntrup: Yeah, absolutely.

Melanie Avalon: It's fascinating. Then, the last thing was a lot of people have been using the Lumen device, and they've been reporting back, that there'll be like 25, 26, 27 hours into a fast and it's showing them at like a 4 carb burning. And now I'm like, you probably-- this would be really good time to have a Biosense device to see what's really going on as far as ketosis with all of that.

Trey Suntrup: Yeah. I should also mention, with respect to research, that's another thing that our company, Readout Health, is really interested in is research and supporting research activities. We're involved in several clinical trials at a couple of different academic institutions and have one planned in industry as well. And we're super interested in exploring some of these questions. You have to remember that until now, doing semi-continuous ketone measurements reliably was just not possible. You can start to imagine all kinds of interesting ideas for experiments and clinical research that we can do to try to answer questions like this. Of course, we're a company selling a device, but we have a deep interest in the scientific work that's going on in the space and how we might be able to support it.

Melanie Avalon: I love this so much. I personally have been a little bit, like I said, hesitant about measuring the breath, but when I spoke to you guys, I was so excited by all of the research and the science you're doing and then hearing, talked about in Peter Attia podcast and doing more research, I just think this is so valuable for people. I think this might actually be the key for me personally to figuring out-- because I feel recently I haven't been able to really tap into the ketogenic diet, despite everything-- something's just not clicking. I feel this might be a game-changer because I'm going to be able to really figure out what's happening to me, as far as ketosis goes.

Trey Suntrup: Sure. That's another reason why the high resolution that we have is so valuable for experimentation. Something that we haven't touched on yet is the importance of feedback when you're trying to make a dietary or lifestyle change. I make a decision, and then I get the feedback very quickly after that decision, an hour or two after. So, that's a much quicker cycle than a weight scale, for example, which first of all is going to fluctuate all over the place. Second of all, you can only really do once a day and even then, that's probably too frequent. But the idea of having that tight connection between the choices you're making and the outcome that you get is so important for understanding how your body is working and charting a path forward with the choices that you're making. And the high resolution of our device allows you to say, “Oh, that meal dropped me from a 25 to a 19. I have a sense now, a very precise idea of the effect of that decision on my metabolism."

Melanie Avalon: I am loving this so much because you guys sent me the device. Thank you so much. I actually haven't tried it yet because I wanted to have his conversations. Now, I'm so excited to get it open and see what I can learn. Really quick question, I know we're running out of time, does it sync up with an app?

Trey Suntrup: We have a free app that you can download on the App Store, Google or iOS. The data syncs over to the app via Bluetooth. The device can actually be used-- another advantage of our device, it can be used as a standalone device, because there's actually a screen on the device that tells you what your number is. The device can also store up to 100 measurements on its onboard memory. The founders, it was really important to them to remove as many barriers as possible, and they really didn't want to be in a situation where you always had to have a cell signal, where you always had to have the device in one hand and your phone in the other hand to take a measurement. That's why the onboard device screen is there and why it's so important to us. But at the same time, you can whenever you want, open up the app, and then just sync your data over. So, you don't have to do it after every measurement. You can, of course, if you want to. But if you want to take a whole day's worth of measurements, take five measurements and then go home and sync to the app at the end of the day, you can.

The app has the ability to track all of these trends on, of course, a daily basis, on a weekly basis, a monthly basis, and you can really start to see those trends. Something that we're about to release during the month of July that we're really excited about is the ability to add annotations and notes into your graph. If you want to say, I had a meal here or I went for a jog here, and then you can see those notes and annotations show up along with your ketones. You can really then start to draw that connection between what you're doing and the patterns that you're seeing in your ketones. That's not in the app right now, but we expect that that will be out sometime this month. So, we're super excited about that.

Melanie Avalon: Awesome. This is so incredible. My listeners, particularly, since a lot of our fasters, a lot of them play around with keto diets, are going to find so much value in finding out how they're responding to keto diets, how they're responding to fasting. This is just absolutely wonderful. For listeners, if you'd like to get your own Biosense device, thank you, you guys do have a wonderful offer for our listeners, you can go to mybiosense.com. If you use the coupon code, avalon20, you will actually get $20 off the device. So, that is incredible. I will put that information in the show notes.

Thank you so much, Trey. This has been absolutely incredible. This is the last question, I swear, I know we're out of time but the last question I ask every single guest on this podcast, and it's just because I've come to realize how important mindset is surrounding everything. What is something that you're grateful for?

Trey Suntrup: Oh, that's a great question. I actually took a vacation last weekend out to Sunny California. It was the first vacation that I had taken in almost a year, and I was so grateful to sit on the beach and just relax for a few days.

Melanie Avalon: What part did you go to?

Trey Suntrup: San Diego.

Melanie Avalon: Oh, I love San Diego.

Trey Suntrup: I do too.

Melanie Avalon: That's awesome. Well, thank you so much. I learned so much. This was just absolutely amazing. I'm so excited to start using the Biosense device and I know my audience is going to love it as well. Thank you. Maybe we can bring you back for part 2 after you guys have done more research because I could keep talking to you for like hours. This has been great.

Trey Suntrup: Anytime. I'd love to come back.

Melanie Avalon: All right, thank you so much.

Trey Suntrup: Thank you.

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