The Crazy New World Of Ketone Esters (& How To Use Ketones For Sleep, Performance, Recovery, Fat Loss, Plant Medicines & Much More) With Michael Brandt Of HVMN

On this episode of the Ben Greenfield.

Fitness Podcast, it goes back to that, like, ketones per dollar. Like, make ketones as available and accessible as possible so that all the good researchers can create new science.

It kind of seems similar to ketones. It's like if you can't have protein and can't eat a lot of calories or want to fast and not lose a lot of muscle, then ketones seem to actually allow for a little bit of that effect.

Stands to reason for a healthy human adult that you might be able to get a surplus of cognitive ability if you're taking a ketone.

Health, nutrition, longevity, ancestral living, biohacking, and much more. My name is Ben Greenfield. Welcome to the show. All right, folks. Well, I've talked about ketosis before on my show because I have been kind of like messing around with it for a long time. I guess since I was like 17 years old, which would have been 23 years ago, I was toying around with ketosis for bodybuilding and later got into ketosis and even drinking MCT oil from a hot water bottle that was totally nasty. And eventually consuming ketone esters for Iron Man, TR triathlon and for endurance sports. And I even remember one particularly riveting tough mudder I competed in where I took a giant shot of these things called exogenous ketones, in this case, these ketone esters that one of my friends who worked for this company, hvmn, sent to me. His name was Jeffrey Wu. And Jeffrey sent me some of these HVMN ketones, which frankly were similar to a lot of the other ketone esters that I consumed. Aside from the fact that they were liquid and taste a little bit better, I drank them, but I also consumed a bunch of sugar. I had a bunch of fructose and maltodextrin from a carbohydrate containing sports gel, which I theorized would amplify both my blood glucose levels and my blood ketone levels and serve as a sort of rocket fuel to make me feel really amazing. It actually did. Like, because I had a huge amount of fuel for my liver and my heart, my diaphragm in the form of ketones going through my body. Then I also had the mass amounts of blood glucose for glycolysis and fueling skeletal muscle contractions and kind of crushed that race. It was pretty good. But ever since all my experimentation with all this ketone stuff, things have gotten a little bit more trendy. I've witnessed a whole rise, a whole empire of ketone based cupcakes and muffins and smoothies and goodies and supplements and things have become also more cutting edge. There's great researchers, guys like my friend Dominique D. Agostino doing research on ketone esters, and even the folks at HD HVMN themselves. My friend Jeffrey Wu works in close conjunction with Michael Brandt, his co founder and CEO. Down there at hvmn, which stands for Health Via Modern Nutrition, they're pushing out a lot of really cool research on ketones and anybody who hasn't messed around with these things for their appetite satiation or their performance enhancing or their inflammation quelling effects should be looking into them. And so HVMN is one of those companies that launched the world's first ketone ester. Probably that one I tried back when I raced that Tough Mudder in 2017. They secured a pretty hefty contract with US Special Operations and have worked with a lot of first responders and elite athletes and military performers since to use ketone esters for performance and recovery and metabolic health and longevity. And in my opinion, one of the coolest aspects of them is you take a shot and you just like don't feel like eating for good six to eight hours afterwards, which is kind of a handy little productivity hack. So anyways, the reason that I wanted to record this podcast for you today is a I have Michael Brandt, the co founder and CEO of hbmn, on the call with me and B HVMN just launched a kind of unique form of ketone ester, the science of which we'll get into on the podcast today because it's pretty cool. It's called Ketone iq. So everything Michael and I talk about if you go to the show notes@bengreenfieldfitness.com ketone podcast that's bengreenfieldfitness.com KetonePodcast I'll put links not only to this new Ketone IQ stuff that HVMN is churning out, but also all the other podcasts and articles I've done about ketosis, et cetera. That was kind of a long introduction, so I'll shut up. Welcome to the show, Michael Hey Ben.

Thanks so much for having me and it's great to connect with a fellow endurance athlete. I'm A Besides running HVMN, I'm also a 242 marathoner, have run in the Boston Marathon, ran the Burning Man Ultra Marathon, and so definitely get after it. So good to connect on a few different levels here.

Wow. Thanks for having me on 242, dude. All you got to cut is 40 minutes and then soon you'll be competing with the best of them. No, seriously, that's pretty respectable. Anything under three hours is obviously respectable marathon time, so good job. Although I wouldn't classify myself as an endurance athlete much anymore, man, but my form of endurance is walking down to my mailbox and back these days.

Yeah, yeah, there's levels to the game and it's hard to, it's hard to maintain that peak Ironman level fitness.

I know.

Arguably not even a good idea if we're talking longevity to maintain that level of dialed in.

Yeah, there's some potential issues with arterial stiffness and endocrine function and some other problems that seem to pop up with ultra endurance sports. Although I think painting with a broad brush, you're still going to be healthier if you've done like 50 Ironman triathlons when you're 90 years old versus if you hadn't. But I, I feel like for me personally, I've just wanted to move on into other things in life. Though a lot of people still think I'm super duper hardcore into endurance sports. Like I had, I think it was a Navy seal, you know, like armed forces special operations kind of guy. Speaking of, of ketones and special forces, he emailed me a couple of weeks ago asking me if I wanted to do this big swim, bike run competition with him and his homies from around the world, traveling global hotspots and getting dumped out of planes and, you know, trekking through the wilderness with backpacks on and stuff. And I was like, yeah, probably. Probably not a hell yes for me these days. If you guys are going golfing, I might join in.

But sound, sounds fun though, to be honest, for where I'm at in life. That sounds like a, that sounds like a great day out. So.

Yeah, yeah. So these exogenous ketones, I mean, honestly, like the average intelligent person walking around nowadays knows that, you know, if you restrict carbohydrates, your body starts to make ketones to burn instead of the glucose that you'd normal get from the carbohydrates. Most people can wrap their heads around that concept. And I think a lot of other people are also aware that if you kind of shift too much into that state and your blood sugar levels are all willy nilly, such as would occur in the case of say like a diabetic who hadn't been able to administer insulin, they might shift into a super dangerous state called ketoacidosis, where your body's Just like bringing all troops out into the bloodstream to try and get you some energy. And so you have massive amounts of ketones and massive amounts of blood glucose. And that's kind of a deleterious state to be in. But that's an extremely rare case that would only occur with say a diabetic mismanaging insulin. And so those are probably the two forms of some element of ketosis that a lot of people are familiar with. But in terms of these exogenous ketones, like the ability to actually be able to shift yourself into a state that normally you'd have to attain through fasting, or an incredibly large amount of, say, McTool consumption or something like that. Can you explain to my audience just basically what an exogenous ketone is and the basic mechanism of action via which they're actually working? Like, what are these things and how are they working in the body?

Yeah, so you said it just right. The human body has always made ketones for 300,000 years. Always has, always will. Your body makes ketones when you're in a carb deprived state. And you can induce that with different dietary things. You can eat less carbs, you can eat more healthy fats. The real innovation that we have on our hands here is a, a directly drinkable ketone. So to give a sense of the frame of reference on it, you can do the keto diet or you can fast. I think a lot of your listeners have done multi day fast. I've done a seven day fast. I know you dabble around a lot in there. By directly drinking an exogenous ketone, you can get your ketone levels to the equivalent of what you would be at on day three or four of your fast in units.

Just so people know that's something. If you were to get a breath ketone monitor or blood ketone or something like that, it'll typically measure your levels of ketones is something called millimolars per liter. And if you've fasted the entire day and your body's somewhat used to fasting and used to burning fats, you might be at like maybe 2 to 3 millimolar, possibly a little bit higher. About the highest I've seen myself is in a fasted state with a whole bunch of ketones on board. Well engaged in hefty exercise. I it approached about six and a half for millimolars per liter of ketones. But generally it takes a long time. A lot of fat adaptation, a lot of carbohydrate restriction and a lot of supplementation to Shift yourself into that state. And so what you're saying is basically the use of exogenous ketones shift you into that state pretty readily, even if you're not, say, like a well versed, high fat, fasting type of person.

Yeah, it's like how fast does a cup of coffee hit you? It's immediate, it's 15 minutes. Your ketones start to rise, they'll peak in an hour or two. And then with what we have with our HVMN ketone iq, we'll keep you there for five, six hours.

Yeah, yeah. And by the way, something I wanted to ask you is let's say that you're somebody who actually is used to fasting, you've modulated your carbohydrate consumption for a certain period of time, maybe a few years, you're in relatively good shape, you exercise, etc. Etc. And perhaps you've even messed around with MCT oil or some form of ketone esters or ketosis in the past. When you consume a ketone ester, like this new ketone IQ stuff, or any other form of ketone ester, do you know if someone who falls into that category would actually see a more appreciable rise in their blood ketones compared to someone who wasn't really used to messing around with any of this stuff? Or is it kind of the same? No matter who you are, you'll see.

The same pharmacokinetics that you'll see see the same thing happen. However, your subjective response might be different and more of a, A factor that will change more is your ability, your body's ability to utilize and mobilize those ketones. So people who are more keto adapted tend to feel it more. Like, if you think about it this way, if you're, you've been around on the planet for 30, 40 years and you've always eaten a ton of carbs, you spent very little time in ketosis since you were a baby and you all of a sudden one day drink a ketone ester. Your body's not going to know what to do with it. It'll figure it out, but it's not going to have the enzymes ready to go and mobilize those.

Gotcha. So to clarify real quick, basically the evidence that you have a lot of ketones in your bloodstream, a high millimolar per liter value of ketones is not indicative of your ability to be able to utilize those ketones for energy.

Right. Because 50 grams of ketones is. 50 grams of ketones is 50 grams of ketones, it'll up your blood ketone level. And then the question is, how good is your body at knowing what to do with it?

Now, in terms of the actual utilization of ketones, the biochemistry of being able to take your high blood levels after you've consumed something like let's say this ketone IQ and you have elevated levels of ketone bodies, what would be the limiting factors in terms of your ability to be able to utilize them? Like if someone is fat adapted or used to being in a state of physiologic ketosis, what is it that allows that person to be able to utilize ketones more readily than somebody who might not be used to higher levels of trace ketones in the blood?

Yeah, there's this general concept of metabolic flexibility where if you're doing endurance training, if you're eating lower carb and you habitually have elevated ketone levels, your body builds up more enzymes that are able to utilize those, turning it into cellular ATP. So you just, you just have more, more of the necessary gearing to put that fuel to use.

So basically these ketone bodies that are produced, is it more of like an enzyme issue? I mean, obviously we know, for example, as, as we're going through the Krebs cycle and we take acetyl COA and push it through the Krebs cycle, that kind of midway through that Kreb cycle there is some beta hydroxybutyrate formed. And you know, in the formation of beta hydroxybutyrate and its subsequen, there's also utilization of NAD and the formation of nadh, which is also why NAD is so fantastic, I think, especially when paired with the use of ketones or ketotic based diet. But that aside, is there a certain enzyme that might be a limiting factor or a certain factor aside from ketones that you see upregulated in someone who might be a little bit more keto adapted, so to speak?

Yeah, there's a few different things. I'm hesitant to point to one specific one because metabolism is complicated. And what we've seen more at the ecological level is just that people clear out the ketones more quickly when they more often have ketones around in their system. The exact mechanism of action, like why exactly these are clearing out faster? Not entirely known, but we do see people use those ketones more quickly.

Okay, so basically what you're saying then is if someone were to supplement with a ketone ester and they were to actually be testing and their levels were to fall more quickly, it could actually indicate not their inability to be able to be in a state of ketosis, but rather it could indicate that they are using ketones more efficiently because they're disappearing from the bloodstream more rapidly, therefore being used as energy more readily.

Yeah, exactly.

Well, I suppose that's probably a good business model for you guys because it means that the more you use the stuff, the faster your body's going to be able to burn through it, huh?

Yeah, yeah. And look, it's, it, it's a really interesting context, right, because ancient humans spent had had more elevated ketone levels, right? Like there was no Reese's peanut butter cups on the savannah. People were moving around 5, 6, 7 miles and clearing excess carbohydrates that they had. So I, you know, open question. Were people doing full blown ketogenic diet, zero carbs? You know, I don't think so either because, you know, there were berries and fruits and grains and people had some access to carbohydrates, but it was not the same nutritional context that you see today. So it's safe to say that ancient humans had more elevated ketone levels than modern humans. And their bodies were better at making ketones endogenously as well as better at what we're just discussing, you know, processing those ketones and putting them to use. And our whole mission is to, you know, do all of those things, right, like eat lower carb, exercise more. And also the way I think about it, the way we think about it at HVMN is having access to a drinkable ketone is just another tool in the toolkit for metabolic health, another way to elevate your ketone levels, get in touch with that, that feel, that really subjectively good feeling and get more aligned with how ancient humans used to, how their metabolic profile used to be.

Yeah, yeah, okay, that makes sense. And of course, back to the state of natural ketosis. These ketone bodies, they're three little water soluble compounds that are produced by your liver. Liver, typically in response to reduced fuel availability or reduced glucose availability. Really? So you have these ketone bodies that would be. Now I got to think back to my biochemistry days. We got beta hydroxybutyrate, acetoacetate and. What's the last one?

Acetone.

Okay, I get a C on the test. Acetone. So basically these are the ones your body would produce and burn for fuel in a state of ketosis at a relatively efficient pace. Again, back to ochem and biochem, essentially the delta in terms of the energy trade off for producing energy from ketones is relatively low, which is why the body would shift to preferring those as a state of or as a form of fuel, in a state of starvation, or in a state of caloric deficiency, or in a state of carbohydrate deprivation or something like that, that. Now when we look at the ability to be able to get the same cognitive benefits or get the same longevity benefits or anti inflammatory benefits that these ketones produce, which is one of the reasons why fasting can be so good for you. When you're looking at these three forms of ketones, acetone and acetoacetate and beta hydroxybutyrate. This ketone IQ stuff, what is it? Is it like a blend of all of those? Is it some different form of ketone that the body also recognizes? Or when we look at the this from a biochemical standpoint, what exactly is it?

All these ketones are interrelated, they're always swapping, there's flux between these as your body is doing metabolism on an ongoing basis. Our ketone IQ is in the BHB family. So Dom de Agostino, you mentioned at the top, he has done a lot of research around acac. We have, our product is in the BHB family. It's very specifically a butane dial. So BDO butane dial that quickly first pass converts into BHB in your liver. So that's why you see the instantaneous rise in blood BHB level. And that's what's generally tracked. Like when people are doing, you know, blood prick, if you have your Abbott precision extra or you know, keto mojo, these kinds of blood pricks, or you're doing the breath test or the urine test, the main one that you're measuring is on the blood test is the.

BHB is the beta hydroxybutyrate versus like a urine test, in which case you'd be measuring acetone or acetoacetate metabolites. If you're getting a blood test, usually it's telling you your BHB versus a breath or a urine.

Yeah, okay, the urine measures that one while the blood measures the bhb. And that's why I prefer the blood because the blood is just the direct. What are you trying to measure is your blood ketone level. So urine and breath are kind of an indirect measure. You're trying to measure your blood's BHB content. And so the most direct way to do that is just do a blood drop that measures your bhb.

Right. And BHB particularly. And this is based on the research of Dominique d' Agostino and many others. Even compared to a very high fat ketogenic diet, oral BHB seems to be really rapidly absorbed and metabolized and increased blood ketones at that millimolar level to a very appreciable extent and appears to be one of the more ketogenic ways to get into ketosis, if that's not too redundant a way to phrase things. You know, compared to say like MCT oil or a high fat diet or something like that, some form of BHB appears to be superior. Now what you're saying is that you guys are using a form of bhb, but it's in a specific configuration that is different than others that may have been used in the past.

Yeah, yeah, so we could talk about that a little bit here. So BHB free acid, it's, it's, it's literally acidic. If you have a cup I got drink straight BHB free acid. It is acidic. It's like a cup of lemon juice or citric acid is very acidic. If you want to drink straight bhb, you're going to have GI issues, you're going to be, you can drink a little bit of it, but then you just cannot drink enough to meaningfully elevate your blood ketone levels. So there's this cousin, you know the straight good stuff that's called, called BDO butane dial that your body, it's one step away from a ketone. It's a very trivial step that in your liver just first pass gets converted into your bloodstream into that BHB and that BDO is much more palatable. So on our ketone version one what we did was we, we esterized the two, we esterized the BHB free acid with this butane dial. So it was just one to one and you had a double bond between these, sorry single bond monoester ketone monoester that bonded this BHB free acid with the butane dial and then your body would cleave that bond, the BHP would enter your bloodstream, the BDL would go to your liver and enter your bloodstream. What we did for the second generation that we just launched here was we just simplified it that esterization. One way I think about this is everything's obvious in hindsight, but we kind of over Ferrari engined it. Like we built the eight track player. Like the most novel cool way of like hey, let's bind these two things together, let's make this super thing and like it was expensive. I don't I don't know if you remember. I'm sure a lot of your listeners remember. Like our version one cost $30 a shot. It was not cheap.

Well, yeah, I mean, like, you know, I've gone to, you know, Sigma Aldrich website, for example, to purchase laboratory chemicals and you know, any, any racemic configuration of 13 butane diol is not inexpensive, you know, because I've thought about hacking this before and just kind of of doing it myself. And honestly, you and some of the other folks in the ketone ester community have figured out how to make it taste better than you get off the shelf from Sigma Aldrich. So I'd rather go to the people who are actually adjusting the flavor profile a little bit better. But ultimately the R13 butanediol is the actual chemical that you guys are using in this new ketone iq. And that one appears to pretty remarkably be able to convert into beta hydroxybutyrate for elevated ketone levels, even compared to some of its precursors.

It was always half of what was in our version one, right, because it was half of that ester bond. And for our version two, it just isolated that. And we've pushed a lot on the manufacturing innovation. So there's a few different ways to make this. There's a biosynthesis route where you take genetically modified bacteria, you feed it sugar, it poops out ketones, it poops out that R13 butane dial, and then you clean up the bacteria and other waste products and you end up with your target molecule. That's one way to do it. Totally plant based, renewable. There's another way to do it. That's an enzyme process where you put, without going too technical on it, you put A and B in a vat with an enzyme, you stir it up and that turns into your target molecule, your R13 butane dial. You clean up all of the A and B and side reaction products and you're left with your target molecule. Oftentimes not all the time, but sometimes this, this enzyme process uses petrochemical petroleum as an input. You can also use other things like sugar. So there's a lot of innovation on the manufacturing stack between the biosynthesis, which is more new and renewable, and then the enzyme process. So that's a lot of.

Where we, is it proprietary? Are you able to share in terms of what manufacturing process you guys are using?

We're straddling both. We're so early right now that we are part of the reason that we've been able to move Quickly and bring down the price is we are just looking under every stone. I would say we're preferential towards the biosynthesis product. Like if you look very candidly, if you pick up our product right now, what is inside of it is maybe a biosynthesis. We like it for a few different reasons. I think the renewable point is very interesting. It can be entirely plant based, carbon neutral like that. That's very nice. The enzyme process also interesting. Maybe there's, you know, cost implications, other things going, going on at play there. Right now our stance is let's turn over every stone on how best to deliver ketones and explore all the routes. Right now the biosynthesis kind of renewable route is, is our favorite. I honestly I do think that that is third. I don't want to overly commit because look, we're looking under every stone. Things can change every six months. But yeah, it's, it's a super interesting area for us that we're looking at.

Well, it seems to be remarkably cost effective. Like I mentioned, if I were to go Sigma aldrich and get 1,3 butanediol, I'd probably pay for 10 grams, around 70 to 80 bucks. Last I checked, it looks based on your label because I've got a few bottles of your ketone IQ that you guys sent me. And by the way, it works fantastically as advertised. I mean you take a shot and you just don't think about eating for quite some time. Although I, I usually dabble more in the 2 to 3 servings type of range just because I, I like to do a little bit more of everything. But regardless, 10 grams is a serving. And so you've got, you know, you've got $120 for a whole bottle of this stuff which would come out to like 12 bucks for 10 grams.

Sorry to interrupt. No, it's 40 bucks. It's a hundred dollars. 120 for three bottles. 40. 40 bucks a bottle.

Okay.

And a bottle has 10 servings in it.

Oh geez.

So we're talking four dollars a serving.

So yeah, basically I'm paying four dollars for a dial that I'd normally pay 70 to 80 dollars for from a lab chemical website. It seems like you guys have figured out some way to actually very cost effectively get this stuff bottled up and chipped out. So correct me if I'm wrong, but this is one of the least expensive ketone esters I've ever seen.

Yes. Okay, so our key metric is elevation of blood ketones per dollar. That is what we care the most about that is our promise as a brand is to get you as much area under the curve of ketones for as cheap as possible without GI or any side effects that you would have from ketone salts, et cetera. So we're not trying to make the most novel ketone, the most fancy, the most what, like none of that. What we care about. My background is I studied product design and computer science and got into biohacking and from there got into nutrition and started looking a lot at ketones. I come at it in a sense from a layman's perspective. Just like I want the best product value, I want the thing that can deliver the best ketones, the best area under the curve per unit dollar. I'm not trying to win a Nobel prize or get published everywhere in the white papers. I want to deliver the best product experience.

It seems to deliver as promised in terms of the affordability and the roi, like cost, match up to other existing ketone options. In terms of the length of time. Do you have or have you guys experimented much with average length of time? Because for me it seems to be somewhere in like the, well really the four to six hour range for peak. Even though I still typically about eight hours down from taking it, still seem to experience some of the. It's it for, for me really Michael, it's. It's mostly like the I'm not hungry hungry type of effect, which can be dangerous because sometimes if I'm not hungry and I go to do something extremely glycolytic in the gym, like weight training, that can come back to bite you. Let's face it, even though many studies show that mass gains, that glycolytic power strength type of activities are certainly doable on ketones, they tend to be somewhat inferior if we paint with a very broad brush. So not being hungry at all can come back to bite you, pun intended. I suppose in this case if you head off to the gym and you haven't eaten in eight hours. But regardless, in terms of the amount of time that something like this might last, how are you guys kind of using it? Because obviously it's kind of new, but like, let's say internally, hvmn is it kind of like a couple of shots a day, three shots a day, a whole bolus in the morning? Like what have you guys found to be best in terms of the effects and the longevity?

The best way to do it for performance is the benchmark is 500 milligrams per kilogram of body weight. So that ends up being, I Mean, you can do the math on it. Like your kilogram body weight, it ends up being, you know, somewhere it depends how much you weigh. Like 30 to 50 grams. That's what you would have if you are gonna really dial in for performance. That's what we, that's what we target towards with our U.S. sOCOM Special Operations Command. That's why I would say if you're gonna go run a marathon, right?

So, so for a guy like me, it technically be like four servings. If I, if a serving contains 10 grams, I, I could because I'm around 80 kilograms. So I knocked back four of those at 500 mgs per kilogram. Then that, that'd give me pretty close to about 40 grams of be. Like that would be like gold standard if I really wanted to crush the day.

Yeah, yeah. And then, and then we made the dose size smaller. We made the dose size 10 grams so that you can just have one serving. If you're, look, if you're not going to go run an ironman, if you're not going to go beast mode on it, you just want to sip it at work. Like that's a big thing we're seeing is people will have what, 10 grams of ketones and mix it in with their diet soda and sip on that at work or they'll have it as a shooter in the afternoon. Because, you know, I think more and more I'm hearing a lot of people like are hiring, setting a hard rule like I don't drink caffeine. Afternoon distress, my sleep patterns too much. My aura ring, you know, barks at me. I don't touch caffeine after noon, 2, 3pm rolls around. You know, I also know sugar is bad for me. I don't want to be drinking a soda or spiking my blood glucose. My blood insulin in walks ketones as this way to elevate your energy level and not spike your glucose. Not be, not contain caffeine. But do you need to have the Navy SEAL super, super dose for that kind of context? No, that's where like the, there's, there's some modulation to. You can have, you know, a smaller amount and there's, you can kind of adjust the dimmer switch if you will on how much that you want for the context that you're going for.

Yeah, yeah.

So we're seeing a lot of people that are, that are having you know, two, three shots throughout the day and just like drinking it like just as it kind of keep, keep zippy, stay in flow state throughout the day. Stay in that, that flow state. Appetite suppression, which is actually something we should, we could talk about too. Like it's that perception that you're having of, hey, my appetite is suppressed. I mean that's real. Like we've seen ketones mediate ghrelin. So like the hunger hormone, like when you compare ketones to the same amount of calories, so you take 80 calories of ketones versus 80 calories of glucose, the ketone will make you objectively less hungry. It's important clarification. There's like ketone is not this like magic thing that has no calories in it. There are calories in ketones. It's a source of energy. But it is a more satiating form of energy. Energy that lets you stay in that flow state, crank through work and not need to interrupt yourself with a meal.

Right, exactly. Because if you look at like a serving of your ketone esters, Obviously you got 70 calories is right there on the label for 10 grams of R3 butane dial, you know, which, you know, I, I would say you're getting the mental ghrelin suppressing equivalent of perhaps a 700 calorie meal. So it's definitely a speed bump in terms of calories. But if you look at, you know, the suppression of ghrelin and most of the studies I've seen, you know, you're looking at anywhere from like one and a half to two kilocalories per kilogram. And so again, like a guy like me, let's say I'm at 80kg and would need 160 calories for the significant ghrelin suppressing effect seen in literature. You know, I'd still be at around like 1 1/2 to 3 servings around in there. So maybe a little bit more than what's on the label to get the, the potent appetite suppressing effect that literally is like go all day long without eating. But it's still pretty darn impressive in terms of the appetite suppression. And I think there's some other things going on in terms of ketone bodies when it comes to kind of like not only not eating, but probably more importantly, and I don't know if you agree with me here, Michael, not eating, but not being in a catabolic state when not eating. For people who are concerned about protein synthesis or, or MTOR activation, from everything I've seen, ketones may actually increase MTOR activation and basically cause a little bit of an upregulated muscle protein synthesis and basically serve as an anti catabolic agent. On the skeletal muscle specific level, even if you weren't consuming a lot of fuels along with them kind of in the similar way, I guess I could draw a parallel between like say if you can't exercise and you do hyperthermia and amplify heat shock proteins via something like a sauna practice, you appear to be able toto maintain or hold onto muscle. It kind of seems similar to ketones. It's like if you can't have protein and can't eat a lot of calories or want to fast and not lose a lot of muscle, then ketones seem to actually allow for a little bit of that effect.

Yeah, that's exactly right. And I appreciate the nuance there on. When we're talking about fasting and like, are ketones good to have on a fast? It, it really depends on what your goals are from fasting. Right? Like have your goals from fasting to stay away from any glucose or insulin spikes and improve your metabolic health and spend time with elevated ketones, in which case, yeah, like sipping a ketone and being able to preserve muscle protein is, is a great idea. At the same time it's, you know, ketone. We said before, like ketones are caloric. If your goal of a fast is to be in a calorie deficit, then it's more of a question of like, oh, is ketones going to help me? Maybe like if ketones is a kind of crutch that prevents you from having more calories or you know, worser quality of calories and maybe ketones are, are still helpful there. But I think there's a, there's a debate to be had on like, are ketones fasting friendly or not? If you're strict, like strict, you know, strict and constitutionalist about it. It's like fasting means no calories are calories.

I mean, if you're like a Dr. Sachin Panda kind of guy, fasting means no coffee or like anything that that enters, enters thy lips is breaking the fast. So yeah, it kind of depends. But I, I agree they as far as kind of like ranking on the totem pole of the things that you could consume that would be most friendly to the, the purposes that people would be fasting in the first place, it seems like a pretty good idea. You know, there the impact on sleep because a lot of people like, well, you guys are describing it as almost like a nootropic is almost something like caffeine. What's it going to do to my sleep if I have elevated levels of ketone bodies before I go to bed and I think this is a really interesting one to think about for a few reasons. A, you know, you look at folks like, I think Dr. Rhonda Patrick, the last time she was interviewed on the Joe Rogan podcast, talked about using ketones as almost like an anxiolytic to decrease anxiety prior to her, like being on a podcast or something like that. And I know that there have been some studies that have looked into the effects of ketones on increasing hrv, which may back that up. Like they may actually have an impact on vagal nerve tone. Maybe that's because they taste like ass. I don't know. Sometimes bitter things help to tone the vagus nerve. Or maybe it's an actual ketone effect. And I know that a lot of like rodent models have shown cognition, sparing and anxiolytic properties. But I think what's most interesting, and I know this is a little bit controversial, but if you look at, for example, you know, the old gamma hydroxybutyrate ghb, AKA the date rape drug, that seemed to be one of the best ways to induce like knock me out right now sleep, that didn't deleteriously impact sleep architecture until the feds made it illegal for obvious reasons. That was basically one four butane dial or something very, very close to one, four butane dial. So when we're looking at 1, 3 butane D, it kind of. Well, there's a couple of things to think about here. A, pretty potent GABAergic effect which would dictate that, at least for me, it seems to impact sleep favorably. And B, the fact that you don't want to mix 14 butane dial GHB with alcohol because it can tend to have an extremely sedating effect. I've actually, when using any form of ketone, found that it has a comparable effect to having a cocktail at night. And also that if I have it with alcohol, I get excessively sleepy. Which you could use to work for or against you, depending on however you want to use it. But what's been your own experience with ketone esters and sleep?

That's a great question. It's definitely area of more investigation. I think you tapped on a lot of the interesting areas around elevated hrv. One really interesting study that came out was around recovery. There's a researcher named Peter Hespel who did a three week study, two workouts per day. This is designed to emulate, you know, elevated training blocks. So two workouts per day for three weeks. And there are two wings, one included ketones and kept calories the same compared to the placebo. And at the end of those three weeks they saw, well, okay, the important thing is people were having ketones three times a day, day, including half an hour before bedtime. So half an hour before sleep they're taking ketone. At the end of these three weeks, they were seeing. The participants in the ketone wing were experiencing a 15% increase in training volume and 5% increase in performance on the last day of the trial time trial. And so there is really compelling evidence around ketones for recovery. And again, people are having a half an hour before sleep. And so this is where the Tour de France we've sold to 60% of the teams on the Tour de France. This recovery area is massive and possibly even more interesting, more impactful than the performance aspect.

Do you think that's because it's promoting MTOR signaling?

Yes, because it's accelerating that muscle glycogen uptake, accelerating protein synthesis. And there's a lot more to uncover around brain network stabilization. Like all the, all of the good things that happen when you sleep. Are ketones also helping to amplify those recovery that takes place when you're sleeping?

Yeah. That's fascinating. Huh. I wasn't aware of that. In terms of the magnitude of recovery implications, I think there's also when it comes to protein synthesis, I believe it's leucine mediated, but I suspect that's probably why, and I don't want this to sound like a shameless plug, but it may I really notice, notice quite an amplified effect when I combine ketone esters with essential amino acids which do have some leucine in them. And that might be due to the leucine mediated protein synthesis effect of the exogenous ketones, amplifying the effect of the essential amino acids even more. It could also be due to the fact that the essential amino acids might also be modulating the GABAergic effect just by providing more amino acids as neurotransmitter precursors for ketone bodies to interact with the nervous system. But that seems to be a pretty favorable stack for the recovery is ketone esters combined with essential amino acids. Have you mixed those two at all?

Yeah, I think that's a great point that when you are going for recovery, you have ketones with your gold standard recovery drink and it will help your body to uptake that stuff better. That's, I think a really important point. It's not just like ketones alone. If you don't have the amino Acids present like you're, you know, you have these, all these micro tears and, and abrasions that happen when you're exercising hard. Your body needs to recover from that. Like ketones are. You can think of them as a, like a multiplying force on the gold standard nutrition for that recovery context.

Yeah, yeah.

And it's super interesting by the way. Like right, we're talking about fasting, we're talking about recovery. It's like there's all these different ways that ketones can be applied and I think just zooming all the way out the root way I really think about ketones and why I'm so excited about it is that think about it as a nutritional primitive like a Tour de France cyclist is going to work use it differently from someone who's doing intermittent fasting is going to use it different from Alzheimer's patient. Everyone is doing metabolism all the time. You know, all 7 billion of us, we're doing metabolism all the time. And we all have these different objective functions that we're trying to optimize for and so it's not like this one way to go and use ketones for. For. It's a tool in the toolkit for metabolic health and performance that anyone can use for their given objective function. And there's a lot of nuance in what exactly you're applying it for. And you know folks way smarter than me, right like Senior PIs at UCSD who have been looking at cancer research their entire career and are looking at ketogenic diet and exogenous ketones for to see the application there like there. There's a lot of knowledge being created there. So really my mission, our mission is to make it goes back to that like ketones per dollar. Like make ketones as available and accessible as possible so that all the good researchers can create new science, can create new knowledge around with macronutrients.

Yeah, I'll, I'll leave, I'll leave the. Are you even metabolizing bro T shirt design up to you. But, but you know the essential amino acids would of course be one thing thing. And we talked about carbohydrates and gave a head nod to the idea that for performance implications having elevated blood glucose levels and elevated ketone bodies is actually pretty remarkable when it comes to performance. I mentioned I've done that. I think the gal who set the world record in the hour in cycling, Vittoria Busey, used a ketone ester carb combination for that record setting performance and anecdotal totally. I've Talked to many others who, particularly for performance, don't do this all sitting around your desk at work because you're basically mimicking a very, very mild form of ketoacidosis. So you don't want to do this when sedentary. But if you're out performing and you combine carbohydrates, whether it's like a Vitargo or a glycofuse type of highly digestive or digestible starch, with a ketone ester, whether it's essential aminos plus carbohydrates plus electrolytes plus ketones, which is generally what I tell all my ironman triathletes to do when they're training, is it's basically a serving of ketones per hour, about 100 grams of carbs per hour, about 10 grams of essential amino acids per hour, and then a couple scoops of some type of electrolytes like thorn catalytes or element or protect or something like that in their water bottle. You just go for hours and hours on that blend of salts, amino acids, ketones and trace amounts of carbs. But then there's some other things too. Caffeine seems to amplify the effects of ketones quite a bit. Sodium bicarb, which is basically just baking soda, which we know is kind of like one of the cheapest, most studied, most effective ways to help reduce lactic acidosis and performance. Burnout and decreased rating of perceived exertion in the gym. Sodium bicarb levels seem to be slightly decreased after ketone ester ingestion. And so adding a little bit of sodium bicarb in with your ketones could be another way to, to stack. Right? So you've got caffeine as one option to consume with them or in my opinion pretty much any other nootropic like caffeine or smart drugs or Kratom or anything seems to blend really, really well with ketones. Sodium bicarb would be another. And then I actually had a dinner with a maps researcher a couple of years ago and we were sitting at a dinner down in San Francisco and I actually remember this. It was at China Live, a restaurant down on there. And he started telling me about the amplification in plant medicine journeys and experiences, particularly regarding like visualization and what people could see in their heads and the so called like you know, third eye, you know, the ability to tap into the third eye when in a state of ketosis, particularly very elevated ketosis by using ketone esters prior to plant medicine experiences. So, and I can say Just like anecdotally, you know, I might do an experience like that one to two times a year. And these days, you know, of course I'm always faceted on some sort of dieta going in, but then I typically, even though one is encouraged not to eat anything at all prior to using plant medicines, I will do a shot of ketones now before I drop in, so to speak. And I think that it definitely amplifies the experience, at least subjectively, so I'll shut up now. But how about you, dude? Have you found anything aside from what I've talked about to stack well with ketones?

There's a couple of things in there to really highlights that the, the bicarb, the sodium bicarbonate as a buffering mechanism is super interesting and actually major study done around that with, with a Belgian group around cyclists. And I know it's something that when you last time you chatted with my co founder Jeff and you kind of hypothesized around, this is uncanny. This study not done by us and done by third party Belgian researcher, they found literally exactly this, that if you dose bicarb slowly, again emphasis on slowly, don't want to have a giant bolus of bicarb all at once, you'll have, you'll have a bad, a bad time, GI issues. But if you dose it slowly, you know, three times in their study, they did three times over an hour and 40 minutes or a total of 150 milligrams. Up until the performance period, the blood was less acidic. So they're taking bicycle carb and ketones. And because there was this whole issue, right, we're like, okay, ketones work, so let me have more ketones. Ah, but there's, there's a limit to it. If you have too much ketones and your blood goes too acidic, you actually start to diminish and blunt the effects, the goods, the good effects of ketones. So there's a special synergy with if you take bicarb buffer that then you get the benefits of the ketones, but you're not going overly acidic. And that's actually one thing too that, that led to our evolution from V1 of our product to V2 of our product, which is that V1 of our product launched in 2017, super expensive. It like it spiked your ketones like too much too quick. And looked at the science, we're like, hey look like there's kind of this magic sweet spot like 2 to 3 millimole. And like once you start going too far north of that Too quickly, it starts to backfire and be counterproductive. So with the, with our V2 here, our ketone IQ, it's a slower, gentler ramp. So it gets you into that ideal zone and keeps you there for, for longer without overly spiking your blood ketone level, making you go overly acidic. I personally still have small dose of bicarb just to completely smooth that out so that you're not going acidic at all.

And when you say small dose, just so people know, because I know some people don't quite understand the gram levels we're talking, like if you were to throw back a shot of this ketone IQ and take about half a teaspoon or so of sodium bicarb, that, that's a. At least for me personally, that that's right around the range that we're talking is. Is that ballpark in your opinion, Michael?

Yeah, yeah. Yes.

Yeah. So you don't, you don't need much.

Yeah. And then the ayahuasca stuff's super interesting too. Like that people have known for. It's always been part of the ceremony that you do this like extended fast and purge. And it's always been couched in like spiritual language. Like this is the voyage. Like you march out to the hut in the middle of the rainforest and don't eat for a while while. Part of what is going on there is when you're doing this extended fast and purge is, you know, your body is going to a calorie deficit and producing ketones. So it totally matches up that you would want to have a. You could compound onto that effect by having an exogenous ketone. Like ketones do interesting things in your brain. Like they are able to activate your brain in a way beyond what just glucose alone can do. And that's where, you know, we have a lot of interesting research going on with Alzheimer's and tbi. Some of the findings there and some of the, some of the new hypotheses there can also extend into healthy adults. It's. It's. Sometimes you can see the more pronounced effect when someone has tbi. Right. Like it's. It. You can see sometimes in the science you can see more of impact of a given of the ketone. When you're applying it to people who are at a deficit due to a TBI or, or Alzheimer's. You're able to like recover cognitive function and then the same effect can carry over to a healthy, the adult as well. You basically, instead of going from like a, you know, below baseline, like up towards Baseline in a. In a patient, you're seeing for. In a healthy person, you're seeing like you're going basically like above baseline.

Yeah.

Your brain is able to have more metabolite available. It's able to create more ATP with less oxygen, and it can dive into that a little bit on, like, the Alzheimer's, tbi. So some really exciting stuff there too, if you want to go there.

Yeah. And in particular, you know, and this is based off of research that I know Dom's been doing since like 2015. Seen when you combine the elevated ketone bodies with increased pressure and availability of oxygen, there appears to be a cytotoxic effect on cancer, meaning that cancer growth seems to be slowed. And I know that similar studies have been done on Alzheimer's and dementia. And I want to hear what you guys have found regarding Alzheimer's and dementia here briefly. But then regarding what you were talking about with plant medicines, I would also be curious, and it really wouldn't surprise me if this were the case, if ketone bodies may lend themselves to the formation of a tryptamine, like 5 Meo DMT or something like that via interaction with the pineal gland and therefore allow for greater DMT production. I haven't seen any studies in that regard, but it'd be very interesting. What were you saying about Alzheimer's?

It's super interesting what you just said there. We know Alzheimer's is an issue of metabolic deficiency in the brain, like ATP deficiency in the brain. It's. It has to do with insulin resistance that accelerates its progression of cognitive impairment as you age. We show that neuroimaging has shown that this is linked to brain glucose hypometabolism. Like not. Not enough metabolism is going on in your brain because it's. The glucose ain't working. And also studies have shown a correlation between diabetes and Alzheimer's. So there's like this link between Alzheimer's and insulin sensitivity that's pretty hard to ignore at this point. And there's also a dot to connect over to other broad neurological and neurodegenerative disorders. So tbi, traumatic brain injury, concussion, when you have a blunt trauma to your head, that causes some damage upon impact, and it also causes ongoing damage because you have this swelling, this inflammation that causes hypometabolism. You are not able to get enough glucose in there. You're not able to produce enough ATP, and that causes further neurological damage. So we actually just submitted a $1.25 million research proposal with the Naval Health Research Center. To look at ketones for people with chronic tbi. There's two hypotheses there that are related but a little bit different. One is around anti inflammation. Ketones can reduce oxidative stress. If there's metabolic dysfunction and the neurons cannot clear the oxidative stress, they cannot clear the rods, the reactive oxygen species, then that causes oxidative damage, causes inflammation. If ketones can reduce that, that's super interesting. And then the second is around just glucose metabolism. If glucose metabolism just is not working, then what about going around that, you know, the glucose goes through the PDH pyruvate dehydrogenous as a gating factor. What if you can go around PDH glucose pathway and you're not pdh limited ketones are not PDH limited ketones do not require insulin. It's a fresh metabolite that your brain can potentially use. And ketones are more efficient, perfect per mole of oxygen. So it's not this like magic cure all necessarily. Like this is all kind of cutting edge of research. But there's some interesting hypotheses that ketones can recover this deficit. Right? For Alzheimer's, for tbi. And then yeah, it stands to reason for a healthy human adult that you might be able to get a surplus of cognitive ability if you're taking a ketone.

Right. Interestingly, both in terms of metabolites that can cross the blood brain barrier and serve as stable sources of fuel, particularly for an inflamed brain, as would be the state in something like Alzheimer's or dementia ketone bodies. And interestingly, lactate, if you actually have elevated levels of lactate, that also is a pretty stable fuel source for, for neural tissue. And therefore again, when we step back and look at stacking either something like, let's say blood flow restriction training to increase blood lactate levels pretty appreciably compared to normal exercise in a state of nutritional ketosis, as an exercise intervention for people with Alzheimer's or dementia, or as a cognitive hack for the average biohacker listening in who just wants to crush the day and maybe, you know, take some ketones and do a bout of blood flow restriction training, flood the brain with lactic acid, maybe toss some brain derived neurotrophic factor stimulating substances like lion's mane or psilocybin on top of that, and you're looking at a pretty good day, most likely from a cognitive standpoint. So the sky's the limit when it comes to the way that this stuff can be kind of expertly combined and stacked. And of Course, I always tell people who are listening in definitely as you are listening, if you have your own, own ways that you like to use this stuff and you want to contribute them to the shownotes, please do go to the shownotes@bengreenfieldfitness.com ketonepodcast and leave your comments there. Michael, anything else you want to add in about this new form of ketone? This 1,3 butane dial in the form of the new ketone IQ that you guys are now producing?

One thing I'll say I think is really exciting, it's kind of late breaking news from last week at ces, the Consumer Electronics show is. I don't know if you.

Which I really wanted to go to, but I had to be vaccinated.

Yeah, I don't know how much you missed, like in person. I think a lot of the show is wound down. But one really exciting update to come out of that was Abbott announced this project lingo where I think a lot of people at this point are familiar with continuous glucose monitor. Like the sticker that you wear on your arm. Yeah. That goes, you know, measured blood glucose level. Abbott lingo is they're basically releasing a continuous ketone monitor. And a continuous. And a continuous. Yeah, and a continuous lactate monitor as well. So it makes total sense. Right. It's like glucose, obviously, super interesting to track, but it's only part of the picture. And being able to have an ongoing read of your ketone and your lactate level, super interesting.

Well, Abbott produces the Freestyle Libreo.

They correct? Yeah, they use Freestyle Libre. That's also the hardware that powers levels, which, you know, friends with the folks at levels like they've made, I think like a sexy UI UX wrapper around the Abbott Freestyle Libre. But yeah, Abbott's mass. I mean, Abbott's the size. They're a $240 billion public company the size of Toyota. Like, they make a lot of medical hardware. This is big news.

Yeah, that is big news. And whoever's working at Abbott listening in right now, please send me up that sensor once it's ready to. Although what would be really cool is if they're able to combine that with tracking other key signals in the body. Obviously they can do glucose already, but if they could also do, for example, another molecule I just mentioned, lactate and have a sensor be able to, from a bio wearable standpoint, do glucose, do ketones and do lactate. I don't know anybody who'd want to have like three sensors slapped on their body all at once. That'd be pretty sick.

They are. So yes, they're yes to all of that. They're doing glucose, glucose ketones, lactate, and they're actually doing alcohol so you can see your blood alcohol levels so you don't get pulled over. Super interesting. And funny enough that I didn't, I didn't, I saw the news and I started, you know, tweeting about it and posting about it. One of my old buddies from college is actually the product manager over at Abbott and we, you know, we sent over our ketone version one over there. So they're definitely tinkering around with our products there because, you know, you think about you're inventing a ketone sensor. How are you going to elevate your ketone levels to make sure that your sensor is working well? Okay, you can fast for four days, you can do, you know, eat no carbs for a week or you can just immediately directly get into ketones by drinking HMN ketone or you know, there's other ones out there. But you know, again, our claim is that we're the best elevating ketones per dollar. So I would say, I guess on a wrap up note here, it's, there's a whole ecosystem going on right now. There's innovations in hardware, innovations in nutrition, updated understanding on the market of what, what people are putting into their body, what they're getting out of it. It's all connected and it's, yeah, it's a really exciting time. I think human body is a super exciting platform for innovation. Your body is the most advanced piece of hardware that you'll ever own. And we're just finally, I feel like we're in the first inning of really even understanding what's going on inside your body. And once you understand what's going on, okay, what are you going to go do about it? And obviously, Ben, you've been trailblazing in this stuff for a decade plus and I think that the average person is going to be catching up in the forthcoming decade.

Interesting. Well, one thing that I'd leave people with just from a practical standpoint is my recommendation at this point would be try skipping breakfast a few times and instead do anywhere from depending on your size. And based on what you learned in this episode, one to three shots.

Shots.

And if you would like to combine it with coffee, a little bit of baking soda or your nootropic of choice. And I should mention that both fish oil and CBD seem to be two other compounds that in CBD in like a 10 to 20 milligram dosage. Fish oil and like a 4 to 6 gram ish type of dosage seem to pair pretty well from a cognitive pick me up standpoint with the ketones. So consider that. Consider trying a workout with blood flow restriction training, training and ketones, and preferably throw in a little bit of essential amino acids and then do that early in the day if you can. So you're basically flooding your body, your brain, particularly with ketones and lactate. So try that. I would recommend that if you are experimenting with this for sleep and recovery, try one to two servings before bed. Whether or not you combine those with a glass of wine or some type of alcohol to increase the GABAergic effect is up to you. But I would warn you, you can tend to get excessively sedated or sleepy by combining ketones with alcohol in many cases. So proceed at your own risk with that and don't do it around a tractor or any other heavy machinery. And then for those of you who are just productivity hackers, even consider perhaps getting a bottle of this stuff. Skipping lunch on a few days if you tend to need an extra hour during the day to catch up on some work, do a couple of shots of this instead of lunch and just come back and I dare you to tell me that you're thinking it for food, about food at all until dinner. It's pretty amazing in that respect. So there's a few ways to, for those of you listening in to get your wheels churning about how you might use this stuff, it's called Ketone iq. I do know we have some special discounts for it. I don't remember what they are. I probably should have my ketones before this podcast. But anyways I'll put them all in the show notes if you go to BenGreenfieldFitness.com KetonePodcast and I'll also link to all the other work I've done on ketones, podcasts, podcasts, articles, the HVMN website, et cetera, et cetera. Michael, did I miss anything?

No. Thanks. This is a lot of fun and thank you Ben. All the good work you do as a practitioner, student, teacher of the game. This is a lot of fun. Appreciate your time.

Cool. All right folks, I'm Ben Greenfield along with Michael Brandt of HVMN, signing out from BenGreenfieldFitness.com have an amazing week. In compliance with the FTC guidelines, please assume the following about links and posts on this site. Most of the links going to products are often affiliate links of which I receive a small commission from sales of certain items. But the price is the same for you, and sometimes I even get to share a unique and somewhat significant discount with you. In some cases, I might also be an investor in a company I mention. I'm the founder, for example, of Kion llc, the makers of Kion branded supplements and products, which I talk about quite a bit. Regardless of the relationship, if I post or talk about an affiliate link to a product, it is indeed something I personally use, support, and with full authenticity and transparency recommend. In good conscience, I personally vet each and every product that I talk about. My first priority is providing valuable information and resources to you that help you positively optimize your mind, body and spirit, and I'll only ever link to products or resources, affiliate or otherwise, that fit within this purpose. So there's your fancy legal disclaimer.