Which Ketone Supplement Works Best: Ketone Salts vs. Ketone Esters With Dr. Dominic D’Agostino.

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We put our propeller hats on. In today's episode with Dominique d', Agostino, we get into ketosis. And speaking of ketosis as a nutritional therapy, I'm headed down to Vancouver in March and you should join me March.

3Rd through the 5th.

I'm speaking at this thing called the NTA Conference. Do you think I should keep you hanging on the edge of your seat wondering what NTA stands for?

It's actually Nutritional Therapy Association. You guessed it. They do therapy, practitioner and consultant certifications.

Meaning they teach people how to be nutritionists. But it's not like run of the mill Gatorade Sports Science Institute, sponsored by.

Power Bar and Kellogg cereal type of nutrition. Instead, it's like a really ancestral approach.

That focuses on nutrient dense whole foods. So if you want to be a nutritionist, this is the cert to get. So not only can you go to that conference, you register@BenGreenfieldFitness.com.

And tell them I sent you or you heard about it on this podcast to get the white glove treatment. I don't know why I just said white like that.

White.

I believe that's how they pronounce it in Europe and they're much, much more sophisticated than us over there, so I'm just gonna stick to it. NutritionalTherapy.com is where you can go, though, to learn about their practitioner and consultant certifications. But registration closes February 6th, so get on it. Nutritionaltherapy.com check it out. This podcast is also brought to you by something I had a giant cup of this morning. And that is K I M E R A K O F F E E. In case you did not spell that along with me, it is kamaracoffee.com cameracoffee.com they put things into their coffee, things you won't find in any other coffee.

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In this episode of the Ben Greenfield.

Fitness show, we understood ketones as an energy metabolite. But it would make sense that these energy metabolites, even Krebs cycle intermediates, the energy metabolites, are powerful signaling molecules. Those are receptors, receptors and pathways in our body and our cells that sense that. And there's downstream signaling that are impacted as a result of that. When you take mct, you make D beta hydroxybutyrate, mostly. Some of it may interconvert to the ill if the rasmate is there, but in large part, you produce D beta hydroxyhydrate.

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Hey, folks, it's Ben Greenfield. And it was a few months ago that I recorded this pretty controversial interview about ketosis with a guy named Dr. Richard Veach. And in that interview, Dr. Veech claimed that the form of ketones that most people take nowadays when they're using a ketone supplement, they can actually be quite dangerous. And his solution during that podcast was something called ketone salts. And you may have heard of these, they're extremely expensive, but according to him, a far more natural and safe and healthy way to get your body very quickly into ketosis for anything from, you know, like managing medical conditions to Improving cognition to increasing endurance, et cetera. And I actually, after that interview, was sent a few bottles of these ketone salts. And I tried them. Well, I tried them at home, just taking a few at the kitchen table. And for those of you who do the whole ketosis thing, if you're a nerd sitting in your mom's basement with nothing better to do than to measure your blood ketone values, then what you'll learn next is pretty intriguing. My keton shot in about 15 minutes from under one to above five. And then I did this again during a race, and this time combined it with drinking about 75 grams of pure glucose along with these ketone salts before a tough mudder event. And the results were equally as astounding. I had an extremely fast race, eating nothing, proceeded, actually won that race, proceeded not to eat for another four hours or so. And again, every time I measured ketones, they were through the roof. But my big question, and yours too, might be whether or not these fancy, expensive ketone salts are actually far better or safer than what most supplements have in them, which is ketone esters. And are ketone esters, which is what most people use, are those actually going to result in any kind of long term health issues? Well, I decided to turn to the man himself, ketosis expert Dr. Dominique D', Agostino, to give us his opinion on this issue. And Dom's been a guest on the show before. You may have heard of him. If you look into things like ketosis for everything from managing neurological disorders to performance enhancement in extreme environments to holding your breath for longer periods of time. He's a professor in the Department of Molecular Pharmacology and Physiology at University of South Florida. And that means that wherever he is right now has got to be warmer than the three degrees out my front door. And I would imagine he's in quite balmier conditions than yours truly. But his research is supported by the Office of Naval Research, the Department of Defense. A ton of different private organizations and foundations turn to this dude to really learn what's going on when it comes to ketosis. And he's no stranger to this podcast. He was a previous guest in an episode called A Deep Dive into how Navy SEALs, extreme extreme athletes and Busy executives Can Enhance physical and mental performance with the secret weapon of ketone fuel. So I'll link to that episode along with everything else that Dom and I talk about today if you just go to BenGreenfieldFitness.com Dom that's BenGreenfieldFitness.com Do M. So, that being said, Dom, welcome to the show, man. Welcome back to the show.

Yeah, thanks for having me on, Ben. Appreciate it. You know, I get a lot of great feedback from that original episode. That was quite a while ago. A lot has happened since then. Thanks for having me on.

Yeah.

And I can clarify some of the things that you were talking about. Ketone esters versus ketone salts. So what's actually in the products that are on the market right now are ketone salts. And I could delve into exactly what they are from a, you know, biochemistry point of view versus ketone ester. Get into all that.

Okay, so what's currently on the market that's available for people to buy? In most cases, that's a ketone salt. Yeah. Did I misspeak?

Did I. I think you described, you know, taking a bottle. If it was liquid form, it may have been. If it was keto force, which is a liquid, that's a ketone salt formula. But there's also, you know, ketone.

No, what I. What I took was exactly what. What Dr. Veach had talked about and what they. What they sent up to me. You know, what I did, I did misspeak. It's the key. I think I. I presented things completely backwards just a couple seconds ago. It's the ketone esters that are the. Really hard to get your hands on. Super expensive. And those were the ones that I, you know, like the 3000 or the $30,000 bottle, depending on who you ask. Yes. The ketone esters are the ones that Dr. Veach sent to me. The ketone salts are the ones that you can find in most products out there. So just a clarification. I'm not a complete idiot, but I speak wrong.

I put it under the umbrella. Yeah, no, no issue there. Because I put it under the umbrella of ketone supplement, and it's easy to get the two mixed up, and you could get an equally expensive ketone salt if you wanted to. So the expense just comes down to how. What kind of ketone salt you want to make and what kind of ketone ester you want to make based on your starting materials.

But in most cases, when somebody goes out and they buy one of these newer ketone enhancing supplements, they're purchasing the ketone.

Salt, not the ketone ester in most cases.

Absolutely. Unless you're, you know, getting it as a research chemical, which we do. I mean, we also make them in house, and I also buy them from a variety of sources, and we test in our lab, like, about 20 different types of formulas, individual molecules and formulations of them. But yeah, if you're going to go out there, the commercial products out there that you're familiar with, the marketing, you know, is a ketone salts are in that. And that's essentially you take the beta hydroxybutyrate molecule. You could do this with acetoacetate too, and we use that for other purposes. But beta hydroxybutyrate combined with a monovalent or divalent cation, which a fancy term for an electrolyte, a mineral, and that could be sodium or potassium, that's your, you know, monovalent cation that'll bind very tightly, ionically bind to beta hydroxybutyrate. And it's water soluble. You consume it and your ketone levels spike up quick. Or calcium, magnesium. You could make a lithium salt, a beta hydroxybutyrate. I mean, if you look at your periodic table, you know, strontium, barium, you could, you could make a lot of different types of ketone salt molecules. But the ones that are being sold out there are typically sodium, potassium, calcium and magnesium.

Pretty much all of them are just like beta hydroxybutyrate bound to some kind of a salt.

Exactly. Yeah. We use a lithium salt to acetoacetate for some experiments because acetoacetate has some unique properties. So a salt does not have to be sodium. And I Beach was talking about excess sodium load. I mean, we could. I have formulations of ketone salts that have no sodium in it. So it's just a mineral load. Actually tested one with a magnesium and got some blood work. And my magnesium was sky high. Maybe not a bad thing. I mean, you don't want it too high, but it was an indication that a beta hydroxybutyrate magnesium salt is actually very bioavailable. And we know people that are ketogenic dieting tend to run kind of low on magnesium. You definitely don't want to be low if you're running marathons out there. So that was very informative to me as I test these things. And you can also have a salt of an amino acid. So the basic alkaline amino acids would be arginine, lysine and histidine. And some people told me they've created a creatine salt and are sending it to me, but I have yet to kind of test that experimentally.

But so in the case of like a creatine salt or an amino acid salt, are you saying that beta hydroxybutyrate could be bound to a creatine salt? Or an amino acid salt.

Theoretically, Absolutely. You could make an amino acid, you know, balanced mineral salt with beta hydroxybutyrate. That. So you'd be delivering the ketones and also some beneficial alkaline amino acids, like lysine in particular. It's something that I add into my amino acid formula and balance out the minerals to supplement your electrolytes. So you can definitely do that, and that's what we do in the lab.

Now, what Dr. Veach was describing when I had him on my show was that to get as much beta hydroxybutyrate delivered into the body as necessary to get your ketone levels really high or to get yourself into a state of ketosis, that the amount of salt you'd have to have that bound to would be really high. And as you just alluded to, the salt would not necessarily need to be sodium per se. You know, you mentioned that you did it with magnesium, and your magnesium levels went through the roof. Or you could do it with lithium or these amino acid salts or creatine salts. But painting with a broad brush, does this just mean that any salt that you bind this stuff to, you have to take copious amounts of, potentially dangerous amounts of.

Yeah, he may not be aware he was speaking pretty much strictly about sodium beta hydroxybutyrate. And you could get sodium levels up, you know, fairly high to get into that, you know, 2 to 3 to 4 millimolar range. That could be putting a stress on your body. Conceivably.

Like, how much salt are we talking? Because. Because I know like. Like I personally will. Will take, you know, if you add up all the sea salt and stuff that I'm taking during the day, on a typical day for me, I'm consuming like a lot of times, 3 to 6 grams. Ish worth of salt.

Yeah. Okay. Yeah. When I first started doing this stuff, like, just testing and buying the sodium beta hydroxybutyrate from, like, Sigma, for me to get into that 1 to 2 millimolar range, like, bumped up above where I was already at.

I was getting about that amount, up to 10 grams of salt per day and through multiple dosing during the day. So that's why I realized quickly that, you know, the sodium could get you there, but it's. You know, the sodium by itself tasted kind of horrible. But what all the work was, you know, to bring this to the market, you really had to balance out the mineral with potassium and other minerals and also formulate it with, ideally with a carrier. Because when you consume sodium beta hydroxybutyrate What I noticed, and I also noticed this with the mono esters of beta hydroxybutyrate, your levels shoot up really fast initially. And that, that's great if you want energy in like 10 minutes. If you get on your bike, you drink it and then go. And your energy is kind of there, but it also comes down and basically back to baseline within an hour with the salts and within hour and a half to two hours with the ketone ester.

Typically, kind of it depends on your dose and how much you take and whatnot. So we started formulating the ketone salts in a balanced preparation with sodium, potassium, calcium, magnesium, and formulating it with various MCT based powders, the C8 and C10 powders, and showing that if you give it, if you deliver the ketone salts with a ketogenic fat, it delays gastric absorption. And then the ketogenic fats also get broken down to ketones to beta hydroxybutyrate and then extends that pharmacokinetic profile. And then, you know, so you want to. So we kind of tested a bunch of different combinations and then figured out which ones were optimal based on the testing that was done. And then different companies have kind of got that and marketed that. And we're continuing to look at all the different forms of ketone salts and also ketone esters. We work with a variety of ketone esters in the lab and comparing them to figure out which one is most efficacious and which one's most potent.

I want to ask you about ketone esters here in just a moment, but when you're talking about these ketone salts that you've developed and kind of like mixed with MCTs, et cetera, and companies that then take what you've developed and use in their product. How does that work? I mean, because I know, for example, one that I'll use is Pruvit. And earlier you mentioned Patrick Arnold. I know he has one. I think it's called Ketocanna. And I've used that for example, for. Yeah, for free diving before, you know, to see if it would increase breath hold. And, you know, there's a few other companies now, a lot of them actually popping up that are producing ketones. But do folks approach you guys after you've kind of like figured this stuff out in your lab and like license that from you, or how does that actually work from like a commercial standpoint?

Yeah, good question. So I just, I just stay in the lab and do my thing in the lab. But we have Our university has a pretty good technology transfer office and patents and licensing office. And they will basically say, hey, what are you doing? Show us what you're doing kind of thing. And as we publish stuff too, they want it out there, but typically they want it before you get it published. Right. So to get it, to get a patent out for it. So as we are testing and screening things for the military work I was doing, some of the formulations that we were testing were kind of standing out as superior against other formulations where we could achieve a level of ketosis that was above and beyond what we could get with even the highest dose of things in isolation when we start formulating them together.

And also from not only pharmacokinetic profile wise, but also tolerability and palatability kind of factored in there. So our university will kind of, they just take all the raw data, all the data that they can get, and they continually ask, you know, and they look to see what other intellectual, you know, property is out there related to formulations and things like that. And if it's kind of something that's, that's a novel finding, a formulation that's a novel finding. Or you could get a composition of matter where you're creating different types of ketone salts, which, you know, we do in the lab too. We work with our organic chemistry department to do some things. And Patrick Arnold was really great initially as a, as a small company and an independent kind of chemist. That's kind of way out there and really forward thinking. Patrick was instrumental in helping me kind of develop my research program by developing, you know, ketone salts or ketone esters and later ketone salts. So essentially we do the research and then we have people in our technology transfer office that looks through all the research to see if anything is patentable, whether it be a new molecule, a formulation, or a novel application of ketones. Ten years ago, the only thing that the ketogenic diet was used for clinically was pediatric epilepsy. And now a big theme of our conference that we're holding, the Metabolic Therapeutics conference, is that the applications are exploding in all these different directions. And you have high end researchers at Ivy League institutions, you know, doing research on exogenous ketones to suppress inflammation, to activate epigenetic pathways that confer protection against oxidative stress and maybe can extend longevity. Like, you know, these are like Dr. Longo will be speaking about, you know, longevity and doctors Deep Dixit from Yale University will be speaking about the dramatic inflammasome suppressing effects of exogenous ketones at our meeting. So this is all new information that's just hitting now. We used to know that ketones viewed them only as a metabolite that supplied energy. And Dr. Veach did some fantastic, very spearheaded a lot of work to show that, that ketones are a superior metabolite in that their ability to generate ATP is greater. The delta G of ATP hydrolysis is greater for ketone molecules than for glucose for beta hydroxybutyrate. So, you know, we understood ketones as a energy metabolite, but it would make sense that these energy metabolites, even Krebs cycle intermediates, the energy metabolites, are powerful signaling molecules. So there's receptors and pathways in our body and ourselves that sense that. And there's downstream signaling that are impacted as a result of that. And these are metabolically independent, which means independent of their effects on metabolism. They have very unique signaling properties that are of high interest to the pharmaceutical companies because I know, because they've contacted me and they want to basically reverse kind of engineer molecules that work like ketones or specific pathologies. So it's an emerging field that really started emerging about four or five years ago. It's really new science.

Careful with those pharmaceutical companies, man. They have a lot of money. You might wind up with a garage full of Teslas if you're not careful.

I know one of the. I like to add that one of the pharmaceutical companies that makes the most common anti epilepsy drug out there is called Keppra, and that's made by UCB Pharmaceuticals. And I went to Belgium about a year or two ago and they held a conference with other ketogenic diet scientists to understand because they know that the diet makes their drug work better. Like you could use a quarter of the drug and get remarkable seizure control or even get completely off the drug. But I think more importantly, they're kind of fishing for understanding mechanistically the anticonvulsant effect of ketones by themselves. So as the science start to emerge, you're going to get more pharmaceutical companies interested in metabolism in general, but also specifically interested in the signaling properties of specific ketones.

Yeah, it's really interesting. You got into just there a little bit ago, some of the things that you mix with ketones to enhance deliverability. I know that, for example, you see when you look at the label of a lot of these ketone supplements, the addition of mct, you know, usually like an MCT powder. You actually forwarded over to me a study that you did that showed that the blood brain barrier was relatively impermeable to a lot of hydrophilic substances. And that would include something like ketones or ketone bodies. And so the transport of ketones across your blood brain barrier, if you do want them to be available to brain tissue, is dependent on these. I think what you described them as was proton linked monocarboxylic acid transporters, meaning that MCT powder could basically act as like a shuttle to carry ketone bodies across the blood brain barrier. So if you inject your body, or not inject your body, but consume. Right. Some supplement that has a 1, 2 combo of beta hydroxybutyrate and MCTS, you could potentially increase what's available to the brain. Now, are there other things though, in addition to mcts that you have found that one could combine ketones with to enhance their deliverability or their efficacy?

Yeah, amino acids tend to be pretty, they're good buffers, so they tend to increase the tolerability. And now we're doing the pharmacokinetic studies to see if they increase sort of the, extend out the pharmacokinetic profile, how it influences the blood levels of it. But medium chain triglycerides are really, they're awesome because they're pretty cheap. They're very ketogenic. If you give mcts as a bolus and intragastric gavage to a rat, you can achieve the level of ketosis similar to a ketone ester. And we're really blown away by that. The C8 oil is probably, you know, a little bit more ketogenic, maybe about, you know, the immediate, the regular C8, C10, you know, is about 80% of what a C8 oil would be. But you could easily get the 5 or 6 millimolar with MCTS and, and.

Then that would be something very similar to like the, like the brain octane that Dave Asprey sells.

Yep, we've, we've tested brain octane and it did really well against, you know, just the standard MCT oil by now nutrition. The Perillo brand nutrition too, they sell it in like 1 liter bottles. Was really kind of a star performer in our lab too. And so Perilla Nutrition is kind of like a small company based in Florida that sells Captree, I think is the name of the, the oil in one liter bottle. So we've used that a lot for our experiments.

I'll link to that in the show notes for people who want to look it up. So you've got like C8 type of versions of MCT oil. You also mentioned amino acids and I believe that you mentioned branch chain amino acids. Dom, I'm curious why you choose those versus like a fuller spectrum of amino acids, like essential amino acids. And the reason I ask that is because I, I tend to personally during exercise find that essential amino acids seem to give me a little bit more of a boost compared to the BCAAs. But I'm curious what your take is on that with the EAAs versus BCAAs.

Yeah, well, branched chain amino acids with leucine kind of being the more potent of them. But if you combine the, if you take a formula that's kind of a 2 to 1 to 1 ratio of branching amino acids, leucine, isoleucine and valine, the other amino acids will kind of more or less get oxidized but spare the leucine so you can get like similar leucine levels with that. So branched chain amino acids have been known for quite some time to impact anabolic pathways by activating MTOR more or less in a, in a tissue specific manner.

In skeletal muscle. And they also have or some versions of branched chain amino acids. Perhaps HMB may have anti catabolic effects.

And there's some evidence to indicate that branched chain amino acids may delay central fatigue when used in some ways. So I'm kind of a fan of that. Also Citrulline malate is something that's in a product that you know, I've used myself Xtend branch chain amino acids and they have an extend raw formula without any kind of sweeteners or anything in it that I've used myself. We've actually used it in experiments that we're doing in the lab, even cancer experiments. And we find that the ketone salts, when it's combined with branch chain amino acids allows you to continue to maintain ketosis and high level of ketosis while.

You'Re delivering occurring on a, on a physiological level that would allow the consumption of branch chain amino acids to maintain ketosis or elevate it.

Well, so leucine is, there's two purely ketogenic amino acids and one is leucine, the other is lysine and they have minimal impact, you know, glycemic response. So that's, that's one of the benefits of it.

And from a performance point of view I think that they may offer some advantages we haven't studied that. I'm always a little bit cautious to talk about things that we haven't directly studied in the lab. But there's some evidence to suggest that they may be helpful. Take an intra workout. I've taken them for years during fasting and I can tell you that they kind of help you get through periods of fasting and I believe have an anti catabolic effect. If you are fasting. You talked about also supplementing essential amino acids and I think it is important that you have essential amino acids for repair, muscle building, anabolic properties or whatever. But the meal that you ate, the steak I had venison and liver last night for my meal is kind of a heavy meal. I think those, your gut and your liver actually store amino acids and throughout probably 24 hours after you eat, especially something like a steak. And as long as you have baseline levels of those essential amino acids, they will be available for anabolic properties. Whereas the relative changes in leucine are what's most important for triggering sort of the anabolic machinery for growth and repair. And you know, you could take, you know, leucine and you, you get some above some threshold level and that activates skeletal muscle protein synthesis and but you think, you know, if the essential amino acids are not there, how's it going to rebuild? But really, I mean the meal that you ate the previous day provides availability of those essential amino acids. And you know, I tend to couple my, my workouts or exercise later in the day. So if I kind of go into it fasting, I will have a meal within a few hour time frame after unless I'm doing an extended fast. And there may be some utility in essential aminos, but that has not really been shown experimentally. But I do think.

Anecdotally from just experimenting with different fasting protocols that branched chain amino acids can have some utility there. A number of people have sent me blood work and DEXA scans and whatnot of fasting with and without branched chain. And it looks like they kept a couple pounds of lean body mass if they incorporated branch chain amino acids into their fasting, which went from three days to one guy did like 14 days. So I'm inclined to believe that they're beneficial.

I have a couple of thoughts on that. The first is that for me what I've found is that in a calorically restricted state weight and frankly dude, I walk around at about 175 pounds and my normal stable weight is about 190. So I'm constantly eating about 80% of the calories I actually want to eat to stay lean for things like obstacle course racing and triathlon and some of these other events I compete in where having that mass to Power ratio be a little bit more advantage or advantageous is a good thing. And what I've found is that when I'm doing that, typically I am doing a lot of protein restriction and caloric restriction. That's where I found something like essential amino acids to allow me to maintain muscle more effectively than branched chains. Because what I did, I interviewed Peter Attia and also spoke with him pretty extensively back when I was doing full blown ketosis for Iron Man. This was like three years ago when I was literally during the race and also in my meals and my diet leading up to the race just doing complete ketosis with zero to extremely low carbohydrates. And he recommended branched chain amino acids. There was a specific brand that he used and I'll link to the episode that I did with Peter in which we discussed this and I used the.

Branch chain amino acids.

But about eight hours into the event I bonked, I ran out of energy. And I also found that I had quite a bit of muscle loss during my training and then repeated that experiment using essential amino acids. And I actually found that having a fuller spectrum of amino acids. And again, this is probably because I wasn't doing a lot of venison and liver and meat and I was eating a relatively restricted diet from both a caloric and a protein based standpoint. I found the essential amino acids and still do find the essential amino acids to be more efficacious from a performance and a muscle maintenance standpoint than the branched chains. And that's just kind of my N equals one experience with those. But the other thing, and you mentioned this and I had kind of forgotten about this, I don't talk about this too much on the show these days, but HMB is something that you briefly mentioned a few moments ago as an active metabolite of leucine. And I know that that's been shown in multiple studies to be able to reduce muscle protein breakdown. But I'm not sure if you saw the study last year. And it was after this study came out that I started trying this combination, especially before hard workouts in a ketotic or fasted state. The combination of HMB and adenosine triphosphate. This was in the Journal of Strength and Conditioning Research and the results were substantial. They showed that through a 12 week protocol with a bunch of trained men in a double blind placebo diet controlled study, overall strength improved by more than 20% in the group supplementing with HMB and ATP compared to about 5% for the placebo group. And they also had Enormous changes in lean mass as well. I mean, the supplement group increased their lean mass by something like £20 over the 12 weeks compared to about £4 in the placebo group. So it looks like in this case, even taking something like, like leucine in isolation, combined with strength training and adequate calories and the addition in this case of ATP, they were using about 400 milligrams of ATP per day. There was a significant beneficial effect for strength, power and lean mass.

Yeah, I do think there's a lot of potential in those. I'd like to see the data kind of reproduce in multiple labs. So we have kind of an understanding how it works from a resistance training perspective to kind of like more of a CrossFit workout, to like an endurance workout. But I do think that, you know, HMB is one of those.

Is something in a toolbox that I think is, could be really helpful.

Talking with the military and going climbing to high altitude. A lot of proteolytic pathways get kicked on when you get above 14,000ft. And in formulating something for prevention or muscle sparing at altitude, HMB seems to be hitting a lot of the pathways that we think are hyperactivated in a hypoxia environment at altitude. So I think I'd say, I know I talk with a number of researchers that study this and they think where HMB shines would be a situation where the person is putting themselves in kind of an over trained state. So if you take guys and really hammer them hard and then just gym and put them through a crazy hard workout and give hmb, you're going to see an effect. But if you take like the average lifter, you know, you may not see an effect. You really have to almost put them into a catabolic state and give a relatively high dose to start seeing an effect. And the effect can be significant and I think, but I think it's context dependent. But yeah, that's an interesting effect that you saw and makes me want to look into it more and incorporate it into the formulas.

Yeah, I'm sure you have access to two essential amino acids, but if you want me to shoot you a bottle over after the call, I can send you. I also have some HMB and ATP around in the pantry too, so I can shoot some your way if you want to try that for your next massive deadlifting session.

I want to interrupt today's show to tell you about something. It's actually in my ears right now while I am recording. I have my headphones for my recording studio here on My head. And then underneath those are these little LED light emitting earbuds called the human charger. It's this light therapy device and what it does is it stimulates the photosensitive proteins on the surface of your brain using a white light that passes through your ear canals. And so this is based on the idea that the proteins are pretty similar to those found in the retina of your eye and they create a similar reaction in terms of a release of serotonin and dopamine and noradrenaline when you target these through your ear, when they get exposed to light through your ear.

It's also really good for kind of.

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We touched on things we could combine with ketones. We touched on how a ketone salt actually works and how the salt doesn't necessarily need to be just, just sodium, but could be, as you mentioned, lithium or a creatine or an amino acid or a magnesium salt. But why is it that some people, including of course Dr. Veach in that podcast that I did with him, why is it that some people believe these ketone salts to be dangerous? And also, and this is Another thing that Dr. Veach mentioned, they also believe that MCT oil, which we just talked about as being something that could enhance deliverability across the blood brain barrier, believe that to be able to block beta hydroxybutyrate absorption or utilization.

Yeah, okay, good question. So there's two questions there.

Yeah.

So why. So ketone salts have been around for quite some time, like even 60s and 70s.

So even racemic compounds, you know, like 1, 3 butanediol racemic was used back in the 1950s and through 60s and 70s, actually talked to some of those investigators who fed it at super high concentrations to humans, humans and some military studies. But getting back to the ketone salt, why they are dangerous. So I think there's a couple things that Dr. Veach may be concerned about and I'm sure he probably did research. Actually, I know he did research because I think he actually had some patents on sodium beta hydroxybutyrate a long while back and probably put it on the shelf because he was concerned about the sodium overload. So I think first and foremost, if you're trying to achieve therapeutic levels of ketosis, like for treating clinical conditions, you probably don't want to load someone up with sodium beta hydroxybutyrate. I don't think it's ideal, but there are a range of studies, one published in the Lancet actually showing that.

Even intravenous.

Pure sodium racemic beta hydroxybutyrate for a disorder. There's a number of disorders actually that's been used to. It's actually a prescription compound in Europe. One is called mad. It's called multiple acyl COA dehydrogenase deficiency syndrome. And kids that receive this are basically kept alive because they're given massive amounts of sodium DL, which is racemic beta hydroxybutyrate. And it's been used for a wide variety of disorders, even glycogen synthesis deficiency disorder. I know type three, maybe even type one and two. It's been used in various. And then I have people that actually email me some parents who have gone through exclusive channels, acquired it for their children who have various forms of epilepsy and say it's been a lifesaver because they just could not get there child to adhere to a strict ketogenic diet for some reason or another. So the balance. So unless he has data to show that scientific publication, for someone to say it's dangerous, you know, it should be backed up by science. Right. So we can't, you know, as scientists, we all have opinions, but we need to back up our data with science. So unless there's publications out there that I'm not aware of, and I've been on, you know, a number of safety committees for these things for ketone esters and whatnot. So I think he may have said that because, you know, the ketone ester that he's developed and put a lot of, a lot of thought and experiments into, it's kind of just one agent. Right. But our lab is interested in testing, you know, many different, dozens of different things and testing it against one another. And we have fed ketone salts at, you know, up to 25 grams per kilogram per day in long term feeding studies and saw no kidney. We do comprehensive metabolic panel and CBC and we see no indication of.

Liver stress or kidney stress. And then we harvest all the organs at the end and do histology and have never seen anything that would be alarming. And there's nothing in the literature, actually. It's saving the lives of many kids with different disorders. And this is actually given very large doses intravenously. So I would say the science is not there unless he's aware of something that I'm not aware of. But when it comes to the. And that's even with sodium. So I think ideally to make it even more safe, you want to balance out the mineral preparation. So there may be a conflict of interest there related to patents and accompanying products and things. And I think, you know, that could be a factor. But I think, you know, Dr. Veech believes in his heart that that the R version of beta hydroxybutyrate in the ester form is best and it could be, but it has not shaken out experimentally yet. And he may think that the sodium load, we kind of demonize sodium as being a bad thing, that that could be a bad thing, but it's not. It just doesn't show up in the clinical evidence or experimentally.

And to clarify just a few things, for those of you listening in, who don't have white lab coats on the racemic mixture that Dominique just referred to, or the racemic salts are what most of these ketone salts are. And all that means is that it includes both the D and the L configuration. So in chemistry, a D refers to Dexter, which would be like on the right, an L, I think, what is it? Laevis levis, something like that on the left. And so when we look at something that's in its D or in its L configuration, when we find beta hydroxybutyrate in its physiological form in the human body, in many cases it is in the D form, but a racemic mixture, which is what a lot of these ketone salts are, it's in both its D and its L form. And so some would theorize that because that's synthetic or non native to the human body, it might not be as good as the D form. I know that's one thing that Dr. Viets brought up. And the actual form that he developed, this ketone ester that he developed is apparently not only not a racemic mixture, but more like a non racemic mixture. And I think to his credit, Dom, I know that when you mentioned that he was experimenting with ketone salts some time ago, I think a few decades ago, he was doing research on them, I don't think he was using a racemic salt. I'm pretty sure he was using, using like, like a non racemic ketone salt. It sounds to me though, like what you're saying is unless you're seeing bodies in the streets from, you know, or, or disrupted physiology from people using these non or these racemic salts, you're saying it's, it's, it is, in your opinion.

Kind of a non issue, I believe. I mean, just based on the medical literature, you know, for treating disorders, you know, and that's published in the Lancet and the Journal of Biological Science dating back to like 1957. And you got to remember, I mean, there's the companies out there selling a lot of this stuff. I looked at some of the financials and amounts that have been sold, and it's like literally millions of doses that have been consumed, and to my knowledge, no adverse effects have been seen. And keep in mind, like A lot of animal work was done with racemic compounds. Like I have, if I look through my computer here, like I have a whole, a whole file here on just studies done with racemic beta hydroxybutyrate or ketones and showing lower oxidative stress, protects animals against hypoxia injury, protects animals against stroke, brain injury, various disorders like MAD and glycogen synthesis disorder. So across the board, you know, everything's positive, there's no, no negative things. And actually, I've contacted some of the researchers that did some work through MIT actually, and they looked at 1, 3 butanediol, which I'll talk about that a little bit more because that's actually how we make some of the ketone esters. And there was a lot of intensive work done by AFRL, the Air Force, looking at 1, 3 butanediol, which basically splits and makes 50, 50 beta hydroxybutyrate. And this was given very large doses to mice, rats, pigs, dogs. Dogs were put on a treadmill with this stuff and given 40% of their calories from that. And they showed that it could maintain their exercise performance. So it was a synthetic, they called it the most promising synthetic fuel for long duration spaceflight. And it served the purpose that it was extremely stable, it was highly energy dense.

And actually, if you incorporate it into food, it was a humectant, which kept the food moist, but it also protected the food from degradation. The big showstopper was that it tasted really bad. So it tasted pretty much like a ketone ester and 1,3 butane dial does. And that's what Dr. Veach actually makes his ketone esters from. And that's what we actually have used that as a starting material to make, to make our ketone esters too. But by itself, 1, 3 butane dial, by itself, it breaks down in the liver, it's an alcohol, a dialcohol, it breaks down the liver to beta hydroxybutyrate and the racemic form breaks down the two. So, I mean, kind of what I'm.

Saying here, you think that to use 1,3 butane dial and to market that as like a supplement for people to get into ketosis, it's simply not palatable for the general population, or are there other disadvantages?

It's not palatable. And actually, if you gavage it to rodents and actually take it yourself and then take the take like, you know, Dr. Veech's ester or a beta hydroxybutyrate monoester, the pharmacokinetic profile is pretty similar. Actually, so what the beta hydroxybutyrate monoester is that Dr. Veech has is 1, 3 butanediol. The R form with an ester bond that connects the beta hydroxybutyrate to that. And we have a diester. So we have. Our molecule is 13 butanediol with two ketones attached to acetoacetate. So the 13 butanediol breaks down to beta hydroxybutyrate, but then it releases the acetoacetate, which has effects on neuroprotection that we're interested in. But that's an ester. So, just to clarify, you know, I talked about a salt being a monovalent or divalent cation or amino acid. And ester can be. You can have an ethyl ester, you can have a methyl ester. So actually, if you have a methyl beta hydroxybutyrate, you'll get some methanol being produced. Not a good thing, but people are using it out there. I think you could have a glycerin. You could take an alcohol or, like a glyceride or a glycerol, for example, you could take glycerol and attach, you know, three beta hydroxybutyrates to it and consume it. So we have various esters like this in the lab, and we have, you know, one three butane diol mono esters and diesters. And, you know, we test them pharmacokinetically, and we also test them for different applications. But there's a variety of esters that could be made, too. Not all of them have the same potency, and not all of them are very palatable, too. So we found the most potent ester that we have in our lab tends to be the most unpalatable, too. It seems like potency is inversely correlated with palatability.

And by the way, just for the record, I took the ketone ester. That's very similar to what Dr. Veatch and I talked about. And my wife pokes fun at me because I eat anything, I'll suck down anything, and people send me supplements, and I'll just dump them straight into my mouth, and I don't really care. But I still, even with my jaded taste buds, I didn't think it tasted that bad. Just tasted.

Yeah, I don't either.

Punch, basically. Yeah.

I mean, I. You know, I've tried it, too. And I actually went to Dr. Veach's lab and tried various versions of it that he had. You know, he was actually working. He had a girl working on, you know, the different flavoring agents and stuff. And it's totally. From my perspective, you could totally dilute it out to, you know, 5, 10, and 25% to put it in a. In a bottle. That would make it, you know, potent enough to get you in high levels of ketosis. And for me, I can tolerate it, but for the average, I think it's. It'll probably be good for, like, a niche, niche market. But people out there are very picky about.

You know, taste. I mean, they're. We're not normal when it comes to taste. Like, I can drink this stuff straight, and it would put most people on the floor, like, puking, because I've seen it. I mean, people have come. Yeah, but the performance, like, you're maybe the people that listen to your podcast are a little off the spectrum in terms of what they can tolerate. But getting back to the issue. Yeah, the racemic. So there's not. There's not a whole lot of. Not any data, to my knowledge, to indicate that they would be harmful in any way. But what we want to determine is if they are optimal. Right. So that's why it's really important to test.

A lot of, you know, we'll test the various things and pick out five or six different things that are top performers and then test them all together against one another. And that's sort of the things that we're doing now. And we test a lot of things we have absolutely no intellectual property on or anything. So we approach it unbiased. Even companies that have their own intellectual property on ketone compounds, we test them in an unbiased fashion here. And I'm equally as interested in. In all things, but it does throw in, you know, when you have someone kind of negatively talking about other ketone products out there and they have, you know, patents and a company, there's a bit of a conflict of interest there. So that's why I'm kind of always careful not to put down any one. I just like to put out science, and then people can decide for themselves. But if something's dangerous and the science is out there, I'd like to see it. Just that, you know, I'm pretty much up on the science because that's kind of what I do. And racemic. Keep in mind that something like ephedrine, you know, most of the pharmaceuticals out there, you know, that we use. There was one in the history called thalidomide, I think that impacted babies. And this goes way back into the history of, you know, pharmacology. Where it caused developmental effects on the baby with racemic compound. But keep in mind, like a large majority of of drugs out there that we use on a regular basis are sitting next to me. Right here is a bottle of ephedrine. And we do some research on ephedrine for Divers Alert Network for diving. And it's racemic ephedrine. It's been used for years. Sudafed is racemic. Ibuprofen, I believe, is racemic. So there's lots of drugs out there that are racemic. Being racemic does not make it dangerous. You can't go back to one molecule of thousands in the history and say, look at that racemic compound it caused. And that's just not scientific.

I want to actually ask you in a second about that second part of the question we didn't address about beta hydroxybutyrate absorption in the presence of MCT O being inhibited. But the ephedrine, are you just using that or would folks just be using it as a decongest? I assume for diving?

Yeah. Yes. So you know it. A lot of divers use it prior to diving on enriched air. So my wife is actually in Palau right now doing research on manta rays. And she. I gave her. I traveled for the last two or three weeks. We both did. And I visited my family, and they were all sick, and I got the sniffles. So I got like, a little something. I haven't been sick in years, actually, but I got the little sniffles. And I was like, oh, I hope you don't get it. And she. She's in, you know, on the other side of the planet and has to do research under the water. And she's, you know, on nitrox, which is enriched air, and needs to get down there to do, you know, research, because she's funded to do that. And, you know, and what a lot of divers do is that they load up on Sudafed on ephedrine. So Divers Alert Network realized that this was a problem. So our lab actually studied, you know, the effects of dosing high levels of ephedrine, a CNS stimulant, to see if it would reduce the latency to seizure for CNS oxygen toxicity, which manifests itself as a grand mouth seizure. And we saw that for that to happen, you really have to take a mega dose of it. Like, you have to basically take 5 to 10 pills for you to get. And I was actually surprised. I thought it would quickly result in faster seizures, but it does increase your chances. But you really have to take lot of it. So that just came into mind because, you know, we have it on my desk here and just, you know, it's, it's the racemic compound. It reminded me that, you know, most of the many of the drugs out there that are commonly used are racemic. So we shouldn't, you know. And it's also important to notice that we have the racemase enzyme. So the L form and various tissues have different levels of this enzyme. And we're kind of looking into it, but it's even in the Human Metabolome Project, which is a public website that you can go to and see that this enzyme we have the racemase to convert to inner, convert the D to the L. And that's important. So saying it's not, you know, the natural form is incorrect because we do have the ability to convert it over to. And actually a large percentage of it does. So if you do, you know the biochemistry or the pharmacokinetics and you administer racemic compound and then look at the D and the L form, you know, what ends up happening after about 24 to 48 hours is that, you know, 80% of it is the D form and the L form just gets kind of oxidized like a fatty acid. So which is also. Which just feeds into the acetyl coa.

Yeah, that's really interesting. Yeah. And ephedra, by the way, was something that, you know, back when I was doing a, when I, when I was a bodybuilder, it was like the way to burn fat fast. And of course the alkaloids in it would cause a ton of issues with heart attack and stroke and seizures and death. And I believe that it's, I believe most of the ephedrine supplements, if I'm not mistaken, are now primarily banned in the US but it's pretty synergistic for fat loss, especially when you combine it with caffeine. I know the old bodybuilding go to for just getting shredded was ephedra, caffeine and aspirin as kind of like the three ways to lose fat extremely quickly and possibly wind up seizing next to the bench press, bench. But still.

Yeah, I think you need a really high dose of that. Yeah. You know, actually I think ephedrine has a pretty good safety profile. If you look at. It was an obesity study done, I think given up to 100 milligrams per day with the caffeine. And I think it was like, it might have been like a 52 week study. So it has a pretty good safety profile. The Problem with ephedrine is ephedrine hydrochloride is that.

You can make amphetamines kind of easy from it. And even Sudafed, you can make ephedrine, you can make amphetamines kind of easy. So I actually had to get a decongestant that I gave to my wife just to make sure she had the best decongestant. And they do sell Sudafed, but you have to go to the pharmacy and then they look at your driver's license and they give you a small amount. And it's pretty expensive and everything. So it's not. And I still think it is one of the. One of the best decongestants, you know, out there, but it's sold. I don't think you can get bedron hydrochloride. I mean, we have it in the lab because we do research and stuff. We have bottles of it, but. But I don't think you can. Yeah, you probably can't. I mean, you probably get anything overseas, but it's hard to come by. But as you said, it was a very powerful fat burner, especially when combined with caffeine. And I do have several people have. Yeah, you must be able to get it, because several people have taken it and shown me their ketone numbers. And what ephedrine and caffeine do is it mobilizes fatty acids from adipose which travel to the liver and kind of further stimulates beta oxidation of fatty acids in the liver, so their ketones tend to shoot up. And it might facilitate some glycogen depletion, too, in the liver. But you generally see almost a doubling of ketone levels in guys that are kind of training taking that. And if they keep all variables kind of equal, it stimulates their metabolism in a way that can bump up their ketone levels.

Got it.

So potential benefit of it.

Yeah. That's interesting. Yeah. The doses, I think were like about 20 to 50 milligrams. And you do that like three times a day with ephedra. But as you've alluded to. Yeah, yeah. Super easy to make speed out of it, too, if you wanted to. So there's that advantage, kids.

I used it in college, I think I never took more than 25 milligrams. And whenever I took it, I would always make sure that I would work out that day. I would never take it and not work out. And I always took one pill back when it was legal.

If you take it and you don't work out. Yeah, you're bouncing off the walls. Yeah. So what about this issue that Veech brought up about the inhibition of beta hydroxybutyra to be absorbed or utilized when taken with mct. It seems to fly in the face of what you were saying earlier about mcts enhancing delivery across the blood brain barrier.

Yeah, I would like to see that publication if that's available, but I don't think that's the case. I kind of know what he's alluding to. I mean, he's kind of theoretically saying that if you were to take medium chain triglyceride oil, you may, there's sort of a rate limitation of how these things get used in metabolic pathways and you may be restricting to some extent the utilization and the oxidation of exogenous ketones of a ketone ester. If you were to take MCT oil. But when you take mct, you make D beta hydroxybutyrate, mostly some of it may interconvert to the L if the racemase is there, but in large part you produce D beta hydroxybutyrate. So I don't know of any evidence, to my knowledge, and I'm pretty up on the publications, that taking medium chain triglyceride oil would in any way, shape or form be dangerous or block beta hydroxybutyrate. I mean, theoretically, from a metabolomic. Actually, that's an interesting. I can go back and actually look at our global metabolomic data and maybe look at the various pathways and metabolites coming off that pathway to see if that's the case. So I'm sitting on a whole bunch of data right now, and I can kind of go back and look at that. But I don't think he's, I don't think he's like citing any actual research. I think it's.

So it's basically, it's okay, it's okay to use like MCT oils and ketones together. And the MCT isn't going to like, keep you from burning the ketones, basically.

Absolutely. I actually think it's, it's optimal to do that. And, and, you know, I think mcts may be a little bit threatening to people out there with synthetic ketone products like ketone esters or even ketone salts. But MCTs in our hands are really awesome. Like in rodents, you can get levels, ketone levels up really high with medium chain triglycerides if you can tolerate them. You know, they're fantastic. Some people, I know, you know, a few people contact me if they even take a teaspoon, you know, they have like Explosive diarrhea. But I encourage them to take a half a teaspoon and try to build them, build their levels up like I can. I think I did a whole MCT experiment where I was at. After doing it for weeks to a couple months, I was, I could tolerate like 150ml a day of it. And I was staying in pretty strong ketosis just from mcts alone when I really started getting into this. And I didn't have ketone esters yet. So, yeah, I am two thumbs up for mcts. I think they're great and I think they can even further enhance the delivery and bioavailability of the ketone salts that are out there when they're formulated together.

For glycolytic performance, like I did in that obstacle course race. Have you ever tried combining the use of ketones with just straight up glucose or sugar?

You know, I get that question a lot and I see no contradiction there. And I think we've actually done quite a bit of work to show that glucose utilization is.

Increased with ketone supplementation. And we think that the combination of things going on may be an enhancement of insulin sensitivity. So I know Dr. Veach has written several reviews stating that ketones can enhance insulin sensitivity and glucose utilization. So I think the two together can be great. You know, most people out there are not going to be following a ketogenic diet, and maybe they shouldn't, you know, unless they have some underlying disorder. But I do think it is good to go keto every once in a while, whether you do it through, you know, carb restriction or intermittent fasting or whatever. But I think optimally, what may work optimally is to take some kind of slow carb together, some lower glycemic carb, or maybe in some cases a fast carb, and combine it it with ketones and deliver it intra workout, depending on the type of workout you're doing.

Most people that I know are not exercising more than an hour and a half to two hours. So in those cases, you don't need any really intra workout nutrition.

And the amount of glucose that I took and found to be incredibly efficacious. We're not talking about four gel packs an hour or what I would have used to have been doing during like an Ironman triathlon, where, well, that's what I did do was four, you know, every 15 minutes slamming a gel pack, you know, to get up to 400 calories an hour of like fructose and maltodextrin. This was 75 grams of glucose. Which is a relatively low amount of sugar taken essentially at the same time as the ketones and as the only form of glucose, the only thing going into my body calorically or supplement wise for the entire race and really the entire next six hours. So we're not talking about mainlining sugar into the body as much as possibly boosting the effects of the use of ketones with a little bit of glucose. And I found it to be like rocket fuel, honestly.

Yeah, I think we need to do some testing of ketones alone and then ketones and glucose together. And I know several people with ketone products want to do those studies and we would love to do them in our lab. And I know we did a lot of hiking over the last couple weeks and about four hours into a hike, and I drank a ketone salt product, I think it was a pruvit product, and I ate a chocolate bar. I was kind of off my ketogenic diet when I was part of my trip, so I took maybe about 25 grams of carbs in the form of, of sugar, but it was dark chocolate, so it wasn't a whole lot of sugar. And I was flying. I was, you know, we had hiked a lot already, but the last two or three hours, you know, I was heading back and I was super buzzed and was thinking about, I haven't had any kind of sugar in a while. And that combination seemed to be pretty synergistic for my energy, you know.

Yeah, the MCTs tend to slow the rate. Well, whether it's, whether it's glucose or fructose sugar molecule, there's a pretty big stabilization in blood sugar when either of those are included with mcts. I'm actually, I'm working right now with a company called Bariatrics, which does a lot of work with diabetics, et cetera. I'm trying to develop a bar right now that is a combination of something that would be like ketosis friendly, but also be something acceptable that you could use for a long hike or a bike ride or something like that. And we're actually using some pretty traced amounts of raw honey in it and finding that ketone levels stay pretty stabilized and that blood glucose really doesn't tend to fluctuate at all with that type of approach. So I think that in some cases people shy away from sugar too much when in fact it can be a pretty cool addition to an MCT or a ketotic based approach, especially for performance. So it's an interesting combination in terms of sugar remaining stable over Time from a blood standpoint. I know there was one study I looked into in the development of this and what they did was a fat spread that they enriched with medium chain. I think in this case it was a triacylglycerol. And then they added some sugars to that and found that the sugars were completely stabilized. So this is all super.

I'm not a big.

Go ahead.

Oh yeah, I was gonna say as a quote unquote keto guy, as people think I am, which I am. I mean that's kind of the cornerstone of my research. But I don't believe in sor of demonizing sugar. I think the problem is the excess consumption of sugar obviously. And that, you know, I did perfectly fine. I see my nieces and nephews, they're like sugarholics and they're, I mean they're, they're burning it up like crazy. You know, I think, you know, when we're younger we can do that, but as we age, there's sort of an age dependent decrease in our ability to use carbohydrates, you know, as we age. So it's that excess sugar and most of the people that are concerned with it are kind of athletes already. And there are people who don't have to be concerned necessarily, but at this with sugar because they're burning it real fast like you, but at the same time. But I have seen, you know, the benefits of guys that burn sugar really, really well and have no over metabolic problems, transition to burning fat and ketone and doing remarkably well. So they didn't have a preexisting problem that was overtly noticeable even from blood work, but they did remarkably well when, and I think as an athlete you have such metabolic, you know, currency with, you know, your mitochondrial health and everything that you transition very nicely into a high fat QJANK diet and quickly get your ketones levels up or start using fat for fuel very efficiently.

Right.

And in the case of my kids.

They get home and you know, yesterday they get home from school and you know, they'll have like a rice cake with honey and almond butter on it, which is essentially like a, like a little bit of a carb bomb with some nut butters and then they're out making snow forts for two hours and three degrees and I'm, I'm not concerned at all about their blood sugar levels. So one other question that I wanted to ask you was expense, right. Like we talked about, like, you know, I've heard Dave Asprey, for example, say on his podcast that when he used ketone esters. The cost of them was approximately $30,000 for a serving. And I've certainly. When the. When the keystone esters have been sent my way by some of the folks associated with Dr. Veach, you know, was informed that they were. They're incredibly expensive to make. So they wanted to ensure that when I used them, I tested and didn't just kind of pop them like candy, but instead I was pretty cognizant of their expense. Why is it that the ester would be so much more freaking expensive than a ketone salt?

Yeah, I mean, $30,000 for serving. I think someone made a lot of money off Dave. I'll sell them some ketones. I'm sure that. So, yeah, they are expensive because it's more, you know, it's more of an economy of scale thing. Right. So I needed like a little rotor rod device, like a little treadmill device that. That rats and mice run on and then automatically senses when they fall off so we can look at exercise performance. And not too many people make that device. And it was like. It was like $12,000. I mean, I could go buy a. A really nice used car for that amount. So there's not a whole lot of people making ketone esters. And I can tell you that the precursors are relatively inexpensive. There is an art, there's a science and an art to doing the transesterification to make ketone esters, whether it be a glycerol, you know, beta hydroxybutyrate triester, or a 13 butane diol monoester diester or whatever. So each one has kind of subtle nuances into developing that synthetic pathway. And you need a committed.

Organic chemist running the facility pretty much nonstop to be able to make and the kind of amounts that are needed. So it's just not cost effective for a company to do it. And once you make it, then you have to do some testing on it to ensure the potency and the purity and that you don't have leftover stuff in it like methanol or other things.

So that therein lies kind of the problem. It's an economy of scale thing. It can be scaled up to be probably as cheap as I would say, you know, $10 per liter, I think, you know, when it's maximally scaled up, I know, I think Dr. Or Dave Asprey or someone from his camp mentioned that there was formaldehyde and some of the tested in some of the ketone esters or ketone salts, rather. So I can tell you that the way ketone salts are made, like in Patrick Arnold's and the way they're made here and even the way they should be made in China is that combining beta hydroxybutyrate to, you know, these monovalent or divalent cations is relatively simple chemistry. And in no way throughout the synthetic process should you be forming formaldehyde, at least with even the cheap precursors that are available. So I don't know, I haven't seen the data on that but, but I know a lot of people have emailed me about that. Is there formaldehyde? And you know, we have some pretty good detailed chemistry analysis of at least the stuff that, you know, the companies are using like Pruvit and Patrick Arnold and Keto Sports. And there's no, you know, there's no really room and there's no way through the synthesis of these things to be making formaldehyde. So maybe it's clandestine lab in Asia or something he got a source from. But there's no formaldehyde in any of the products out there based on the synthetic chemistry. But they're expensive. I think, just to answer your question, because it needs to be scaled up. I mean, we're making it in our organic chemistry, but in little small batches. And we're making the R enantiomer and the racemic and it's much more expensive to make the R enantiomer. But if you scale it up in the right way, it could actually be dirt cheap. And that's what's kind of, you know, some people may call it heartbreaking because these compounds really do have the potential to, they have high therapeutic value for a wide range of disorders. You know, at the, at the core we're talking, you know, disorders like glucose transporter deficiency syndrome. And I'm really networked with that, with that organization. These kids, they just can't, you know, transport glucose across their blood brain barrier. And ketones can literally be a lifesaver for some of them. And there's a wide variety of inborn errors of metabolism that would be highly responsive to therapeutic ketosis in the form of a ketone ester. But these rare disorders really don't get enough attention and investors behind making it. But when you look at, on a grand scale, we also know that there are very significant performance advantages, cognitive and physical performance advantages to get from synthetic ketones. And therein lies probably the opportunity for savvy investors, forward thinking investors to say, hey.

The science behind this basically sells itself. So.

You know, it really would be good technology to invest in. And I got to say, the ketone salt products on the market, they're about one third to half as potent as the ketone esters would be. And, you know, maybe we don't want, you know, some of the ketone ester that would be too potent and too tasty because you could technically drink too much and get into ketoacidosis, not so much with the ketone minerals, because you'd probably have some GI issues and come out the other end before you reach the blood levels. That would be dangerous. But with a ketone ester, I can tell you from safety studies that we've done, you can do intragastric gavaging of a rodent and then you can slowly push them into ketosis. So for a human, you would have to drink about 700ml to 1000ml of the pure undiluted form to really get to the point where you'd be in trouble. And that would be very expensive and it would be horrible tasting. So any form of ketone ester that's going to be on the market, you're going to be, it's going to be at least a 25% dilution, which means like 25% of it is the ketone ester. And then only after that does it, you know, it becomes palatable. But typically if you see ketone esters hitting the market in liquid form, it'll probably be a 5 to 10. Then maybe the super concentrated form would be like 25% of the ketone esters and it'll be heavily flavored. And then you'd have to drink a ton of that stuff to where it's stretching your stomach to start reaching ketoacid.

Yeah, and to put that in context, I mean, ketoacidosis, we're talking about more than 20 millimolar in most cases. For something that classifies ketoacidosis, 20 days of fasting a lot of times will get you up to around 10, I mean, to just not eat anything and do a water based fast. So you would have to take copious amounts. Aside from, I don't know, if you saw this, you would throw up this anecdote. That paper, I think it was published in the Diabetic medicine Journal and there were several cases in which folks using MDMA or ecstasy combined with the excessive movements of rave dancing actually entered into a ketoacidotic state. So apparently if you use ecstasy, you might be able to get there faster. So if nothing works out for you, listening into this podcast, and you don't want to try the ketone esters or the ketone salts. It appears that you could just pop some E and go to rave for a while and potentially just get all the benefits with none of this confusion. So there you have it.

Interesting you mentioned that. We just had our. We were just. I just met with my lab folks, which are students from all different backgrounds and stuff, and we were telling kind of our stories about things like that. And I know MDMA can be a metabolic, metabolic stimulant. And if you're around people who have been taking it, you know, you get real thirsty, right. And you start kind of heating up. And one of the main side effects of too much MDA is that you start, like, basically overheating. So, yeah, that doesn't surprise me. And it kind of makes sense. Anything, any kind of metabolic stimulant will mobilize fat from adipose and you'll start making ketones. And that's, that's what you see, you know, if you give a stimulant, like even caffeine and ephedrine are a good example. You know, if you take a normal person on even a mild ketogenic diet running about 1 or 2 millimolar and keeps all variables the same and starts getting some pretty moderate to high dosing of ephedrine and caffeine. I've seen the blood work. It like, spikes right up and stays there. You know, it can double their ketone levels just. And it's a good indicator. Pretty dramatic demonstration of you kind of the. The fat burning effects.

Yeah.

Or the fat mobilizing effects. You know, you're mobilizing. And of course, like, you know, that'll probably, once you start using it, you know, you'll get that effect and then they'll attenuate over time. But I always, you know, would say that, you know, use it for two to three weeks and then get off of it for like two to three weeks and then use it again. It kind of works better if you don't use it all the time. But I've seen enough data to indicate, yeah, stimulants like MDMA and other compounds can be ketogenic in that way. We're also interested in amino acids that may enhance the liver's ability of ketogenesis. And taurine is an amino acid that can more or less help your liver make more ketones. And also, you know, I was thinking of an idea throwing it out there for me. There's some scientists that will jump on it of developing compounds that stimulate very specific enzymes in the liver.

Enzymes involved in ketogenesis. So if we could stimulate the enzymes involved in ketogenesis, we can drive our own ketone production in ways. And I think there's opportunities out there to do that that people probably start looking into. But there's an indication that Taurine given 2 grams three or four times a day can increase your body's ability to.

That's interesting. Yeah, 2 grams is a relatively high dose. I don't know much how much is in of course, red bol, but I know that's what most of the energy enhancing effects of Red Bull are attributed to is the taurine and the caffeine. Yeah, well, interestingly, one of the most well known usages for taurine back in the day. Speak of the devil. Was that ephedrine and the cramping and some of the potential, potential muscle seizing caused by ephedrine, you could reverse that with taurine. So it seems to pair quite well with central nervous system stimulants as well to kind of like knock some of the edge off of the, off of the caffeine or the CNS stimulant. But that's really interesting that it could potentially be used as something to go along with, for example, ketones and mct.

Yeah, yeah. Boosting your own body's ability to make ketones. Going back to when I was doing my postdoc up in Ohio, there was a guy in emergency medicine and he was like all about taurine. And I started looking, I didn't know much about it at all at the time, but I delved into the literature and I was like, wow, this stuff is remarkable. Maybe it's just not known because there's not a whole lot of money to be made from it or ways to patent it or whatever. But yeah, it did seem to have a lot of applications. Especially his application was like brain injury and things like that and just maintaining osmotic gradients, neurons for neurons to do that under certain conditions. I think it has a range of utility though. It's pretty cheap.

Particularly interesting.

Yeah.

I mean most of the benefits of course for physical performance, what they've found is with aerobic exercise particularly that cyclists who get taurine just have a time trial performance that goes through the roof which without an increase in rating of perceived exertion. And I know also it can interact with the Leydig cells. So I think I've also, in addition to kind of like researching how to create more of a good fat based energy bar, I've been looking into a good testosterone supplement. And one of the things I'm looking into is taurine, just because of its interaction with the Leydig cells and also its ability to reduce some oxidative stress, particularly in the nether regions. So perhaps a discussion for another day as we've been going for a while.

And I should let you go soon.

I should probably go have lunch and also take a pee soon because.

I had an enormous cup of tea before we started. I'm on this three I know I'm on this three month. It's almost like a three month detox protocol where I'm drinking copious amounts each day of licorice, marshmallow and slippery elm bark. And it just kind of. It coats your stomach and makes you feel amazing. But it also means that I'm drinking about twice as much fluid as I'm used to. So regardless though, we covered a lot of material today and I took copious notes. So for those of you listening in, all the notes are at BenGreenfieldFitness.com Dom that's BenGreenfieldFitness.com D O M if you want to hop over there. I'll link to the previous episodes with Dominique, that interview with Peter Attia. I mentioned my own article and writings about my experience with ketosis and the use of some of these ketone salts and ketone esters. I'll even embed a relatively entertaining video where I Snapchatted my use of ketone esters during that Tough Mudder event I alluded to. And I'll put plenty more in there as well. So just go to BenGreenfield Fitness.com Dom for that. And of course I'll also put a link to the original interview I did with Dr. Richard Veach about the ketone esters. So Dom, thanks for coming on the show and sharing all this stuff with us, man. You're a wealth of knowledge.

Yeah, thanks for having me.

Yeah.

Yeah. Well, you have such a far reach and I think your listeners are really a group of interesting people because many of them will email me too about questions and you always have an erudite group of listeners out there, kind of know their stuff just from listening to your podcast. Appreciate you giving me the platform to speak and I wish you all the best. And you know I'm here anytime you want to discuss any anything.

Thanks man. And I'll have to add erudite to my vernacular more often. I forgotten about that word. It's a good one. All right, for those of you listening in, thanks for listening and until next time, I'm Ben Greenfield along with Dr. Dominique D' Agostino signing out from BenGreenfieldFitness.com have a healthy week.

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Sam.