Everything You Need To Know About Ketones & Ketosis

That's one thing about ketones that I love, is that it is almost like an adaptive fuel because we have seen in. In studies with opposing effects. For example, we have seen an increase in leucine mediated MTOR activation when you take it after exercise with carbohydrate and proteins.

Leucine mediated MTOR activation. If you take ketones after exercise with carbon protein, what you mean is have like an anabolic effect.

Anabolic recovery. Yeah. And then if you look at longevity studies that has calorie restriction and ketosis, they are looking at decreasing in MTOR activation.

Right? Right. Same thing with the grail of longevity, which drives me nuts because you get all these people wasting away muscle and like you want to be like hard to kill as you age. You don't necessarily want to chase calorie restriction at all costs.

All right, folks. Well, it's probably no secret that you've heard about my experiments with ketosis, which go all the way back. Gosh. I was talking with today's podcast guest last night at dinner over some fantastic salmon. We were feasting on about how I got into this idea when I was back racing Ironman triathlon and had totally drank the Kool Aid from the Gatorade Sports Science Institute and all the research and exercise science that you. Especially for endurance exercise, you eat like a 55 to 65% ish carbohydrate based diet leading up to race week. You'd typically carb load and increase your carbohydrate intake up to like 85, up to 90% carb intake all the way up to race day and then consume anywhere from like 300 to 400 calories of different carbohydrate mixes during the race, like fructose and maltodextrin to activate different glucose transporters in the gut to really enhance your carbohydrate uptake. And that was like my jam. Up until around 2013 when I heard about this thing called ketosis. I actually ran into a researcher, his name was Dominique d', Agostino, at a conference and he had like a presentation poster that he was standing in front of. And I think it was Dr. Peter Attia, who he had on a bicycle on the poster presentation drinking what Dominique described to me as like something that had the nasty ass taste of rocket fuel. But that was like this little known macronutrient that he'd been studying for brain injuries and TBIs and concussions and some diver related injuries in the past. But he'd realized that it could be used for Endurance exercise as like this preferential fuel for the liver and diaphragm and the heart. So I thought that was interesting. And even though ketones as they are now were not really something you could just like go buy and drink, so I started to eat a high fat, low carb diet. I started to use MCT oil in my bike bottle and in my little running. What do you call them when you're a run belt, my little run bottles during the race and noticed a profound shift in endurance. And there was kind of like this side benefit of better focus during the workday. I got so enamored with the idea that I wound up being like strict nutritional ketosis for like three years, 85 to 90% fat. I did Dr. Jeff Volek's faster study where he had us doing VO2 max test and three hour long runs on a treadmill to display what at that time was groundbreaking research that by eating a high fat diet and using ketosis for performance, you could shift your fat oxidation rates, like, higher than anything they'd ever seen in research or anything you could read in the textbooks to a massive amount of grams of fat per hour burnt during exercise. So since then, I've on and off just taken different plunges into the whole realm of ketones, ketosis research, high fat diets, MCT oils and everything. And part of that culminated in me connecting with this guy who I was kind of familiar with. His name was Jeff Woo. And so I'd seen Jeff on Shark Tank before. He was selling some kind of like, energy cube supplement on Shark Tank. And then I later saw him on an airplane in a documentary about smart drugs. He was like a biohacker featured. And then Jeff and I connected at a conference and he reached out to me about this ketone that he'd been working on, developing. He sent me some. I tried it, and it was like being able to drink your way into ketosis, which was kind of cool because all of a sudden I did have to like, fast or, you know, basically tape my mouth shut every time I walked past an Italian restaurant. And I could actually drink my way into ketosis. So that was a few years ago. And since then, you know, a lot of these ketone ester and drinkable ketone companies have popped up. And Jeff's company, which is called HVMN Health via Modern Nutrition, wound up being a company that I started using for these drinkable ketone esters. Well, it turns out that Jeff wound up bringing a scientist on board for his company, and the scientist is here sitting across from me, we've already done gym and breathwork and sauna and cold and gotten up to all sorts of stuff. I was pleased to see that he actually did also have a slice of my wife's homemade sourdough bread. So he's not fully bread phobic, but his name is Dr. Lat Mansour. Lat has a PhD in physiology, anatomy and genetics from the University of Oxford. He basically has over a decade of experience in academic research, health technology, pharmaceuticals, and now oversees the scientific development and clinical application for hvmn, which has this ketone ester. If you're watching the video version of this podcast, I've got one of these ketone shots in front of me. We have this big bottle of ketones. I've got, I don't know how many ketones I've already had this morning leading up to this show. So it could, could be a really rough show or a great one, the best show ever. But anyway, so I'm definitely in nutritional ketosis right now and I believe that Lat is as well. So la, welcome to the show.

Thank you so much for the introduction. And it was, it was really interesting to hear how everyone else get to know ketosis, get to know about ketones, what are ketones to begin with. And all the way to where we are today where we have multiple companies selling drinkable ketones and you know, some misinformation out there, of course, you know, as many supplements would, would have. But that's what we're here for today. We gonna talk about ketone science, ketone metabolism and really dissect into what is the current literature that reflects the effect of ketones on brain, on heart, on performance as well as general metabolic health.

Yeah, yeah. Liver and diaphragm also from what I understand like, like most major organs, this is almost like a, like a macronutrient, like a fourth macronutrient in addition to carbs and fat and protein that you just don't see in the textbooks right now. But that is now something that you can literally eat or drink as a fuel. And when I say eat, I mean I literally made a cheesecake a couple weeks ago out of these keto bricks. Things which are like coconut butter and ketone supporting compounds in a brick. Not your guys product, but it made good cheesecake. So tell me about how you got into all this.

Sure. So I've got to start with where I'm from.

Right.

I'm from Malaysia born and bred, I guess Kansas, I know, I was gonna say New Jersey. But, you know, I thought I would be a bit truthful. I'm from Malaysia. I was brought up in a family with very high prevalence of diabetes and cardiovascular disease. In fact, my late father passed away from stroke, and before that he had a heart attack and open heart surgery. So growing up, I was also overweight as well.

So.

So, you know, for people who are listening or watching, like, I know how that feels, um, I always thought to myself that growing up, that's who I'm gonna be. You know, looking at my relative, that's how I'm gonna live my life. And I'm just gonna be heavy from young till old. Not until I was in undergrad from University of Nottingham that I started learning about biotechnology. I learned about physiology, I learned about metabolism. And then I started exercising for the first time voluntarily, because before that I hated exercise.

But leading up to that point, like, you enrolled in these science courses not because you had an interest in exercise science, you were just.

I was just interested in science. I was just a nerd. And I was a proud nerd then and now. And I learned about, in fact, my final year project at the University of Nottingham was a mathematical model of adipose tissue metabolism. And adipose tissue, as you know, is. Is fat storage, main fat storage in our bodies. So. And then I started losing weight. I lost about 45 pounds then in one year. And people were asking me was I using myself as a test subject for my thesis. And I wasn't. But I was just. I just got into exercise. I just learned more about physiology and knowing that there is something I can do to change my fate going forward. And then that sort of continued when I did my masters and from Columbia University in New York in biotechnology as well, where I really focus on drug development, pharmaceutical sciences, and learned how the, the world treat diseases, especially when it comes to chronic diseases.

Right.

And then right after my masters, I thought to myself, well, I'm not suited to be in research. I don't want to be in research. I don't want to look at test tubes every day for the rest of my life.

Is that because you're like, not introverted or you like.

Yeah, it's because I want human interaction. One I like, you know, meeting new people, learning new things, learning new languages, you know, meeting people from different cultures. But most importantly, me being a scientist, I want to have an impact on people's lives, right? Whereas being scientists, yes, you will have an impact eventually, but most scientific discoveries or investigations won't get implemented in real life until years later, because a Lot of efforts, especially with us in basic science research, meaning most of the time we are looking at mechanism of actions. In animal science, for example, we are looking at really molecular changes of, let's say, for example, how ketones affect the brain. Yeah, but so what? Right? We know the mechanism of action. Now, how does that translate to human, first and foremost, and then secondly, what are the products that can be translated into humans? So that's why I thought to myself, okay, I'm going to look for a job. And I ended up in a pharmaceutical company in New Jersey called the Medicines Company. And I was a good spot of.

The US My apologies to all the people in New Jersey, but I was.

Still living in New York. I was still living on Manhattan.

Okay.

So I did move out there. I worked there for half a year and then they promoted me into full time and moved me to Munich, Germany. So I worked there for a year. And during that year, I was so inspired by the people who are, who were there. They were so scientific. They were scientists, they all have PhDs, but they're also very entrepreneurial and they're very good at translating science into first, the language that people can understand, and secondly, translate science into applicable behavioral change that people can then take away and improve their lives.

Yeah.

So during that time, that inspired me to apply for my PhD in Oxford. So I thought to myself, well, it's a great university. If I get in, if I don't, I do like this job, I can stay in this job. And I got into University of Oxford, specializing in cardiovascular disease and diabetes. So my research was looking at the metabolism of type 2 diabetes in hypoxia, which is low oxygen environment. So I looked at the differences between fat metabolism and glucose metabolism, especially in hypoxia. What happens if you put a diabetic heart in hypoxia to those substrates? Metabolism is.

How's that relevant? I guess, like, are you referring to. Because actually I interviewed Gary Brecke and he's a biologist, lives down Miami, does a lot of biohacking and coaching for performance with some of these UFC fighters and the like. And he says that most diseases are related to low oxygenation state, mitochondrial deficiencies, and subpar metabolism that's specifically causing a hypoxic metabolic state. Now, when you're looking at a diabetic and how they operate in a state of hypoxia, I assume that's what you. The reason that you were looking at that was to see how poor oxygenation levels are affected by blood sugar issues.

So remember why I was saying I was looking at cardiovascular disease and diabetes.

Right.

So I was looking at the link between. So I'm using hypoxia as a subset of ischemia.

Cardiovascular disease causes hypoxia.

Correct.

Okay.

So when you have clotted arteries, your. Your heart is not essentially getting enough substrates going in, it's not getting oxygen going in and it's not getting all the wastage going out.

Yeah.

So as a result, you get damage to the cardiomyocytes, the cardiac cells. So my research at that time was to look at the ability of the heart to switch over to glucose to utilize more glycolysis, which we know for a fact that user doesn't use any oxygen to produce ATP. So that's a sort of makeshift mechanism to protect the heart and make sure the heart still works. And what we have found is that in diabetes, the there is way less metabolic flexibility when it comes to ability to shift over from fat to glucose. So that was my whole PhD.

Okay.

And then because of my passion in chronic diseases, I was working in, you know, health tech and diabetes management program until around 2019, where I, you know, HVMN and myself, we sort of got introduced to each other and we talked about it and they found my background very interesting, combining both the scientific background as well as the entrepreneurship in the startup world.

Did that freak you out? Some company in California, because they're based out of California, right?

Yeah.

They just randomly reached out to you?

No. So I got to know them via their previous research lead, which was Dr. Brianna Stubbs, who's a friend. So she and I graduated from the same lab in Oxford, so we only graduated two years apart from each other. And she was like, oh, HVM is looking to hire. Would you be interested? I was like, let's have a conversation. Because at that point I was still running my own company back in Malaysia. So I was like, you know, I started building this up. I'm not gonna just give up everything. Right. But then they flew me into San Francisco, really.

Talked to me, I talked to the whole team and found that their vision, and I think what drew me most to HVMN was the honesty, transparency, and scientific integrity. Yeah, they put everything behind the real data and real science, which is very rare these days, especially when it comes to marketing. Everyone will market their product as if it's the best thing that ever happened to human civilization.

Right.

But they are okay and they are willing to say, okay, this product may not be the best product. Now let's reinvent this or let's innovate. Hbma. Yeah. Is willing to say that let's innovate this with the current data we have and come up with something more useful and more efficient. And this kind of plays out to the history. And I can tell you, you know, the whole story of why we went from the first ever exogenous ketones in the market called ketone ester in 2017 to ketone IQ now, which is not the same as ketone ester.

Yeah, I definitely want to ask you about that, but I'm still curious, like, about your own personal experience with these things. Like, you told me before you hit the gym this morning that you took like, 45. What, 45 milliliters of ketones. Like, when you went out there to HP, man, were you already, like, messing around with this stuff or was this.

All new to you? So that's an interesting question, because when I was studying diabetes, all I knew about ketones. Obviously, you know, we know about bhp, we know about ketones, but that was more of a side product of metabolism. That was how I knew ketones.

You knew something the body made, not.

Something you could, like, drink, correct, some. Something that your body makes and something that could be dangerous in a diabetic individual, especially when it comes to ketoacidosis. So. But then when I joined hvmn, I did try the keto diet, but for me, it really caused more fatigue in the gym when I lift heavy. So what I'm doing now, and as you said, you know, I had a piece of sourdough bread because I am on a lower carb side, I'm not as liberal when it comes to carbs, but I'm also not strict keto, where I have, like, you know, 20 calories worth of glucose per day. So then I, you know, play around with exogenous ketones, and I realized, like you said, I can get into ketosis, get all the benefits, get the ketones into my bloodstream, into my brain, without having to conform to a strict diet, which means I can still lift heavy. I can still, you know, go about my day and be a little bit more flexible when it comes to my diet, but yet still having all the benefits of ketones. So that was when I'm, like, fully dialed in. Not only I am giving presentations around, you know, the US in conferences, talking about exogenous ketones and the literature around it, but I'm also a true believer that I, you know, walk the walk, that I actually consume ketone IQ on a daily basis, especially before podcast and before workout. Generally that's my use cases before podcast, before workout and sometimes after workout for recovery.

What's ketoacidosis?

So ketoacidosis is when you have high level of ketones in the presence of high level of glucose, especially in diabetes, because your body is not, because of the insulin resistance, you're not taking in the keto, the glucose in the blood, in the bloodstream, but at the same time the rest of your body, like your liver is also saying that, oh, you're starving because, you know, obviously all these cells are, are, are doing respiration and metabolism. So I need to break down this fat and create more ketones.

Yeah.

So you are like starving but also have abundance of, of substrate at the same time. And the increase, the sharp increase in ketones lower your blood ph. That's why it's called acidosis and that is, is what causing potentially death.

So the difference between ketoacidosis and you having ketones this morning to work out, but then also having sourdough bread, which theoretically would raise your blood glucose, is you don't have diabetes. So your body's still able to shove both the glucose and the ketones in the cells. Whereas if someone has diabetes and they have elevated ketones and elevated glucose, it's all just going to be hanging around the bloodstream causing an acidic state.

Correct.

And should it, like if somebody has diabetes, should they not use ketone esters? Like, what do you think about that?

So in that sense I would. So a few studies came out of University of British Columbia from Dr. Jonathan Little. They looked at diabetic individuals and obese individuals and they were given exogenous ketones after food. So postprandial. And they saw a lowering effect of blood glucose. Yeah, after. So I would say in terms of insurance, if your diabetes is very severe, because we know that diabetes is a spectrum, right. Either your early stage, all the way to late stage where you are just unable to take in any glucose and then your body also, you know, start creating ketones. So in that sense, I would say definitely consult your doctor before you, you take if you have diabetes. But what we have seen so far for majority of these obese and diabetic poor patients, they actually manage to lower their blood glucose because there's a minor blood glucose lowering effect when you have exogenous ketones.

I was going to ask you why that happens. Because I have been using ketones and I drink them within moderation. But then if I don't eat much food during the day and I exercise and this happened to me a couple of months ago. And then I have a bunch of ketones. In this case, I had them before dinner and we were going out to a restaurant. It was actually case in point, Italian restaurant in this case. So I knew I was about to have carbohydrates, but I had a bunch of ketones and I felt like, pale and clammy. And then I tested. I wear this continuous blood glucose monitor and I tested my blood ketones. I should test them right now, actually, because it'd be interesting because I just took a massive amount of ketones and my blood glucose was like in the 40s, so it dropped it a ton. How come ketones drop blood glucose like that?

So the exact mechanism of action, we still don't know for sure, but the hypothesis around it is that ketone gives signal to your liver to stop or lower or reduce the production of glucose via gluconeogenesis.

Okay.

Because even though we do eat glucose, and we do have glucose intake in our diet on a continuous basis.

Our liver will create glucose via gluconeogenesis as well. What people don't understand about metabolism is not as simple as when you eat something, something, and then you break it down and then you use it for energy. Yes, it does that, but it also does the opposite at the same time. Metabolism is, consists of anabolism and catabolism. So building up and breaking down at the same time is a flux. So depending on what you do, depending on your activities, you either upregulate the catabolism, which is you breaking down and creating more raw materials for you to metabolize and create energy, or. Or if you're at rest, you upregulate anabolism, where it says you're recovering, you're sleeping, you up, regulate these hormones that are related to building blocks too, so that the next day you can have more energy for it.

Okay, so basically, if you were fasting all day and then you took ketones and you found that your blood glucose dropped too low, would the trick be then just to eat carbohydrates?

Absolutely. If you start feeling unwell just because you know your glucose is way too low, then have some carbs, that's perfectly fine. What people have found is that they were very surprised that their glucose dropped about 50 points, but they don't feel unwell and they still have that energy level.

Weird thing, most of the time when I'm using ketones, it'll drop my blood glucose down in like the 60s, you know, when I'm still having a meal here. And there's. I'm not pushing myself super hard with exercise and, like, fasting too much. And compared to if I don't have high ketones or if I'm not drinking ketone esters, I feel great. Like, I don't have that blah, low energy feeling that I'd normally get if my blood glucose was too low. So within reason, it seems to allow you to be in what some might define as like a hypoglycemic or at least a lower blood glucose state and still have high levels of energy. I assume just because you, your brain, your other organs are using ketones instead of glucose as a fuel.

Speaking of which, what's your glucose level right now?

It's at 87 right now.

Okay.

But. So I just dosed. We started this podcast. I had those ketones, like, what, 20 minutes before the podcast. And I'm drinking more ketones. It's probably more ketones than.

Maybe we should have a shot.

I'll test again. Yeah, let's do another shot right now. And I'll keep testing as the podcast goes on. So what are we drinking right now? This is like a little bottle. It says ketone IQ.

Yup.

It says 10 grams of ketones. And then there's a big bottle here that's like. And I think it tastes different too. Explain to me what's in these bottles.

So it's essentially the same thing. It's just that this big bottle chest.

Excuse me, as I cough. That's bad publicity for your company that I just shoved it down the wrong throat. But nonetheless, it actually tastes way better than. Back when I was first experimenting with ketones, I was blogging. So as a blogger, people send all sorts of random products to your house, and I was getting like, these test tubes of nasty ass. Like, just tasted like drinking battery acid. And this tastes a little bit better than that. I'd say a lot better than that. What is it?

So you asking, you know, what's this big bottle, small bottle, they're essentially the same thing. The big bottle contains 10 servings of or 100 grams of RN3 butane diol.

Okay.

And the small bottles is 10 grams. So more diluted version of a single dose of that. And we can go into what is RN3 butane dial if you want. If you, you know, if people.

So the big bottle. So if this little bottle has two ounces in it.

Yeah.

And I were to drink this whole.

Bottle, I would be getting 10 grams.

10 grams. But if I were to drink 2 ounces of this big bottle, I would be getting what, like 20 grams or a lot more.

See, I don't do ounces. That's the problem. I do. I want a milliliters.

Okay. So basically the difference is that the big bottle is more concentrated.

Yeah. So that's 35 milliliter for 10 grams. And this is about 59 milliliters for 10.

But they're both called Ketone IQ.

They're both Ketone IQ. It's the same raw ingredient, is the same active ingredient in there. It's just these ones are easier for people to travel around. And it's, you know, TSA approved, so people can bring it with them if they don't want to check the luggage.

I take one on every plane, flight.

There you go.

From what I understand, I'm gonna rabbit hole a little bit here with you. So forgive me. I've heard that ketones have a DNA protective effect. Yeah, that was my reasoning due to the radiative effects and some of the stress that occurs during airline travel, combined with my ability to be able to resist the appealing yet ultimately crappy airplane food, that if I took the ketones, I would begin double whammy effect. Wouldn't need to eat airplane food or get hungry when I'm walking through the airport and pay 20 bucks for a salad. And also have the DNA protective effects. Now, the appetite session effects. I think we've already established why that works. It's replacing glucose as a bioavailable fuel. But is there something to the DNA repair idea?

So there is. There are quite some preliminary data to look at. Mitochondrial protection, especially against radiation as well. In fact, I just reviewed a grant application we're going to do. I reviewed a draft of a grant application that we're going to apply to European Space Agency to get ketone IQ to astronauts. First of all, for cognitive and physical performance, but second of all, protection against ionizing radiation. Okay, so galactic cosmic protection. I know our CEO, Michael Brand, last year at ketocon in Austin, did talk briefly about this. He sort of closed. This is like, this could be the future. So then I think a few months ago, CEO of a space company, he was a space and defense officer of eu and he reached out to us. He was like, I used your product for endurance exercise. I really loved it. I think this has potential to be used in ESA for astronauts. So let's.

What's esa?

European Space Agency. Okay, so let's look at applying for grants. So that's what we're currently doing. Fingers crossed. We'll we'll see in a couple of months or next year. Usually this grant processes, you know, take a while, but that's one of our current grant application that we have in the pipeline.

Cosmic galactic protection. You just sell that idea to Elon Musk.

I know, I know. If Elon Musk is listening to this, you know, it's about time to send.

Some ketones IQ out there listens every episode. I won't stop blowing up my phone with questions. Okay, so the, the label on this stuff says one three butane dial.

Yes.

Now, my limited amount of experience in the past with ketones, when I would try them or they get sent to my house or whatever, you'd always see beta hydroxybutyrate like bhb. Correct. And then sometimes you'd have, from what I understand, you could probably explain it better than me. You'd have like a ketone ester, which is beta hydroxybutyrate bonded via some kind of an ester bond to R13 butane Diol.

That's correct.

And then yours just says, it doesn't say beta hydroxybutyrate at all. It just says R13 butane diol. So how come this is different?

So let's take a step back and just explain what ketones are. Right. So as you were saying earlier, our bodies evolutionarily is designed to create and metabolize ketones. The three main form of ketone bodies that we produce are acetoacetate, acetone and beta hydroxybutyrate. Bhb.

Okay.

BHB is the main form of ketones that, that we use to circulate within our body because it's in a stable form and it's also being metabolized for energy. So there is something that called free BHP acid, which is a BHP powder that is a supplement that people can take directly. So it's taking in BHP directly. The problem with that is that it is in acid form. So it's like drinking acid.

Right?

You're going to get acid reflux, you're going to get, get GI issues. So people can't get too much of that. So what happens is then 20 years ago DARPA funded NIH to look at what is a potential super fuel that military can use to power their soldiers for long and demanding missions. You know, we know carbs, we know proteins, we know fats, but is there something else out there? That was when they were toying around with the idea of exogenous ketones.

Okay.

And as a result, they came up with ketone ester because, you know, free BHB is too acidic. So they bound a BHB to butanediol. What does butanediol do? Butanediol goes into your liver, gets converted directly into bhb. So what happens when you drink ketone ester is that when you drink it in the gut, the esterase cut the ester bond. So the BHB goes directly to your blood, the bdo butanediol goes to your liver, gets converted into BHP in slow releasing form. So that was what HVMM brought into the market in 2017. That was the first ever ketone estate.

Was the ketone ester, the BHB bound to the 1, 3 butane dial. That was like your first product?

Yes.

Okay.

So that was the first ever ketone ester got to the market. And that was also the first product that manages to raise blood ketone levels up to 3 to 5 millimolar before.

That, which for people who might not understand 3 to 5 millimolar, from what I understand, usually once you cross about 1 millimolar, you're kind of sort of starting to get into ketosis.

And then once you get above 3 millimolar, you feel really good and super stable. And then correct me if I'm wrong, once you get above like 7, that's where you start to risk, like getting too much ketones or almost like ketoacidosis. That.

That is correct.

So.

So with the current data we have, we used to think three and above is good. We used to think that. But with the current data that we have, we are looking at anything. It's so ketosis, nutritional ketosis is defined by anything above 0.5. But from a therapeutic point of view, a lot of these studies using ketones for either epilepsy or Alzheimer's or cardiovascular disease or diabetes, anything above 1 millimolar is considered a therapeutic zone. Anything.

So the difference is nutritional versus therapeutic.

Okay, that's what, that's the loose term that people are using at the moment. And then for performance, we are sort of looking at between 1.5 to 2.5. Anything more than 3, you are going into a acidification of your blood and lowering of the ph. Already not so much in the ketoacidosis realm, but still you are getting your blood to be more acidic. And one study actually came out stating that because of the acidification of the blood, they are upregulating all the cardiorespiratory stress biomarkers, that is your heart rate, your breathing rate, because they are trying to expel the carbon dioxide out to neutralize the blood ph.

So more isn't necessarily better.

Exactly. And these people are also having higher.

Perception of. Sorry. Higher rpe. So perceived. Sorry.

Rating of perceived exertion during exercise.

Exactly. So they feel like they're working harder.

You feel like you're working harder. Now, I think it's going to vary from person to person. Right. Because if you're, let's say fat adapted, you've been restricting carbohydrates moderately or you've been using a lot of ketone esters, you might be able to better utilize ketones. And so the amount of ketones, let's say drinkable ketones, that shifts you into like three plus millimolar, your fat adapted marathon racing friend. That amount might only put them at like one and a half millimolar.

Correct.

So based on that, it seems to me it would be pretty prudent if you're messing around with this stuff from the early time that you start experimenting with it to perhaps measure your ketones and kind of see what amount would be shifting into what. Millimolar, that is Ketones.

Yeah.

What do you use to measure ketones?

I use either keto mojo, like the meter, the blood ketone. Keto mojo or the Abbott Precision extra.

Those are both blood.

Those are both. I usually would go for blood because blood measurement would measure your blood ketone levels, which is usually bhb. There are devices out there which measure breath, in which case you are measuring acetone, and then urine, in which case you're measuring acetoacetate.

Okay.

Those two are somewhat correlated with blood ketone levels, that is blood bhb, but not accurately. Because sometimes what happens is when you are on a ketogenic diet over a period of time and you're very keto adapted, the amount of acetoacetate that you are going to be peeing out will be less because your body is more efficient at converting it back to bhp.

It's not going to give you an accurate value.

Correct. So I always go for blood. But then again, you know, some people can't prick their own finger and they just can't send the blood or whatnot. But I, you know, when we did our internal study, because we obviously have to know this product like inside out, I had to prick myself seven times in the span of six hours in order to look at my blood ketone levels going up and going down after certain doses.

Oh, you poor baby. Finger. Finger must have been bleeding all over the place.

I know, I ran out of fingers.

Okay, so Back to your story. DARPA funds this trial and dumps millions of dollars into whether ketone ester would fuel their super soldiers or whatever for a long period of time. You guys, though, after launching this ketone ester, based on, I assume, some of the research they'd done and that you'd done, didn't wind up continuing down the path of this.

So in 2017, we actually started a STTR Phase 1, 1, Phase 1 trial with SOCOM Special Command. And we looked at the decline in cognition in hypoxia, and that decline was mitigated with ketone ester. And that was enough for SOCOM to say, here's $6 million. It's a contract from DOD and SOCOM. Why don't you guys do a phase two study where we look at way more expansive tasks that looked at military and high and hypoxia and ketone ester, which is. Which I'm the principal investigator of. So I am currently overseeing the $6 million grant or contract that looked at ketone ester in cognitive and physical performance in hypoxia.

Okay, so why do you start using the dial instead of the ester?

Exactly. So because of pandemic, this study has been prolonged way longer than it's supposed to.

Right.

Because of COVID Because of COVID because of the recruitment, because we can't recruit, like, you know, people to. Because it's. It's clinical trial. Right. So everything was shut down, and we had to have a non. No, no cost extension. So it's sort of prolonged. So during that time, more and more studies and more data came out. Right. Like I said earlier, the acidification of the blood. That paper came out, um, a lot of other conflicting studies came out that ketone Esther may not improve performance, but just make you feel like you're working harder, like rpe, increased rate of perceived exertion. So we feel that, you know, on top of ketone ester being super expensive.

That was about 25 grams for about 30, $40.

25 grams for 30, $40.

This is 25 grams for $10. Oh, okay. So that's.

Price point is this little. How much is in this?

That's 10 grams.

So 10 grams. This little bottle will be how much?

That's for $5. I believe that's. We are. We're available nationwide in sprouts as well. So people can go there. The first shot is on us. So if you go there, get your first shot, you scan the QR code, and we'll give you a refund so that everyone can try this because we do believe in the product so much that we know that you will feel the subjective difference.

That's cool.

Yeah.

Okay, so you've got the diol. And what'd you find out once you started using a diol instead of an ester?

So we found that the increase in blood BHB is very smooth and very slow and steady instead of a spike, because as I said earlier, for ketone ester, it enters your gut. The asterisk, cut it into half. The BHB goes directly into your blood. So you don't have a mechanism at which you can gatekeep how much BHB you're getting with butane dial. Your liver is the gatekeeper because your liver is getting all the signals from the rest of your body, how much fuel you have in your body. So it is actually regulating how much BHB is releasing or converting from bdo. So this is very apparent in our internal study where we use all the way up to 0.8 to 1 gram per kilogram of body weight. And that translates to about 80 grams in one bolus. I've taken 80 grams of this and my blood BHP will not go further, further higher than 2.5 millimeters.

How do you feel when you take 80 grams?

Not good. To be honest. I do not recommend anyone to take 80 grams at this at one time, even when you're working out. That was just for a clinical study for safety and tolerability. I just feel sleepy, to be honest. And it's not something we recommend. So what we Normally recommend is one dose is 10 grams. Or if you're working out, you know, you could go up to 20 grams, depending on your body weight. But most importantly, what I wanted to point out is that the really slow increase in blood BHB gives people the larger amount of time where people are spending in ketosis. So that's the third point as to why we switch to dial.

So.

So first, you know, is the pharmacokinetics. The. The second is the price point. Uh, and third is the. The taste. So, so the pharmacokinetics is what I just described. And then the taste of ketones, you've tasted it, it still tastes really horrible. One of the tasks that we had to do with the military $6 million contract was to improve the taste. And we worked in conjunction with Monell Research center, and they're the experts in sensory Research Center. Then they are very good at pinpointing, like, what causes a bad taste and how to remedy that. Either they they block the receptor or they use a receptor antagonist or they use a bitter blocker, whatever. They've done everything they could and the results came out. Instead of any sweeteners, both natural and artificial, decreasing the bitterness of ketoneaster. The ketoneaster actually managed to decrease the sweetness of these superficial and natural sweeteners.

Geez.

Which is horrible.

Cosmic galactic superpowers. I don't think it's that bad if you mix it with like some sparkling water and some stevia. Like I've messed around with the esters and like if you, if you dilute it, it's, it's not half bad.

It's diluted.

I like that you can drink these straight out of the bottle. Even this concentrate one, like this big bottle, like it's, it's a little bit more like syrupy ketone tasting like, not syrupy sweet, just like a thicker, almost like a slightly bitter taste. But again, it's not that bad. I actually do a shot now. I do a little bit more. I do like 45 to 60 at lunchtime because it just like I don't have to eat again till dinner.

Right.

That's my problems. I have a raging appetite. So I've used this as a hack to just like keep me going from lunch to dinner in a state of hyper productivity without actually having to, you know, grab some chocolate covered almonds.

I usually prefer the bigger bottle because it's easier for me to dose higher than 10 grams if I want to.

Right. Because I'd have to dump two of these bottles.

Right. I'll have to open multiple bottles, pour.

It in bone broth or sparkling water. So related to the sleepiness thing with the higher amount that you took like the 80 grams, this is something that's obviously getting talked about right now is if it stimulates the effects of alcohol. Because there's the companies that I'm sure you're aware of, like Keto hall or Ketone Aid, they have the drink that's supposed to simulate a Moscow Mule or a gin and tonic or whatever with the idea. And I think that's one three butane dial also that it would make you kind of sleepy or give you like the socially lubricating effects of alcohol. Is that because it's like a super high dose?

I think if you really go super high dose, I don't think it's like similar to alcohol because you don't get hangover from it. You don't. But again it falls down to the dosing.

Right.

If you look at science, anything at really High dose, you're going to feel ill. Even glucose. If you overdose on glucose, you will start puking because your body just rejects it. Right. So if you look at their product, their alcohol product has 12, 12.5 grams of butane dial.

Right. And if I drink like two of those, which I guess would be like 25 grams, I'll feel like a little bit like loosey goosey.

But if they are just publishing that 1 serving, 12.5 gram is equivalent to alcohol. And they also have a ketone ester product that is 30 grams of ketone ester, half of which is butane dial. Now, I might.

But their ketone ester one, it says that's like 12 servings in a bottle. It's a very small bottle, but they say it's like 12 servings and you're supposed to take a tiny amount.

Yeah, but before this, they would publish that, you know, 30 grams minimum for one serving.

Oh, wow.

Yeah, because that's what the studies have been doing.

Right.

All the Studies that use 0.5 gram per kilogram of body weight, they use at least 30 grams or 25 to 30 grams of ketone ester, half of which is butane dial. I may not have a Ph.D. in mathematics, but if you, you know, divide 30 by half.

Yeah.

Roughly, it's about 15 grams.

If you're going that recommendation, drink the whole bottle.

Right.

Yeah.

And 15 grams is butane dial. And you. And these are the products that showed improvement in performance. Now I'm going to argue how can you have something that contains Butane dial, about 15 grams, increased performance, but then something that's lower in butane dial, 12.5 grams. You are stimulating alcohol effect to me. Either they are spiking something into that 12.5 grams in which they should be transparent about it. It's like that's not the butane dial that's causing the effect. It's whatever you're adding in there that's causing the effect. Or you don't have scientific integrity and actually lying and spreading misinformation.

Yeah, I think like 12.5 grams. I don't notice that there's definitely appetite satiating effect. But if I get up closer to like that 30 gram range, like if I were to drink a couple bottles, I'll notice like a little bit of a relaxing feeling. And I'm wondering how much of that is due to potentially the hypoglycemic effect. Like, do you think that one of the reasons, like, let's. Because we know exercise just naturally raises blood Glucose. Right. Because you're exercising and your liver is starting to break down glycogen and your muscles are starting to break down glycogen. So it's pretty rare if you're out exercising that you're going to get hypoglycemic on ketones. But maybe if you're just like sitting around in the evening drinking a bunch of ketones, I'm wondering if part of it might be the hypoglycemic effect that would cause you to feel like you've had some alcohol.

It could be. But also I think we do know that ketones do act upon the Galba regic pathway where it does have a enzylytic properties.

So it does relax GABAergic, meaning that the GABA. GABA gamma aminobutyric acid, the inhibitory neurotransmitter.

Yeah, so it does have.

That's so interesting because we were actually talking before the podcast, like the ultra running community, right. They'll use THC before they go out and run. And if I were to use THC and I'm sitting around a bunch of friends at dinner or watching TV or something, I actually get kind of sleepy. And I've done this before, like I've taken 5 grams of THC and gone and exercised. And I'm not necessarily endorsing using weed as a performance aid, even though it seems to work surprisingly well in the ultra running community along with lsd, which I recently learned actually increases beta oxidation, which is one of the reasons why LSD plus THC is like the ultimate stack for ultra running. And again, proceed with caution folks, like be responsible. But I'm wondering if part of it is the context too. Like you're out exercising, you have high ketones and you're in this performance state. And then if you do the same thing and you're sitting around with your friends at night having food, maybe it has more of a relaxing effect. Like, I don't know.

Yeah, I mean that's what I think. That's one thing about ketones that I love is that it's almost like an adaptive fuel because we have seen in studies with opposing effects, for example, we have seen an increase in leucine mediated MTOR activation when you take it after exercise with carbohydrate and proteins.

Leucine mediated MTOR activation, if you take ketones after exercise with carbohydrate protein, what you mean is have like an anabolic effect.

Anabolic recovery. Yeah. And then if you look at longevity studies that has calorie restriction and ketosis, they are looking at decreasing in MTOR activation.

Right, right. Same thing with the grail of longevity, which drives me nuts because you get all these people wasting away muscle. I'm like, you want to be like hard to kill as you age. You don't necessarily want to chase calorie restriction at all costs. Yeah.

And we can talk about all about like increasing muscle mass, you know, for brain health and strength. We talk about. I talked about this at length with Dr. Tommy Wood, which who you are very familiar with. Yeah, yeah. So, and then another example I'm going to give you is appetite suppression.

Right.

We have seen what you call it, appetite suppression.

Oh, appetite.

Appetite suppression. So we have seen ketone ester decrease in ghrelin. We know RN3 butane specifically.

Ghrelin is the hormone that would make you hungry.

Yes, correct. And RN3 butanediol specifically has leptin synthesizing effect. So leptin is the other hormone that makes you feel full.

Yeah.

So but then at the same time, you look at a study by Peter Haspel that looked at overreaching symptoms and recovery. They had ketones 30 minutes after workout, 30 minutes before bed, three weeks later they have an increase in 15% of output power output, and that is corresponding with an increased consumption of calories.

So if appetite suppression is supposed to be there, why are these people eating more and therefore provide and therefore producing more power? So that's what's interesting to me. It's almost like you have ketones and it's doing whatever stimulus you provide your body.

That's kind of cool. Yeah. Like it shifts you into a better adaptive. It sounds like, like horrific, like over the top marketing. But what you've just described is my personal experience and it's been kind of confusing to me.

It kind of helps me out the way that you explain it as like an adaptogen, like reishi mushroom, it'll relax me if I'm ready for a nap and ready to settle down. And yet if I need some energy, like using adaptogens for energy seems to shift me the other way with the idea that adaptogens might increase cortisol if you need more energy and decrease it if you need to rest. That's interesting that ketone might work as an adaptogen.

And there are some questions from our co customers as well. They're like, okay, you claim that this gives you calm energy. How can you claim that it gives you calm energy, but at the same time you can claim that it gives you bigger performance or better performance it's exactly because of that.

It's.

You can still have the energy but you're not jittery like a stimulant, like your caffeine would do to you.

Yeah.

You know another example also inflammation. We know for a fact that ketones reduce inflammation. It has direct effect on NLRP 4 free inflammasome. Right. So it decreases inflammation. But get this, when they took, when they looked at in vitro, which is, you know, in the test tube, and they in, they put bacterial toxin in it and they put ketones in it, inflammation went up.

So when there is an invasion, you want inflammation to go up. But when ketones are present, inflammation is higher than without ketones. So that's super interesting to me.

Yeah. What about for sleep? Because again, it's like the performance thing because I've taken it before sleep and I've found. I'm curious to hear your thoughts on this. If I take like a moderate amount, like I guess what you might consider like a low to moderate amount of ketones before sleep, I get better sleep. And then if I take a lot of ketones before sleep, it's kind of like if you drink a lot of alcohol before sleep, like you kind of fall asleep, but you don't get great sleep.

I see. So for we, we did try, we did look at sleep and hrv, so far we did not see any significant difference between placebo and ketones. But what I can say anecdotally, like you said, some people rave about the effect of ketone IQ and sleep. They got better sleep performance and some people, they find that they have way more vivid dreams as well. So I think with regards to sleep, there's still more research that needs to be done before we can claim anything on that. And I think right now people are just using it anecdotally and from case by case basis.

When I took my freediving course, I experimented with and without ketones before we did our breath hold practice and freediving. I think I was telling you this. Last night I had over 40 extra seconds on breath. Hold on, exhale after dosing with ketones. Is that because of the modulation of hypoxia or how exactly is that working?

This is super interesting. What you just said just reaffirmed what we have seen in our military project because we simulated 14,000 to 20,000ft altitude of hypoxia and hypoxic chamber. And what we have seen is that with exogenous ketones, the saturation, not a hyperbaric chamber, hypoxic chamber, hypoxic chamber, the oxygen saturation decreased from about 99, you know, 100 to about 65%.

Pretty significant.

But if you have exogenous ketones, they only drop to 72%. So there's a 7% increase in oxygen saturation and that is reflected onto reaction time, vigilance, cognitive benefits, all of that. And we are in the middle of writing the manuscript to be published. So I am so excited with this, with this study, because we've got seven tasks in total, so we have at least three to four papers that is, you know, we're using a mask, we're using a hypoxic chamber. And also we followed the 10th special group into the mountains where they did their mountaineering course and have them on keys on the. Measure their biomarkers and measure the performance and ask them to do cognitive test tests and look at how they did after having ketones as well.

So is that less glucose metabolism, therefore less lactic acid, therefore less need for oxygen buffering that that would occur?

Mechanistically, we didn't measure because it's very difficult to measure mechanism mechanistically when you're already in the mountains and all that and draw blood. I would say when you're in hypoxia, for. For a fact that you are activating the hif, which is hypoxic inducible factor, which is, you know, direct effect onto your DNA, so that you can start expressing all the enzymes and hormones that is related to hypoxia or hypoxic survivability. So one of the things that get up regulated is glycolysis, which is glucose metabolism. Right. But with ketones, for some reason, it's increasing the amount of oxygen that you're able to carry. Carry that may not directly be attributed to substrate metabolism per se, but it could do something. It could be due to something around the mitochondrial efficiency.

Interesting.

So that's. I spoke briefly with.

Another scientist who worked with Richard Reach, who was involved in the original DARPA research, and he.

He's kind of like the Godfather ketone research.

Right? Exactly. So he said it's something to do with mitochondrial and the different complexes and superoxide conversion and all of that.

Interesting. Okay. By the way, my blood glucose right now is at 78, so it's dropped nine points since we started because I was at 87 when we started. And before that? Well, I peaked out on the walk this morning at like 100, and it's a steady decline since then. I've pretty much been dosing with ketones Every, you know, all morning. So it's dropped. We have been just sipping ketones, 23 points so far this morning. And I'm not exercising, I'm just sitting here. So that's interesting. I'll keep measuring it as we go because I'm still drinking ketones. I'm just, I'm thinking about just continuing to dose as we go as a kind of experiment here.

So to the exercise piece. Like I mentioned, early on in the Ironman days I was experimenting with ketosis and all I had available to me was MCT oil because a lot of these ketones were very expensive. And so initially I was mixing MCT oil with a small amount of carbohydrate, like one quarter of the amount of carbohydrate that I normally use. Initially I was using this stuff called ucan. The problem is that it's a very resistant starch, even though it results in a slow release of blood glucose into the fuel. Sipping that over 10 hours of an Ironman triathlon, the fermentation and bloating by the end of the race is horrific. It literally looked like I was pregnant by the end of the race. And maybe it's because I just have trouble breaking down resistance starch. I don't. And it's still the case for me. Like if I have a lot of those, like green banana starches or cooked in cooled rice or anything like that, I get horrible gas. It might just be my GI system, but the you can didn't work for me. So I found that a longer chain starch glycofuse was one that I was using. Vitargo is another. These are longer chain potato based starches, like way longer than maltodextrin. I found that by using about 1/4 of the recommended dose of that, so around 100 calories per hour. And to contextualize that for people, a lot of recommendations for a guy my size would be 300 to 400 calories of carbohydrate per hour. So I was doing one quarter of that for getting a little bit of the slow bleed of glucose into the system. And then I was combining that with electrolytes and with amino acids. Now, early on in my racing days, I had a lot of conversations with Dr. Peter Attia and he highly recommended to me if I was going this ketosis root to use branched chain amino acids as an alternative fuel. I later started to use essential amino acids because I found those to be superior. And that might sound like the fox garden, the hen house, because I have a company that Sells essential amino acids, but nonetheless, like, they worked for me. That's actually one of the reasons that I began selling them at my company, Kion, was because I was using them so much in my own racing and using them with all my clients, my athletes. So basically in my water bottle and then in my little run bottles on the run belt for the marathon, I had, in the case of the run bottle, very thick mix in the water bottle for the bike, a diluted mix of MCT oil, essential amino acids, a long chain starch, but in low amounts, and then electrolytes. Later, when I got my hands on ketones, I simply replaced the MCT oil with the ketones. And that was just the most fantastic fuel ever for Ironman. Like I could just go and go and go. And the way that I raced is when I got to the point in the race where I knew that I could go anaerobic, and this was just based on testing, I knew that with about 10 to 13 miles left in the Ironman, at that point I could pull the parachute cord and shift into glycolysis, turn up my intensity and go at full steam to the finish line wine. At that point I switched to just drinking Coca Cola from the aid station, Just pure sugar. So I'm like, okay, shifting to pure glycolysis now. I've spared glycogen this long in the race, so now I can shift to glucose. And the stuff that's in coke, really fructose as a fuel, plus the caffeine and the coldness and like the comfort food taste of the coke, it just strings you through that, even with a carbonated. Yeah, well, no, it's flat coke. Sorry, it's flat coke at the aid stations. So. So anyways, that was my jam for Ironman and then it worked fantastically, by the way. And I'm still surprised, at least to my knowledge, that no company has come out with like a powdered mix of like some kind of ketone or MCT with a high molecular weight starch, with electrolytes with essential amino acids because it's the most amazing endurance fuel I've ever discovered. But to my knowledge, like I was doing, you still have to kind of mix that all up yourself in the kitchen. I would literally have a blender blend it all and pour it into my water bottle.

I think a lot comes with the body weight match data as well, because, you know, if you have everything already blended, then let's say if you have to increase the ketone dosage, then you have to take more. But Then you're also increasing the other.

Based on what we talked about before in terms of ketone sensitivity and you don't want to shove yourself over 3 millimolar ideally. It's a good point.

Right.

So anyways.

The thing that happened was later on when I got out of endurance racing and got into a sport that's more anaerobic plus aerobic, namely obstacle course racing in a tough mudder, I thought, well, gosh, why don't I increase the levels of both substrates simultaneously elevate my ketone values and my glucose values, which I think, as you noted earlier, could be like an unnatural state for the body to be in. But an amazing performance hack. Right? Elevated blood glucose and elevated ketones crushed the tough mudder, won the race by a country mile and felt like I was on rocket fuel the whole time by mixing gels like fructose melt induction drills with ketones. And then I was like, oh, this could be used for like what might be considered anaerobic performance as well. Not necessarily like a full on like 32nd all out sprint, but carrying sandbags, climbing ropes, you know, hauling over obstacles and then running aerobically and then going anaerobic again and back and forth worked fantastically for that. Now my question for you is that I saw before our podcast that there was some new research out on ketones related to anaerobic performance when traditionally they've only been associated with aerobic performance. So explain to me what's going on now with ketones and anaerobic performance. Yep.

So first and foremost, because ketones are so much more related to fats, because fats break broken, you know, gets broken down into ketones and then we metabolize it. Right. So then automatically we are thinking that, okay, it must be good, better for endurance, because for endurance we want to tap into that fat. Like you said earlier, rer, you want to the rer to go towards fat metabolism instead of glucose because glucose will always be king when it comes to anaerobic because glycolysis gives you that fast ATP without even having to use any oxygen.

Right?

Right. So that's why nobody has been has done anaerobic performance on ketones. But then we decided, you know, hvmn, as usual, we do some crazy things. We do things that no one wants to do and let's see what the science says. And we partnered with University of North Georgia, one of the best military college in the US to look at effect on ketone IQ with carbs in anaerobic performance. So what we have done is that we put participants 18 to 24 year olds on a 5k run. Immediately after the 5k run, we put them on a stationary bike ergometer and they go. They went through the anaerobic Wingate test. So for those.

You guys are cruel.

I know.

Explain the Wingate test to people because, I mean, 5K is tough, but Wingate's really tough.

Yes. So Wingate. So these participants have to go through five bouts of 10 second sprints on that bike at 7.5% body weight as a load, as a resistance, 7.5% of the body weight.

I'd have 150 watts.

Something like that.

Yeah. Wait, was that, was that the wattage or was that.

It's a resistance.

That was the resistance.

That was a resistance. So then, so then during that five bouts, they have 10 second sprint, 30 seconds rest. 10 seconds sprints, 30 seconds rest five times.

Right.

And they got their ketones measured. They got. So they had ketones before the 5k run and then topped up after the 5k run. Okay, okay.

But after the run. But before the Wingate.

Yes, okay, Correct. And they had. So we just submitted this paper.

You hear that crinkling, by the way? I'm opening up another ketone. Oh.

Oh, you want one, are you? Well, yeah, sure. Why not?

Here, Cheers. Then keep going on this test.

Yes.

Yeah, let's do another one. So I'm going to figure out what my upper. This is going to be more ketones than a I've ever had in my life in one sitting and be definitely more than I've ever had on a podcast.

Wow.

But I'm doing this because I want.

To keep track of. Let's see how I want to keep.

Track of the blood glucose too, as we're going here and just see what happens. All right. Cheers.

How smooth you are. And.

All right, so.

So during this Wingate test, you know, they, they, they were asked to go as fast as hard as possible.

Right.

And we just submitted this manuscript to Frontiers in Physiology and they're under review right now.

Okay.

And we saw increase in average power.

Peak power and velocity. So not only these people are paddling harder, they're also paddling faster. And on top of that, we also measure fatigue levels because as you go through that five bouts of exercise, you are inevitably going to be more and more fatigued.

Yeah.

People who are on ketone, IQ and carbs, they experience less fatigue than those on placebo.

Now, I would hypothesize that part of this would be due to the glycogen sparing effect that occurred during the 5K run, meaning you're burning less glucose during the 5K run. Is there anything else going on there? Like, had you ever thought about doing just the wingate without the 5k run, for example?

Great question, great question. And I did ask that. So the reason why we did the 5k run is because a lot of the studies, a lot of other studies also did that 5k run, and they saw no, no difference. And we want to sort of replicate that to build on top of that, because otherwise other scientists would just scrutinize the paper and say, you know, no one has done this. No, you can't. You can't compare to anyone. So that's the reason we did the 5k. So the next step is definitely better to do just the anaerobic and see what's the difference. And during the 5k run, you were right. We did measure the RER, and people on ketone IQ and carbs have significantly lower RER, meaning they are burning more fat than glucose. So in the placebo group or glucose only group, we are looking at about 0.94 RER, whereas the ketone IQ and carb group, we are looking at 0.86, 0.89.

Okay. RER, by the way, for those of you listening, is a respiratory exchange ratio. It's indicative of the amount of carbohydrates compared to fat that you're burning. Higher RER means more carbs, less fat. Lower RER means more fat, less carbs that you're burning.

Yes. Okay, so they're burning more carbs, and that is expected. And as you said, it could be the glycogen sparing effect. And also because we measure the level of blood ketones before the 5k and after the 5k, and we saw a decrease in the ketone. So together with the RER plus the decrease in ketone levels, we can assume or we can, you know, insinuate that these people are burning the ketones, oxidizing the ketones as well. However, we are not sure if the ketones are being burned in skeletal muscles, in your heart, or just simply lost via acetone in the breath. Okay, so that's, you know, whoever who's listening in terms of researchers, that's the next step we got to go to measure. Right, like, what are we measuring? What are we looking at? Muscle biopsy, you know, then we can look at really the glycogen sparing effect.

What about, what about the brain? Like, is there anything going on in the brain?

I was Just about to say that. So. So the next reason that we think that could be why these people are performing much better at anaerobic exercise is not simply the glycogen sparing effect, because this could have a potential analgesic effect on the brain. So basically it's a pain tolerance increase after taking ketone, IQ and carbs during this, because the whole wingate test is meant to elicit a huge shift in ph, I. E, lowering the pH, increasing lactic acid buildup, and having excruciating physical pain and possibly vomiting.

You know, and pain in these sort of like target muscle groups. So having said that, if people are able to push through that, push harder and faster, and feeling fatigue less.

Then it could possibly having a direct effect on the perception of pain itself. Now, if you compare this to ketone ester, it may not be a good combination because anaerobic itself, like I said, it's meant to elicit a huge shift of ph. And ketone ester on its own is able to already drop ph so much.

Accelerate that PH shift.

Yeah. That people might just feel really awful. And coupled with the bad taste, they might actually have GI issue, which could also lead to an overall decrease in performance in the stimulus, which a lot of studies have showed. The drop in performance is because people started vomiting, started not feeling well in general.

Now, one of the reasons that you see kind of like a shift in focus sometimes after you work out is I think in some scenarios, probably due to an increase in blood ketones due to potentially glycogen exhaustion or increased fat utilization. But then there's also this idea that in addition to ketones being one of the preferential sources of fuel for the brain, lactate is another. And you see lactate crossing the blood brain barrier and being used as an alternative fuel to glucose for the brain. Now, based on that, is there something to be said for what might be occurring from a lactate standpoint here for the brain?

Is there any studies you guys have done on lactate as related to neural performance or anything of the like?

No, we haven't actually looked. I mean, we did measure their lactate. I don't think their lactate is that much different between the two groups, but we definitely see an increase in lactate during the anaerobic exercise, which we already expect as to directly into the brain, we didn't measure that. But it is an interesting point because I published a paper last year, a review paper on traumatic brain injury and exploring the roles of both ketones and lactate in helping both the recovery and the mitigation of damage of traumatic brain injury.

Were you giving people lactate and ketones?

It was a review paper. So basically looking at all the literature so far as to what we know, what happens in metabolism when you have a traumatic brain injury and why, we came to a conclusion that ketones and lactate may be able to help with that.

Ketones are something that come to mind for TBI and concussion because if you look at, for example, Dale Bredesen's book the End of Alzheimer's, there's a whole multimodal approach to Alzheimer's or other dementia like conditions that include high amounts of dha, hyperbaric oxygen, adequate hydration, the use of intranasal light or intracranial red light therapy for the brain, and I believe either coconut oil or MCT oil or possibly ketones, I don't recall, were one of the strategies used for TBIs for concussions. And I've also seen some indications for other neurodegenerative conditions. What's going on with ketones in the brain?

So we are actually going to launch a pilot study on TBI together with the Naval Health Research center to look at specifically Ketone iq, the effect of Ketone IQ in recovery of TBI patients. And there's a university, University of Western Australia in Perth. I spoke to the clinician as well a few days ago and they are going to start a study on TBI using Ketone IQ as well. So stay tuned on that. But as far as what we know so far on tbi, what happens when, when tbi, when you have a concussion, when you have a traumatic brain injury, within the first 48 hours, what they have seen is the hyper metabolism of glucose, your brain start taking in all the glucose.

Right.

And some people say because you need an increased energy because you know the damage going on. But there are some scientists who shown, who has shown that the glucose is being pushed towards the pentose phosphate pathway to create more nadph, which could be helpful with the mitigation of the damage.

Yeah, and then NADPH being able to have a protective effect.

Correct. Mitochondria neuroprotective effect as well. So and then weeks to months after, in fact seven days after, they saw a decrease in glucose metabolism because you can only ram something up so far up before it goes back down. Because that's what the body does. You know, we always stay in homeostasis and really, you know, modulate the metabolism. So when glucose goes back down seven days, they saw a huge increase in lactate, up to like 60 plus percent metabolism being relying on lactate, showing that there is still an increase in energy. But somehow the brain capacity to upregulate glucose metabolism is, is now not able to be maintained. And then right after that, like, you know, if you look at TBI patients, you know, years after, they also experience somehow a hypo metabolism of glucose, meaning that they're not as efficient in metabolizing glucose. And this is very similar to neurodegenerative diseases like Alzheimer's. Why they call it type 3 diabetes is because there's some form of insulin resistance where the brain is not being able to uptake and utilize glucose as efficiently as a normal human being. So that's where ketone ketones come in. Right. First and foremost, ketones are brains super fuel, like it's a brain's preferred fuel. So when it's present, the brain will take it up. So because ketones are being shuttled in via mct, which is monocarboxylase transporter, it's different to glucose transporters which are glutes. Right. So it's coming in from different shuttles, different channels, so it can bypass that whatever insulin resistance you have. Secondly, we're looking at the anti inflammatory properties of ketones as well. The direct effect on of ketones on LRP3 inflammasome could also potentially help with both mitigation of the damage as well as recovery down the road. So first of all is the energy deficiency gap that may be compensated with ketones and lactate and then to the anti inflammatory properties of ketones.

Why does some people still say that glucose is the preferential fuel for the brain?

I mean under normal circumstances the glucose does use a lot, I mean, sorry, the brain does use a lot of glucose, right? But then how many people, like how many studies are there that shows that you have high glucose and high ketones and then the brain preferred ketones. Like what we know is that ketones and brains and whatnot, when ketones, when ketones are present, the brain and the heart will always take up ketones. And what's more interesting is that I know for a hot for, for sure in the heart is that when the heart takes up ketones, it's proportional to the availability of ketones in the blood. However, this is independent of the uptake of other substrates. Meaning that when they measure the vena, the arterial blood and the venous blood, so blood going in, blood going out, the uptake of glucose and fats remain the same and ketones go up. And this is especially important for a Failing heart because you are essentially providing more energy because it's uptaking more substrates and providing more energy to the failing heart. And we know in heart failure the heart actually upregulates ketone metabolism.

I didn't realize how applicable this was to heart disease. This, this is fascinating. Back to the brain. My sons just took their first dose ever of ketones. They're upstairs in our bedroom, I think right now, in close proximity listening to us. And I'm curious, when it comes to things like school performance, cognitive performance, youth intake of ketones, a, are they safe for kids, if you can say that, and B, have you guys looked at academic performance or anything like that? Or is that on the radar? Has that been studied?

So it hasn't been studied. So first of all, let me answer for kids. We have had kids. Take it. In fact, recently a gentleman called James, he, his son had almost drowned when he was a baby. Now he's six, he's having, you know, brain injury and he had to be tubed and everything. And I sent him some ketone IQ and reportedly he noticed some changes, like his son became more alert. I mean, ketone IQ is FDA grass, which is generally recognized as safe. So we have a safe profile, like safety profile and tolerability that is safe for everyone essentially. And let's put it this way, right, Ketones are. Ketones are ketones. Babies spend most of their time in ketosis.

And breast milk has a lot of ketones in it as well, doesn't it?

Just fats and you just, you are on low carbs. So most of the time babies are on ketones.

Yeah.

So having this, you know, exogenous ketones, it's essentially normal for kids.

Although people thought about that, like how much more metabolically efficient humans would be if we shifted babies from breast milk into rather than Cheerios and sugar infused Gerber to, you know, sardines and avocados and fatty fish and the like, like you know it. Fortunately, even though as you've noted, and I'm sure noticed, we have cinnamon rolls and sourdough bread and all sorts of carbohydrates around the house. But my sons have certainly grown up on a diet that's also rich in avocados and fatty fish and absent of a large amount of candy around the house, et cetera. So I suspect, even though I haven't measured their RER and compared it to that of the average child, I would imagine their RER might be a little bit more stable in terms of metabolic efficiency. And they currently use, I've had them do genetic testing and they have low glutathione production pathway so they supplement with glutathione in the mornings.

Based on some research and antioxidant.

Yeah. By some research I've recently seen on dha, particularly in adolescents, for assisting with neuroplasticity and brain support. They're now taking a decent dose of fish oil in the mornings. They are taking liver to support their methylation pathways. They're both heterozygous for methylation pathways, so they take a little bit of liver. I'm thinking about tossing some ketones in their little supplements cabinet in the refrigerator to take that as well and just see if they see an even bigger improvement.

So as far as exams and studies go, we haven't had any studies or clinical trials that looked at that. But I can tell you for sure. One of my closest friend, he uses it every time before he goes into a quiz or a midterm and he claims that it does help him focus and concentrate. Same thing with another friend in Netherlands. He, his girlfriend had ADHD and had problems studying for her university courses. So when she took ketone I.Q. she's like, wow, I can actually study focus for longer than few hours at one time now because she has always had trouble focusing.

Yeah.

So I think that says a lot. So the way I describe to people what ketone IQ does is that any activity that uses brain power, be it just cognitive work, studies, podcasts to performance. Because even if you're working your skeletal muscles, you're still using your brain a lot.

Right.

This will provide the feel that you need in order to maximize or optimize that sort of performance.

Yeah. Subjectively and based on anecdotal reports from many of my friends, combining ketones with nootropics with smart drugs such as like the modafinil or combining them with microdoses of plant medicines seem to enhance the effect of any of these brain supporting compounds that you might take. So I think there is something there related to that and this idea of stacking. Like you and I both tried some aminos today with the ketones based on that early experience I'd had with using aminos and ketones as endurance fuel. Do you personally or anything you found with people you've worked at HVMN found certain things to stack really well with ketones to enhance the effects or to play really well with ketones.

So what I personally use, I usually use ketones. Ketones like ketone IQ and green tea for pre workout because I don't drink coffee like anything that has too high of caffeine level, I'll get headaches.

So it's not the acidity, it's the caffeine.

It's the caffeine. Yeah. And because coffee always gives me headache like green tea doesn't and but if I have more than two cups of green tea per day then I'll have the same sort of headache. So I would use green tea and cat and ketones IQ for pre workout and then after workout I would use, I would have my general like protein shake which has carbs and protein and then I have ketone iq.

Yeah.

Not mixed together though. I have a shot. And then I'll have my protein shake.

Yeah, it wouldn't be that great mixed in but that's actually the first I've heard about the anabolic mtor stimulating effect of ketones with carbs and protein post workout.

Yeah.

And I'm trying to put on a little weight myself right now. So I'm going to have to start trying that.

Yeah, because that's my raw liver smoothie.

In the morning throwing in some keto.

I believe that study has been around since 2017 or 18. So they measured in vitro, specifically in those muscle biopsy, muscle biopsy cells and they saw an upregulation of Lucy mediated M2 activation. That's how they figure it out. And then couple that with the overreaching study by Haspel's group on the increase in power output after three weeks using it as post exercise recovery strategy. That confirms that.

Yeah man, it's so cool. By the way, I just tested my blood glucose again. I know we're getting towards the end of the podcast. I've stabilized, I've topped out about 78.

Okay.

So which, which again, if I were just sitting here in a normal scenario without the ketones I'd probably be at about 85, 90. And I've had a total so far today. I've probably had like 60 grams of ketones like from the get go and 40 grams, let's see two of these. So that's 20 grams plus a pretty big shot of these, another 20 grams. So yeah, I probably had 40 grams since the podcast started. Yeah. Amazing. Well, this has been absolutely fascinating and I know for people listening in, you're going to want to be interested in some of the research that LAT and I have talked about. And so I'm going to link to all that@BenGreenfieldLife.com.

Based on our partnership here with HVMN. They've given us a 20% discount code on this stuff. So if you go to BenGreenfieldLife.com ketoneiq you can use code BENG. I'll put that in the show notes as well. So you can go to BenGreenfieldLife.com ketoneiq to try it and use code BEN G. And like Lat mentioned, if you get it at Sprouts and you buy a bottle and you send it, what do they do? They scan it.

So they buy a bottle, they scan the QR code, follow the instructions.

Oh, there's a QR code on the bottle. Oh, yeah, it's right there.

Yeah. And then follow the instructions and we'll reimburse you for the first shot.

Sweet. I love it. And then all the show notes, if you guys have questions or comments or feedback for Lat and I, I do my best to review all those. You can go to BenGreenfieldLife.com HVMNPodcast for the show notes. Lat. I'm super glad you came up. You ready for some Frisbee golf? Some ketone powdered? Frisbee golf this afternoon?

More Ketone powdered?

Oh, yeah. Yeah.

And if you guys are interested in, you know, metabolic health in general, if science in general, how we break down science, for example, you know, Ben does it very well breaking down complicated science concepts into terms that people can follow but also take away for healthy lifestyles, do follow HVMM podcast as well. Cause I interview Quite.

I forgot you guys have a podcast.

Yeah, we interview Quite and this. This episode will be on HVMN podcast as well, so.

Oh, sweet. Awesome. All right, thanks a lot.

Thank you very much.