Do Ketones Actually Cause Fat-Burning, How To Use DRINKABLE Ketones, The Difference Between A Keto Diet & Ketones (& Much More!) With Dr. Latt Mansor

My name is Ben Greenfield, and on this episode of the Boundless Life Podcast, there is one study that shows just with one dose of ketones and a week of ketogenic diet— so two different groups, they both exhibit similar effect in the functional MRI where the brain regions talk to each other more often. So the brain network stability increases with ketones. So we know the brain is more active and more efficient when ketones are present. In infants, they use ketones as precursors to build brain cells, neurons. Because if you think about it, brain has a lot of fats, right? So where does the fat come from if the fat doesn't go through the blood-brain barrier? It's the ketones that is being used as precursors to rebuild the fat molecules, the fatty acids, and build those cells.

Welcome to the Boundless Life with me, your host, Ben Greenfield.

I'm a personal trainer, exercise physiologist, and nutritionist, and I'm passionate about about helping you discover unparalleled levels of health, fitness, longevity, and beyond. Ben Greenfield: My guest on today's show joined me last year for a comprehensive talk at my dining room table. He's back. The question is though, what— last time, we crushed ourselves in the gym with this whole fasted routine pre- podcasts. Did you kind of celebrate the reunion here with another—

Yes, yes, I did. I did think about you. I thought about you even yesterday because I knew we were going to have a recording. So, I actually fasted for more than 24 hours now and I woke up and I did a half an hour cardio session before we even started here. And then, now I'm going to have my first Ketone IQ of the day. Just for the podcast.

Ben Greenfield: Okay. Well, I mean, I fasted about 14 hours. There was a workout in there this morning preceded by a little Ketone IQ, but I just punished a 600-calorie smoothie. So, you win if we're matching ourselves up for our fasting capabilities. For those of you who don't know who Latt is, I always butcher your last name, Latt. Do you say Mansour or Mansour? Mansour. Mansour. It's almost like Mansour. Dr. Lat Mansour, I first interviewed him in the podcast, "Everything You Need to Know About Ketones and Ketosis," which you can find in the shownotes if you go to BenGreenfieldLife.com/DrLat. And, it's spelled with a couple of Ts, Dr. Lat. Yes. So, if you want to understand the background of what ketosis is and what ketones are, Even though we'll give you a little bit of an overview today, I highly recommend you pair this podcast episode where we kind of geek out on some of the more subtle nuances with that last episode. Latt has an MA in biotechnology from Columbia University, BS from the University of Nottingham. He's the research lead at HealthVia Modern Nutrition. They produce Ketone IQ. And, I like Latt because as you just heard, he not only talks the talk but he walks the walk, so he kind of understands how this stuff feels. I think during our last episode, didn't we challenge ourselves to see how many ketones we could actually drink flat?

We did. We drank for at least 4 or 5 shots during the entire interview, I think.

Yeah, we made it through almost a full bottle of ketone, like the big one. Yes. Yeah, which is interesting because a lot of people say because the ketone in that is 1,3-butanediol that we should have felt drunk. Yeah. I didn't. I've I felt fine.

I don't know what you—

Exactly.

And I felt fine. And if it was supposed to make you drunk, then we wouldn't have that many Olympians and world record breakers, athletes who are on Ketone IQ trying to break world records with them. So, with anything, you can always overdose something. Even glucose, you can overdose and you start puking, right? So, it's a matter of getting the optimal dose in and the use case.

If I'm going to overdose on glucose, I want to do it on Cinnabon.

I'm just saying.

You got to go down in a blaze of glory. I actually want to get to how pro athletes are using this stuff, but before we do, I think that a lot of people might be confused or need some clarity about what drinking ketones, kind of like what you do with Ketone IQ, versus just eating a ketogenic diet could do for you. And particularly, what I'm interested in is are there metabolic effects of fasting, carb restriction, a ketogenic diet, et cetera, that give you something that ketones can't?

Yes. Okay. Let's go back to Ketone 101 like what we did before, just covering the difference between an external source of ketones versus your endogenous ketones, which is your internal source that you produce yourself. So, you need to be very low on carb storage, whether it's glucose or glycogen. Either you are fasting or you go on a keto diet. That way, your body starts breaking down the fat into ketones. The reason being your brain needs energy source and usually it burns on glucose. But when you're very low on glucose, you will need ketones because fatty acids can't pass the blood-brain barrier. Therefore, it needs to be broken down into smaller molecules, i.e., ketones.

I'm going to interrupt you right there because I think that's something a lot of people don't realize. You can burn fats as a fuel. Your muscles can burn fat as a fuel, especially if you're carb-restricted because that is an alternative fuel source. Those fatty acids can't cross the blood-brain barrier, therefore they need to be converted into ketones before they can.

Thank you. Yes, that's the whole point.

Yep.

And then, the external source of ketones like Ketone IQ is essentially bypassing that physiological state where you need to be low on glucose. So, you are not restricted by the diet or by by a fasting condition in order to have access to ketones. So, you directly insert ketones, essentially the molecule, into your body to get access to it.

Ben Greenfield: Are there any other organs besides the brain that would have difficulty utilizing fatty acids due to barrier mechanisms or anything else that would also prefer ketones in that state?

Bjoern Borges: Not that I know of in terms of difficulty in terms of barrier. However, when I was in Aarhus University in Denmark end of last year for a symposium for Cardiovascular Disease by the Danish Cardiovascular Society, they actually created a tracker to put into PET scan so that they can track where ketones go when they inject them into the finger and then they track every 5 seconds and see where the ketones accumulate. And surprisingly enough, while we do know that ketones do go to the brain, majority of the ketones are being soaked up into the heart. So, we know that the heart actually prefers ketones whenever it's available. And they publish a paper shortly after that on Christmas Eve by giving heart failure patients Ketone IQ. And, just one dose improved cardiac output, stroke volume, and ejection fraction.

So, let's say you or a loved one were at risk, God forbid, of a heart attack, it might be a good idea to have ketones around so that if an incident occurred, you could ensure that the heart is getting some kind of a fuel as it goes through that hypoxic stressful event.

Exactly, hypoxic stressful event. A lot of heart complications, it's because of the deficiency in energy, deficiency in either glucose or deficiency in some form of blockage in the arteries causing deficiency in blood flow and all of that. So, giving them ketones may actually provide them with the efficient energy and fuel that they need. And it's funny you mentioned loved one. I'm so passionate in this area, it's because my late father died of stroke and before that, he had a heart attack. So, I wish I knew about ketones then like 20 years ago and so that he can actually prevent those events from happening.

Yeah, I wish I'd known about ketones years ago for a different reason because when I was in triathlon and adopted a ketogenic diet, I was using MCT oil during the race. And, as you can imagine, racing an Ironman after 8 hours of drinking MCT oil, there's some disastrous occurrences in the lower GI tract. So, yes, it would have been handy back when I was racing. Now, I interrupted you as you were going to the differences between a ketogenic diet and drinking yourself into ketosis. Right.

So, if you are on your own ketosis, your own ketogenic diet, ketogenic production, you obviously are going to have a more consistent ketosis versus if you take it externally, it will last you probably 6 to 8 hours if you're not working out. And if you're working out, it will last a little bit shorter. So, that means you either have to top it up or you just have to use it for certain use cases. If you are aiming for a prolonged sustained ketosis, then you obviously have to top up. So, there goes your question earlier, is there any conditions or any benefits that the ketogenic diet or the endogenous ketones can have that Ketone IQ cannot provide? So, in that sense, I think the metabolic shift that you get from a whole diet overhaul or a lifestyle overhaul that can, for example, reverse insulin resistance. That may not happen with just external ketones. You actually have to decrease the glucose. You actually have to give your body enough time for it to repair the insulin secretion pathways in order to increase insulin sensitivity and reverse the resistance.

Right. So, when I'm consuming exogenous ketones, I am getting a readily available fuel for, say, something like performance enhancement, appetite suppression, something that the heart could effectively use. The brain could effectively use, et cetera. However, if I am doing that and also say eating a high amount of calories more than I'm burning or consuming excesses of glucose and carbohydrate, I'm not going to get any advantages from the weight loss, insulin management, blood glucose control standpoint. And, I think that's something that you and I probably think is glaringly obvious, but I think a lot of people don't realize. Drinking ketones is not the same as being on a ketogenic diet if you're looking for the metabolic benefits from a weight loss or blood glucose standpoint.

Yeah, it's the same as taking Ozempic, right? Ozempic severely restrict your appetite and therefore you are eating less and then you lose weight, right? So, it's not that Ketone IQ is going to be your magic pill that answers to all your problems, But, it does help tremendously, especially even if people who are going on a ketogenic diet for weight loss journey, they do use Ketone IQ to sort of, one, put them in a deeper ketosis state and then two, to enhance or augment the appetite suppression aspect of things. Especially when they're on calorie deficit, a lot of them, they will experience fatigue. And, as you and I know, we do a lot of podcasts, we do we speak in public. Those instances, these people may need the extra boost for the cognitive alertness as well as the coherence as they deliver their speech.

Ben Greenfield: Yeah, that's a good point. And alcohol itself, if I remember, is 7 calories per gram. So, if you were consuming exogenous ketones, obviously they're so potent, you're not consuming a lot of calories of them. But, is a bottle of Ketone IQ same thing, about 7 calories per gram?

Yeah, it is 70 calories per 10 grams. Yeah. So, 7 per gram.

Okay. So, you'd account for that if you were using ketones for weight loss for your daily calorie intake, but it's not that many calories, 70 calories of ketones.

Or, if you want to, you can just fast and just have Ketone IQ. And, that makes— like Ketone IQ, I was just texting my ex-colleague yesterday and he's going through a 72-hour fast, which I couldn't do. But, he said like Keton IQ made it a breeze.

Yeah. Now, when it comes to the type of ketones you're going to make when you're on a ketogenic diet or restricting carbohydrates versus drinking an exogenous ketone, is there a difference either from a mechanism of action standpoint or a chemical standpoint between an endogenous and an exogenous consumable ketone?

Great question. Now, the main form of ketones that our body use for energy and being transported throughout our body is beta-hydroxybutyrate, is BHB. And, the ketone that you make in your body would primarily be BHB and then it will reversibly be converted either into acetone or acetoacetate. So, let's not talk about those two, let's talk about BHB primarily because we use that for energy and that is being measured when you measure your blood ketone levels, that is the ketone that you measure. The BHB being produced in your body and the BHB that gets converted from Ketone IQ in your liver is exactly the same as molecular-wise. BHB is BHB is BHB and your body will recognize it the same and will utilize it in the same exact way.

1,3-butanedial from Ketone IQ would go through liver first, get converted into BHB. That BHB would then be identical in configuration to the BHB produced by your body when you're in a carb-restricted state.

That is correct. So, one way to really reaffirm that is to measure your blood ketone levels because as I said, if you measure blood ketone you are measuring blood BHB. So, if you're on a ketogenic diet, you measure your blood ketones, you know what level they are, you drink Ketone IQ and then you measure your blood ketones, it is also measuring blood BHB and you will see that it gets converted.

Ben Greenfield: Got it. And, I'm not maliciously trying to make you shoot yourself in the foot here, but why wouldn't you just use BHB?

Bjoern Borg: Great question as well because BHB is in the form of free acid. It's either because it's literally acid. So, as part of our $6 million contract with the military, we did one of the tasks to— we did compare ketone ester and free BHB acid. And, what happened was the people who tried it, they almost killed themselves because the severe heartburn and the severe GI irritation was too much.

I have some bottles of pure concentrated BHB in my refrigerator that I occasionally use and the taste goes away after about 3 hours. It's pretty intense.

It's very extreme because it's just acid. And that's why people create ketone salts because you're binding the acid with sodium, magnesium, potassium. But then, when you combine it with salt, you're overloading with salt. And then, on top of that, when you overload it, you also have GI issues. So, that's the whole reason why we chose R-1,3-butandiol. But it's a great question because why don't you directly take the molecule itself? But the reason is because it's too acidic for your GI.

Yeah. Yeah, I won't lie, the BHB, I mean, just in my own testing, it keeps your ketone levels elevated for a longer period of time, but you have to get past the heartburn, the indigestion, the taste, et cetera. I'm sure there are ways around that, but it's difficult to use BHB just from a pure taste and logistical standpoint. And then, you mentioned something really important because a lot of people can get ketone powders which are in the— they're bound to a salt. But, to actually have enough ketones in that to reach ketosis, you have to consume so many salts that you get gastric distress. You're drawing a lot of water into the intestines.

Exactly. And, with everything else in metabolism, we are always striving for the optimal level and not just getting higher and higher and higher just because something is good.

Okay, got it. I'm glad you worked out this morning because I got a lot of annoying questions for you. So, some people say ketones are the preferred energy for the brain. You've already established they can cross the blood-brain barrier, so they are an energy for the brain. But, this idea of the preferred energy for the brain, are there studies on that that showed the brain with the presence of glucose versus the presence of ketones will preferentially turn to the ketones as a fuel source?

I believe so, but there is one study by Mujica Parodi that shows the increase just with one dose of ketones and a week of ketogenic diet. So, two different groups. They both they both exhibit similar effect in the functional MRI where the brain regions talk to each other more often. So, the brain network stability increases with ketones. So, we know the brain is more active and more efficient when ketones are present. Now, another point is this is an interview I did with Dr. Tommy Wood from Seattle. And he actually pointed out that in infants, they use ketones as precursors to build brain cells, neurons. Because if you think about it, brain has a lot of fats, right? So, where does the fat come from if the fat doesn't go through the blood-brain barrier? It's the ketones that is being used as precursors to rebuild the fat molecules, the fatty acids, and build those cells. So, that's a very interesting point that I learned not too long ago.

Is it true that breast milk is rich in medium-chain triglycerides and that would be a way it could support that?

I'm not entirely sure, but I mean breast milk is high in fat and low in sugar. So, that is essentially a ketogenic diet for the infants.

Ben Greenfield: Yeah. I don't remember. I'm not Joe Rogan, so I don't have a Jamie to look it up for me right now. But, I'm pretty sure, don't quote me on this, we may need to double-check that breast milk is rich in medium-chain triglycerides. Thus, let's say that I'm right and it were, then you're essentially getting triglycerides that can readily be converted into ketones cross the blood-brain barrier in an infant and be used for neurogenesis. Yeah. Interesting. Do you think there's a way that the brain switches somehow between these two fuel sources throughout the day, glucose and ketones, or has a way of knowing which to burn?

Oh, yeah, absolutely. I think every organ— this is what a lot of people misunderstand with metabolism. Just because you switch one off, and we know that if you switch Glucose on, if you upregulate glucose metabolism, fatty acid oxidation goes down. That we know, it's called the Randle cycle and vice versa. However, both of them actually happen at the same time. It's just the rates are being upregulated and downregulated. So, it is very possible that every part of our bodies are metabolizing different fuels at the same time, it's just at different rates.

So, you alluded to the way that the brain works when it's on ketones. Obviously, the name of your product is Ketone IQ. What kind of studies have been done on things like I drink a bottle of this before I take a test or before I'm preparing show notes for a podcast or going through very intellectually stimulating material, anything like that? Have you come across studies that show a direct impact of ketones on cognition?

Bjoern: Yes, we have seen. So far, the studies have been on ketone esters, so that's it for transparency. Say ketonases have shown increase in cognition in athletes and also in our $6 million contract that I mentioned earlier in the military. In hypoxia, we also saw the increase in memory recall and increase in cognition and vigilance. Now, for Ketone IQ per se, we do have a grant currently sitting pending Congress approval for budget with the Naval Health Research Center looking at TBI, so traumatic brain injury. So, that will be very interesting to look at the effect of Ketone IQ on injured brains and coordination and all of that. And, we are also submitting a couple of SBIRs with the University of Alabama on cognition, especially on a specific protocol where we mentally fatigue somebody and then we make them take Ketone IQ and then give them more cognitive tests.

Ben Greenfield: I mentioned earlier that I wanted to ask you about how professional sports teams are using ketones. You even see, if you watch the Tour de France, they're handing them things to drink before and after. Do you have any inside knowledge of how they're actually using these, before, during, after, how much, anything like that?

Sure. I mean, we have been partnering with Visma-Lease-a-Bike. I mean, they just sort of won Tour de France last year— no, the year before. And, they ranked quite high last year. And, they have been using it primarily for recovery actually. We have athletes who use it as a pre-workout. So, they'll take it half an hour before the workout and then top it up every 2 hours. But for Vismav, our partner, they have been using it for recovery primarily. So, after workout and before bed because the data is showing the compounding effect of using Ketone IQ as a recovery fuel. It's very, very powerful. Now, albeit even using it for acute usage for pre-workout has been powerful as well, but for them, they just prefer to use it after.

You said recovery and sleep. I want to tackle those. So, recovery, is it because it's having some kind of an effect on glycogen replenishment or glycogen sparing? Is it an anti-inflammatory effect? What's going on from the recovery standpoint?

You mentioned everything basically. So, we do have glycogen sparing effect. Glycogen sparing effect is basically your glycogen stores is essentially your glucose stores as you're exercising. So, we keep about 2,000 calories worth of glycogen in our body on a standard basis. And as you exercise, you will start to deplete these glycogens. And what ketone does is that it will spare your glycogen and make sure that you can last longer. So, this is very important for endurance exercise where you want to last long and go further. So, glycogen-sparing effect. And then, on top of that, we have also seen when people take ketones, After exercise, they increase glycogen resynthesis, increase mTOR activation for protein synthesis. And recently, we are just wrapping up a study from KU Leuven with Geert Poffet, one of the bigger names in the ketone research world. And he basically conducted a study with Ketone IQ looking at recovery, angiogenesis, and EPO.

By the way, some people might not know what that is, so you might want to explain those terms.

So, EPO is erythropoietin, which is a signal that gets sent to your bone marrow to create more red blood cells. So, more red blood cells means more oxygen delivery and better recovery. And angiogenesis means new blood vessel formation. So, what we have seen is that with Ketone IQ, when these athletes or these participants are using it for recovery, we are seeing improved blood delivery, improved oxygen delivery and new blood vessels formation. There are biomarkers that show that, and that may also contribute to why these people are recovering faster and thus compound the effect of the recovery and having a higher adaptation to the increased load of exercise.

Ben Greenfield: Wow. And, that list of effects that you mentioned, you talked about increased mTOR activation leading to increased muscle protein synthesis, which we call in exercise science sometimes MPS. Typically, when you see increased MPS, it's related to either sometimes hormones, testosterone, growth hormone, et cetera, most often amino acids, some sort of complete protein source or something like that that increases MPS. I hadn't seen before this information about ketones actually increasing MPS. And, it's interesting for two reasons. One, I wasn't aware it would have an impact like that on recovery. And two, it makes me think about whether there would be enhanced muscle protein synthesis if you were to include ketones with either a protein smoothie or a serving of protein or amino acids or something like that. Have you thought about that?

Yeah, that would be the next step, the expansion of that research for sure. Because in that research particularly, they looked at using ketone ester together with protein and glucose and they saw the mTOR activation. So, the next step The next natural step, as you said, would be looking at whether or not muscle synthesis increase, especially after resistance training. If you look at Dom D'Agostino's work as well, they have looked at using acetoacetate diester, another form of ketone ester, in preventing muscle loss in cachexia in cancer patients. So, that has also been shown to mitigate muscle loss. So, not only you can sort of keep the muscle, you could potentially increase muscle growth if you use it correctly.

Alright. So, the sleep part, what about the sleep part?

So, the sleep part, one study just recently, I think last year, they looked at the decreased REM sleep due to vigorous exercise and then they gave them ketones and that REM sleep got normalized. And, they also looked at adrenaline, noradrenaline that was increased, so increased stress after vigorous exercise and then decrease dopamine when they are asleep. So, when they give them ketones, again, those get normalized to a healthy person's level.

Ben Greenfield: That's interesting. And, a lot of these sleep studies on exercise's impact on sleep parameters, you'll see the sleep or the exercise done in the early evening or 3 hours or so prior to bedtime. Do you know what time people were doing this vigorous exercise?

I can't recall exactly what time.

Ben Greenfield: I'll tell you why I ask. A lot of times when I travel, even though I like to work out in the morning, I'm relegated to working out in the evening due to the travel schedule. What you're implying here, I think, is that theoretically, if I didn't want an evening exercise session to deleteriously impact sleep parameters, something like using ketones, I'm assuming after that session, not only for the recovery and muscle protein synthesis but to stave off the impact on REM sleep and dopamine signaling could be something to experiment with.

That is correct. And on top of that, we have currently an NIH grant in collaboration with Johns Hopkins that is under review looking at sleep apnea. So, looking at using Ketone IQ to mitigate or prevent sleep apnea. Or improve the symptoms of sleep apnea in some patients.

Huh, interesting. I wonder why that would be. Would it be because there's a lower oxygen need in the presence of ketones?

I think rather than thinking of lower oxygen need, it's more of an increased oxygen delivery. So, as I said earlier, right, the EPL, blood vessels formation, angiogenesis, and we're talking also improved symptoms in heart failure patients. Again, that is like blockage and reduced blood delivery and reduce substrate delivery to the heart. Same thing here, right? If you are having sleep apnea, obstructive sleep apnea, you're essentially decreasing oxygen being delivered to your body. And over time, you are increasing your risk of mortality, cardiovascular disease, and obesity. But with ketones present, we have seen the previous paper which used ketogenic diet, they saw an improved carbon dioxide sensitivity as well as improved oxygen saturation. And they do think that it is the ketone that is doing the work. And therefore, we are embarking on this journey to apply for a bigger grant to look at using KetoneIQ to emulate the same effect.

Ben Greenfield: Wow, amazing. Okay. So, some other hopefully not too silly or dumb questions for you here. Is there a difference between if I have the ketones with food versus without as far as how quickly I'm going to get into ketosis, the absorption, anything like that?

Great question. Ketone esters previously have shown that with food, the effect of increased ketones gets lowered. But, with Ketone IQ, we have tested it again and again, there is no effect on whether you're taking it with food or not. I assume that is because 100% of the beta-hydroxybutyrate is getting converted in the liver, whereas ketone ester, part of it is the BHB that gets released directly into the blood. So, it gets affected by whatever food that you are eating.

You mean that the food would somehow like slow the absorption rate of a BHB?

Yeah, it could be, or whatever hormones that's going around. As to why exactly that is, no one knows, no one really looked into it. But we have seen that people who take it with food, ketone ester does not increase the blood ketone levels as high as they would if they're fasted.

Okay. I have a little bit of a biochemical conundrum I want to throw at you.

Sure.

I sometimes, if I have a workout session in the morning, usually fasted, and then breakfast, and I look at my blood glucose monitor, I get a hypoglycemic response to breakfast. Often within 40 minutes of eating, my blood glucose will drop down into the 50s. Kind of an issue obviously because I'm often going off to record a podcast or whatever after breakfast. If I have ketones before my morning workout, the same hypoglycemic event occurs but has no impact on my cognition, my function, dizziness, brain fog, all the things that would occur if I were at a blood glucose of 50 to 60 in the absence of ketones. Explain to me what's going on here.

What kind of breakfast do you have?

I have a smoothie. It doesn't have a lot of carbohydrates in it, sometimes a little bit of blueberry.

Okay. So, it's not like a breakfast devoid of carbohydrate, right?

I would say it varies, but whether I put some blueberries or banana in the smoothie or whether I have no carbohydrates in the smoothie, there's almost always a hypoglycemic event postprandial within about 20 minutes after my smoothie that is non-problematic with ketones but very problematic without ketones.

I can't really comment on the one without ketones because I think it has something to do with your personal metabolism, how you react to foods and how your insulin works. So, I think in order to find out more, you need to find out what is your insulin doing during that time, looking at your glucose tolerance test and looking at— because some people, myself included, when I did a glucose tolerance test, my I also have a reactive, they call it reactive hypoglycemia. So, it doesn't go up, but then when it goes up, it drops very quickly.

That's the term I've heard others describe this as, reactive hypoglycemia.

Yeah, that's what I have as well. So, it's something to do with basically making your body accustomed to glucose, but because you and I probably always have on the lower carb side and because of that, our bodies sort of react to it. In an exaggerated way.

Oh, okay. So, basically, if you do have carbohydrates, then you would be very reactive as far as the insulin response to those carbohydrates and thus risk some pretty intense hypoglycemia if you're a low-carb person who goes out for pizza, say.

Exactly, exactly.

And then, if you're in that low-carb state, hence the ketones, right?

Hence the ketones. So, ketones also lower glucose postprandial, but that is a complete different mechanism of action. What the researchers think is the mechanism of action is actually the decrease in gluconeogenesis in your liver. So, that's a process of your liver creating glucose. So, as you all may not know that even if you're not having sugar or not having food, your blood glucose level will always be baseline because of how important glucose is as a substrate, as a fuel. So, that's because your body is constantly making up glucose from other sources like proteins and whatnot.

Gluconeogenesis, as the name implies, and the liver is engaged in that frequently.

Yeah. So, what we're thinking is that when ketones are present, it is sending a signal to your liver to downregulate gluconeogenesis because it is perceiving that your body is having sufficient fuel so you don't need to make more glucose. But because of that, but because of the presence of ketones is also giving your body the fuel it needs and it's going into your brain and really stimulating the brain activity and as well as supplying the brain with energy, you are not feeling that mental fatigue state versus if you're just having a reactive hypoglycemia without ketones.

Yeah. So, back to a preferred energy source for the brain, especially in a state of carbohydrate or glucose depletion. It makes sense. And by the way, I didn't know that about ketones potentially lowering gluconeogenesis via signaling mechanism.

Yeah. Look at Dr. Jonathan Little's work. From University of British Columbia. He published quite a few papers on healthy individuals, obese individuals, and diabetic individuals using ketones postprandial, and they all saw a drop in blood glucose. And, that's what he postulated.

Ben Greenfield: Okay. And, in terms of how long someone could have elevated ketones after drinking, let's say, a standard serving, say, a bottle of Ketone IQ, the small white bottle, not the big multi-portion bottle, About how long or does that vary from person to person can one expect to kind of have that mental edge or have the elevated ketones?

Generally, it is quite reliable in terms of consistency. And, if you are sedentary, you're not working out, you're using it for work productivity and cognitive alertness, it will last up to 6 hours. And, if you're working out, it may last for maybe 2 to 4 hours. So, Obviously, as you're working out, if you're using it as a pre-workout, you are going to be burning the ketones off. And this is being done or being observed as we do all these studies and these people are getting pricked and looking at their blood ketone levels after each hour versus whether they're exercising or they are sedentary.

Now, you say I'm burning the ketones off, but let's say a bottle contains 70 calories. I don't know about you, but I burn a lot more than 70 calories during the workout if I'm not being lazy. Surely, the body is burning other fuels in addition to the ketones, but are the ketones, especially if you're working out in a fasted state, allowing you to tap into fats more efficiently, doing something else beyond just the calories and the ketones that you're getting in the bottle itself?

That's a great point because 70 calories, people like you, for example, you'll burn it in 15 minutes. So, it's like what then are you tapping into? And the answer is correct, you are tapping into your fat, especially if you're doing fasted, your glycogen stores are going to be depleted. So, the only stores that are available to you would be your fat storage. But one good thing that happens when you drink ketones is that you are also upregulating your ketone-related or ketone-associated metabolic enzymes. So, that is what has been measured, all the enzymes that is converting beta-hydroxybutyrate into acetyl-CoA, and that goes into the Krebs cycle and creates ATP, which is the energy source for the cells. That gets upregulated. So, even though it's only 70 calories, so in terms of fuel, it's not a lot, but it is sending signals to upregulate keto metabolism. So, when you are burning your own fat and you're already low on sugar, obviously, some of the fat will also get converted into ketones. And, that makes keto metabolism more efficient.

Ben Greenfield: I think without knowing it, you may have answered my next question which I wanted to ask, which was based upon the concept that a lot of people think that when you have ketones, it would shift the body out of fatty acid oxidation because the body has to choose to burn these ketones first before it'll burn anything else. People say the same thing about alcohol, right? If you have a big meal with alcohol, you're going to gain weight more quickly because your body needs to burn the alcohol first. It sounds like maybe the body could be burning the ketones preferentially as the first fuel that it goes to, but then there is a switch that allows for upregulated burning of the body's endogenously produced ketones?

That is correct. That's exactly what I would answer.

Huh. That is so cool. So basically, It's almost as though I'm jumpstarting my body's own fat-burning process by having a shot of ketones and then exercising.

Yeah, absolutely. And don't forget, if you're using it for fat burning and weight loss, you're also adding that appetite suppression effect as well.

Yeah. Is that GLP-1-based, that appetite suppression effect?

It's very interesting. A lot of doctors actually believe that it has a GLP-1-like effect. Of ketones in terms of the drug-like property. But so far, we haven't got any studies that specifically looked at that, but it'll be a very interesting study.

Ben Greenfield: Now, for athletes, back to people like these Tour de France riders, I'm kind of guessing they're doing more than ketones. There's this term now that I see thrown around in, say, exercise science called the dual fuel. Type of approach where you simultaneously elevate glucose via, let's say, a sports drink or an energy bar or a goo or a gel or something and ketones at the same time to kind of tap into the best of both worlds, so to speak. What do you think of that type of approach?

I think it's good because you are providing your body the option because your body will always choose the more efficient fuel. So, same thing with how we advise our athletes who are not keto-adapted, who are not on ketogenic diet, we'll ask them to take Ketone IQ together with carbs because it's not meant to replace the carbs, especially if it's only 70 calories. You are not fueling yourself with that with just one small bottle of ketones. But what it's doing is essentially giving the signal for glycogen sparing, for increased mTOR, for all these others. Additional signaling effect that will then make your glucose and your glycogen more efficiently used.

Ben Greenfield: And so, theoretically, if I were to want to run, let's say, like a— I don't know, let's be realistic here. Let's say a 4-hour marathon. I wouldn't necessarily have to bring 4 bottles of Ketone IQ out there with me, especially if during exercise it might give me 2 to 4 hours. I could theoretically maybe have a bottle before, a bottle halfway through, use carbohydrates during the event, and still get the benefits of glycogen sparing and upregulated utilization of my own endogenous ketones with an approach like that.

That is an exact protocol that we would ask people to do. We will ask them to take half an hour before and then top it up an hour and a half into your workout, which is 2 hours since the first dose, and just top it up once. And then, if you finish the race, that's it. That's the 2 doses.

Yeah. It's well known by a lot of people, not just exercise physiologists, that if you're working out hard, you tend to burn more carbs. If you work out easy, you kind of shift into fat utilization. So, let's talk about anaerobic exercise, a CrossFit workout, whatever, a Wingate cycling power protocol, something that's a little bit more speed, power-based, strength training intense. Any advantage there to ketones? I mean, there's obviously maybe a little bit of a cognitive benefit, but is there anything metabolically that goes on? Have you looked with this in research or anything like that?

Yes. For the longest time, ketones have been known or have been assumed to be only beneficial in endurance exercise just because it comes from the fatty acid oxidation pathway, it comes from the fatty acid conversion, and therefore should be considered the fatty acid line, which is not the glucose glycolysis line or pathway, which does not require oxygen, right? So, we always think that anaerobic means we need to go into glycolysis, we need to tap into our glucose, which is still true to today. But in the recent study we published in January with University of North Georgia, for the first time in human history, we are actually looking at Ketone IQ in anaerobic exercise. And we put these participants through Wingate test. So, they have to go on a stationary bike pedal as hard as they could for 10 seconds, rest for 30 seconds, and repeat that for 5 times. So, they do that for 5 times. And what we have found is very, very interesting. We found that they have improved peak power, improved average power, improved cadence, as well as decreased fatigue index. Now, we also measure the respiratory exchange ratio, the RER, showing that they are burning more glucose.

Ben Greenfield: And, by the way, the respiratory exchange ratio just for people listening in, if that's a lower value, it tends to indicate higher amount of fat burning, higher value up to what, like, is it 0.8 where it tops off or 1.0? I'm trying to remember now.

Yeah, 1.0.

That would be like full carbohydrate utilization.

Yeah. So, all these people, all these participants are above 1, but the Ketone IQ group, they are significantly lower compared to the placebo group. So, it is pulling it towards fatty acid oxidation at the same time. However, if that's the case, if it is shifting over to fatty acid oxidation, as a physiologist and a metabolism scientist, I would assume they would perform worse than the placebo group, but they perform better.

Ben Greenfield: They're burning glucose less. So, yeah.

Bjoern Borg: Exactly, but they're performing better. So, what we think is happening here could be an analgesic effect on the brain.

Like influencing the rating of perceived exertion.

Exactly. So, they are feeling less painful because these exercises are designed to elicit painful sensation localized in the muscle area. And what we're thinking Ketone IQ is doing is essentially numb the pain so that these people can push further and push harder. And we've seen that in the power and the cadence as well as decreased fatigue index. So—

Another thing that came across my mind as you were explaining the part about— oh, I remember what it was. So, you explained how it seems to have a beneficial impact on anaerobic performance. But related to performance and I guess longevity and anti-aging, you see guys like Bryan Johnson doing 60 days in a— well, there's a hyperbaric oxygen chamber, which I've used as well. Behind me in the— I don't know if you can see it in the podcast, but there's one of those HyperMax units from 10X where you breathe 93% oxygen for 15 minutes. There's units like the Cell Gym now that kind of go back and forth between hypoxia and hyperoxia or the LiveO2 where you do that while you're exercising. With all these oxygen delivery mechanisms, I'm just curious because I think it was in the last podcast You made a pretty compelling case that ketones assist when exercising in hypoxic conditions or just living in hypoxic conditions, probably due to this effect on EPO, red blood cells, et cetera. What about hyperoxic conditions? Do you think there would be any effect of, say, having elevated blood ketone levels when I get into a hyperbaric chamber or do an exercise with oxygen training session?

It's funny you mentioned that because I just recorded a few weeks ago with Gabby Reece. At her house and she has a 2-seater hyperbaric chamber. And we were just saying the next time I go, we have to try using Ketone IQ before we go in and see what the effect is. I mean, the answer is I don't know. We haven't got any studies showing the effect of that. But also understand that the sensing of oxygen via HIF, which is the hypoxia inducible factor, is a factor that it's directly affecting your DNA and a promoter of a downstream cascade of events that affect your adaptation to hypoxia. Now, that is a very sensitive pathway. So, any change in oxygen level will trigger that. And as a result, you can see myriads of effect on the cellular level as well on an organ level. So, I don't know what will happen if you do take Ketone IQ before hyperbaric chamber or in a hyperoxia condition.

Yeah. I don't know if you guys had researched that or not. It would be interesting with as many people as are now using protocols like that whether it would be advantageous or disadvantageous potentially to have elevated ketone bodies during those sessions. I just, in the middle of the podcast, I'm not thinking of a mechanism of action that would allow it to be any more beneficial than not being in ketosis, but I'm not sure. How about this? Because I was kind of stalking you on your website a little bit. Cancer is a topic I've talked about many times before on the podcast, and I saw that you guys, I think, are opening up or starting some kind of a clinical trial on colorectal cancer.

Yes, we are partnering with University of Pennsylvania and they are already recruiting for a few months now. So, they previously used ketones and keto diet and they published in Nature as well, which is a very great big paper, high impact factor paper showing the effect of ketones in stopping colorectal cancer cells from dividing and propagating. So then, they reached out to us and they want to partner to run a bigger trial to use Ketone IQ to treat people at high risk of colorectal cancer and give them Ketone IQ as a form of prophylaxis or prevention against colorectal cancer?

Ben Greenfield: My father died of colorectal cancer. Two cousins died of it. One cousin had it and had a resection. My grandfather on my mom's side had colorectal cancer. So, this is very interesting to me. It just kind of makes me want to— as you know, I've been kind of on the ketone bandwagon for almost a decade now, but I plan on continuing that as a preventive remedy. So, I can eat as much red meat and drink as much alcohol as I want.

Yeah. But, check out the paper. I think you'll find it very interesting because— Yeah.

I have it marked. I'm going to put in the shownotes too. It's on Nature, right, that one?

Yeah, yeah, yeah. And, they even reverse it. When they put the animal models on keto diet, the tumor score goes down. But then, when they reverse it back to standard diet, the tumor actually start propagating again. And then, they do it both ways. And, it's interesting how as soon as ketones are present, they're like, it's totally suppressed.

Ben Greenfield: Yeah, kind of makes sense also based on a lot of Thomas Seyfried's writing on the metabolic theory of cancer. So yeah, that's super interesting. Are you guys planning— I mean, you introduced a caffeinated version. You got the regular version. You have the peach mango flavor, I think, the green apple, the regular. You have the big bottle. Any other innovations coming down the pipeline?

In terms of innovation, I think we are iterating on improving the flavor. I think the biggest barrier for people who do not know about ketones, like you and I, we've been doing ketones for almost a decade, right? We've been knowing the area. I think for the general population who have not heard of ketones, the taste have always been the barrier. Therefore, our innovation would be to improve the flavor and really compete in the 5-Hour Energy drink, the Celsius, the Monster sort of world where people are getting overstimulated by caffeine and getting desensitized by caffeine. And, they just need something that is a cleaner energy source that is directly providing them with the fuel but not a stimulant that will affect their sleep quality later on. And, on top of that, Also, remember that all these stimulants are only stimulating your brain power, is stimulating your heart rate and your blood pressure, but it does not provide you with the fuel you need. You are still taking it from within your body, whereas ketones are actually providing you with the fuel directly into your body. So, that's where our innovation stands and really going into the mainstream of food and beverage and the energy drinks world.

Yeah. And, by adding, I think it's about 100 milligrams to the green apple flavor. Did you see any research at all on the combinatory effect of caffeine and ketones or is the caffeine just for a little extra edge?

I think there are some studies that may show improved effect. My hypothesis is that, like I said, caffeine increases your brain energy energy demand and ketone provides that energy supply. So, that's why it's synergistic. So, in terms of how effective that is in the performance and all that, I think we need a whole study for that.

Yeah, yeah. Okay, cool. And it is the green apple flavor, it's the caffeine one, right?

Yeah, green apple. We have the peach as well. I think this week we are releasing the raspberry lemonade. It's going to— Yeah. So, I'm going to send you some.

I mean, if you really wanted to appeal to the to the keto enthusiasts at heart, you develop the old-fashioned flavor with a splash of liquid gasoline for those of us who just crave that acidic.

Yeah. I mean, I have this big bottle just sitting by my desk. I still drink this because it's easier to pour out 2 doses.

Yeah, yeah. Wow. I love those big bottles, by the way. They were pretty easy to just accidentally drink half the bottle though before half the day was over.

But, all right. Just sip on it.

Yeah. Yeah, exactly. Alright. So, all the shownotes, and I'm going to include robust research for those of you who want to dive into the research along with the previous episode I did with Dr. Latt, which was also incredible. Go to BenGreenfieldLife.com/DrLatt. That's BenGreenfieldLife.com/DrLatt for the shownotes. Latt, the only thing I'm a little bit heartbroken about is that we didn't get to do this at my kitchen table. While trying to inebriate ourselves on 1,3-butandiol.

Hey, you know, anytime, anytime you are, I'll be there right away because you know I enjoy the food that you make and it was a great company, great time. I've learned so much and all your gadgets as well. It's like I want to see what you're playing with these days.

Okay, you have my word, the 3P at my new place in Idaho. You're going to love it. You'll drool. Yeah.

Just let me know when, I'll book my flight.

Alright, folks. I'm Ben Greenfield along with Dr. Latma Sohr signing out from BenGreenfieldLife.com. Have an incredible week. And the shownotes are at BenGreenfieldLife.com/DRLATT.

To discover even more tips, tricks, hacks, and content to become the most complete boundless version of you, visit BenGreenfieldLife.com. In compliance with the FTC guidelines, please assume the following about links and posts on this site. Most of the links going to products are often affiliate links, of which I receive a small commission from sales of certain items, but the price is the same for you. And sometimes I even get to share a unique and somewhat significant discount with you. In some cases, I might also be an investor in a company I mention. I'm the founder, for example, of Kion LLC, the makers of Kion branded supplements and products, which I talk about quite a bit. Regardless of the relationship, if I post or talk about an affiliate link to a product, it is indeed something I personally use, support, and with full authenticity and transparency recommend in good conscience. I personally vet each and every product that I talk about. My first priority is providing valuable information and resources to you that help you to positively optimize your mind, body, and spirit. And I'll only ever link to products or resources, affiliate or otherwise, that fit within this purpose. So, there's your fancy legal disclaimer.