Ben Greenfield [00:00:00]: My name is Ben Greenfield and on this episode of the Boundless Life podcast.

Latt Mansor [00:00:04]: 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.

Ben Greenfield [00:00:48]: Welcome to the Boundless Life with me, your host, Ben Greenfield. I'm a personal trainer, exercise physiologist and nutritionist and I'm passion helping you discover unparalleled levels of health, fitness, longevity and beyond.

Ben Greenfield [00:01:09]: 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, Lat, you know, last time we crushed ourselves in the gym with like this whole fasted routine pre podcasts, did you kind of, you know, celebrate the reunion here with another.

Latt Mansor [00:01:32]: 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. So. And then now I'm going to have my first Ketone IQ of the day just for the podcast.

Ben Greenfield [00:01:57]: Okay. Well, I mean, like mine, I fasted about 14 hours. There was a workout in there this morning preceded by a little Ketone IQ, but I just punished like 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 LAT is, I always butcher your last name. Do you say Mansoor or Mansoor?

Latt Mansor [00:02:22]: Mansor.

Ben Greenfield [00:02:23]: Mansor. It's almost like Mansor. Dr. Latt Mansor. I first interviewed him in the podcast everything you need to know about ketones and ketosis, which you can find in the show notes if you go to BenGreenfieldLife.com/ DrLatt and it's spelled with a couple of T's., Dr. Latt.

Latt Mansor [00:02:42]: Yes.

Ben Greenfield [00:02:43]: 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. Lat has an MA in biotechnology from Columbia University, BS from the University of Nottingham. He's the research lead at Health Via Modern Nutrition. They produce Ketone IQ. And I like Lat because, as you just heard, he not only talks to talk, but he walks the walk, so he kind of understands how this stuff feels, I think. During our last episode, didn't we, like, challenge ourselves to see how many ketones we could actually drink flat?

Latt Mansor [00:03:25]: We did. We did. We. We drank for at least like, four or five shots during the entire interview, I think.

Ben Greenfield [00:03:32]: Yeah, we made it through almost a full bottle of, like, the big one.

Latt Mansor [00:03:37]: Yes.

Ben Greenfield [00:03:38]: Yeah. Which is interesting because a lot of people say, because the ketone in that is one three butane dial, that we should have felt drunk. Yeah, I didn't like. I. I've felt. I felt fine.

Latt Mansor [00:03:49]: I don't know what 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, you know, 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.

Ben Greenfield [00:04:14]: If I'm going to overdose on glucose, I want to do it on Cinnabon. I'm just saying 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, you know, fasting, carb restriction, a ketogenic diet, et cetera, that give you something that ketones can't?

Latt Mansor [00:04:58]: Yes. Okay, let's. Let's go back to ketone one on one, like what we did before, just, you know, 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, that is ketones.

Ben Greenfield [00:05:36]: 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.

Latt Mansor [00:05:54]: Thank you. Yes, that's. That's the whole point. Yeah. 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 your 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 [00:06:19]: 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?

Latt Mansor [00:06:30]: 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 five 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.

Ben Greenfield [00:07:20]: So let's say you or a loved one were at risk, God forbid, of a heart attack. Like 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.

Latt Mansor [00:07:32]: Exactly. Hypoxic stressful event. Like a lot of heart complications, it's because of the deficiency in energy, right? Deficiency in either glucose or deficiency in some form of blockage in the, in the arteries, causing deficiency 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, 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.

Ben Greenfield [00:08:10]: 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 eight 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. Um, now I interrupted you as you were going to the differences between a ketogenic diet and drinking yourself into ketosis.

Latt Mansor [00:08:42]: Right. So if you are on your own, you know, 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 six to eight 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 that. There goes your question earlier. Is there any conditions or any benefits that the ketogenic diet or the endogenous ketones can have that ketones 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.

Latt Mansor [00:09:42]: 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?

Ben Greenfield [00:09:54]: 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.

Latt Mansor [00:10:44]: Yeah, it's the same as taking Ozempic.

Ben Greenfield [00:10:46]: Right.

Latt Mansor [00:10:46]: Like Ozempic severely restrict your, your appetite and therefore you are eating less and then you lose weight. Right. So, so it's, it's not that Ketone IQ is going to be your, your magic pill that you know answers to all your, 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, put them in a deeper ketosis state and then two, to enhance or augment the appetite suppression aspect of things, especially when they are on calorie deficit, a lot of them, they will experience fatigue. And as you and I know, we do a lot of like 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 the speech.

Ben Greenfield [00:11:40]: 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 seven calories per gram?

Latt Mansor [00:11:56]: Yeah, it is 70, 70 calories per 10 grams. Yeah. So seven, seven per gram.

Ben Greenfield [00:12:01]: 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.

Latt Mansor [00:12:11]: 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 Ketone IQ made it a breeze.

Ben Greenfield [00:12:24]: 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?

Latt Mansor [00:12:45]: Great question. Now, the main form of ketones that our body use for energy and being transported throughout our body is beta hydroxybutyrate, which is, 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 you know, molecular wise. BHB is. BHB is BHB and your body will recognize it the same and will utilize it in the same exact way.

Ben Greenfield [00:13:30]: 1,3-Butanediol from Ketone IQ would go through liver first, it 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.

Latt Mansor [00:13:44]: 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 ketones, you are measuring blood BHB. So if you're on ketos 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 [00:14:05]: 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?

Latt Mansor [00:14:12]: Great question as well. Because BHB is in the form of free acid. It's either because it's literally acid. So we, 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 GI irritation was too much.

Ben Greenfield [00:14:39]: I have some bottles of pure concentrated BHB in my refrigerator that I occasionally use. And the taste goes away after about three hours. It's pretty intense.

Latt Mansor [00:14:48]: It's very extreme because it's just acid. And that's why people create ketone salts, right? 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-Butanediol. But it's a great question because why, why don't you directly take the molecule itself. But the reason is because it's too acidic for your GI.

Ben Greenfield [00:15:15]: 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.

Ben Greenfield [00:15:50]: You're drawing a lot of water into the intestines.

Latt Mansor [00:15:53]: 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.

Ben Greenfield [00:16:03]: 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 show that the brain with the presence of glucose versus the presence of ketones will preferentially turn to the ketones as a fuel source?

Latt Mansor [00:16:30]: I believe so. But there is one study by Muyeka Perodi 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 function of 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. 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.

Latt Mansor [00:17:10]: Because if you think about it, brain's brain has a lot of fat, 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.

Ben Greenfield [00:17:30]: Is it true that breast milk is rich in medium chain triglycerides? And that would be a way it could support that.

Latt Mansor [00:17:35]: 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 [00:17:46]: 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. 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?

Latt Mansor [00:18:19]: Oh, yeah, absolutely. I. 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 is 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.

Latt Mansor [00:18:44]: So it is very possible that every part of our bodies are metabolizing different fields at the same time. It's just at different rates.

Ben Greenfield [00:18:53]: 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?

Latt Mansor [00:19:21]: Yes, we have seen so far the studies have been on ketone ester. So that's it. For transparency sake, ketoneurs have shown increase in cognition in athletes. And also in our $6 million contract that 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, 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 you to NICU and then give them more cognitive test.

Ben Greenfield [00:20:18]: I mentioned earlier that I wanted to ask you about how professional sports teams are using ketones. You even see like if you watch the Tour de France, they're handing them things to drink before and after. Do you have any inside knowledge of like how they're actually using these? Like before, during, after, how much? Anything like that?

Latt Mansor [00:20:37]: Sure. I mean we have been partnering with Visma Lease a Bike. I mean they, they just sort of won Tour de France last year. No, the year before. And they, 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 out every two hours. But for Visma, for 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.

Latt Mansor [00:21:10]: 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.

Ben Greenfield [00:21:22]: 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?

Latt Mansor [00:21:35]: You mention 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, you know, 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.

Latt Mansor [00:22:10]: And then on top of that we have also seen when people take ketones after exercise, they increase glycogen resynthesis, increase MTO activation for protein synthesis. And recently we are just wrapping up a study from KU Leuven with Chiel Poffé, one of the, one of the bigger names in the ketone research world and he basically conducted a study with Ketone IQ looking at recovery angiogenesis and epoxy, by the way, some people might.

Ben Greenfield [00:22:40]: Not know what that is, so you might want to explain those terms.

Latt Mansor [00:22:43]: 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. The 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 [00:23:27]: Wow. And that list of effects that you mentioned, you talked about increased MTOR activation leading to increased muscle protein synthesis, which we call an 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.

Ben Greenfield [00:24:18]: Have you thought about that?

Latt Mansor [00:24:19]: Yeah, that would be. That would be the next step, the expansion of that, 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, you know, 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 diaster, another form of ketone ester, in preventing muscle loss in cachexia in cancer patients. So that has also been shown to. To mitigate muscle loss. So not only you can sort of keep the muscle, you could potentially increase muscle, muscle growth if you use it correctly.

Ben Greenfield [00:25:11]: All right, so the sleep part. What about the part.

Latt Mansor [00:25:14]: 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, you know, 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 [00:25:43]: That's interesting. And a lot of these sleep studies on exercises impact on sleep parameters. You'll see the sleep or the exercise done in the early evening or three hours or so prior to bedtime. Do you know what time people were doing this vigorous exercise?

Latt Mansor [00:25:59]: I can't recall exactly what time.

Ben Greenfield [00:26:02]: 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 on 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.

Latt Mansor [00:26:32]: That is correct. And on top of that, on top of that, we have currently an NIH grant in collaboration with John 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.

Ben Greenfield [00:26:53]: Huh, Interesting. I wonder why that would be. Would it be because there's lower oxygen need in the presence of ketones?

Latt Mansor [00:26:59]: 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 reduced 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.

Latt Mansor [00:27:32]: But with ketones present. We have seen the previous paper which use ketogenic diet. They saw an improved cardiac 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 Ketone IQ to emulate the same effect.

Ben Greenfield [00:27:56]: 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?

Latt Mansor [00:28:13]: 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 butanediol 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.

Ben Greenfield [00:28:44]: You mean that the food would somehow, like, slow the absorption rate of a BHB?

Latt Mansor [00:28:48]: Yeah, it could be. Or the. The 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.

Ben Greenfield [00:29:06]: Okay, I have a little bit of a biochemical conundrum I want to throw at you.

Latt Mansor [00:29:10]: Sure.

Ben Greenfield [00:29:10]: 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 50's. 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 write a blood glucose of 50 to 60 in the absence of ketones. Explain to me what's going on here.

Latt Mansor [00:29:58]: What kind of breakfast do you have?

Ben Greenfield [00:30:00]: I have a smoothie. It doesn't have a lot of carbohydrates in it. Sometimes a little bit of blueberry.

Latt Mansor [00:30:04]: Okay, so it's not like a breakfast devoid of carbohydrate. Right.

Ben Greenfield [00:30:09]: 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.

Latt Mansor [00:30:27]: 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, you know, 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 glucose. My glucose. 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.

Ben Greenfield [00:31:02]: That's the term. I've heard others describe this as reactive hypoglycemia.

Latt Mansor [00:31:05]: 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 of react to it in an exaggerated way.

Ben Greenfield [00:31:22]: 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.

Latt Mansor [00:31:38]: Exactly, exactly.

Ben Greenfield [00:31:39]: And then if you're in that low carb state. Hence the ketones.

Latt Mansor [00:31:42]: Right, Hence the ketones. So ketones also lower glucose postprandial. But that is a complete different mechanism of action. What, 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.

Ben Greenfield [00:32:18]: Right. Gluconeogenesis, as the name implies, and the liver is engaged in that frequently.

Latt Mansor [00:32:24]: 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 to 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.

Ben Greenfield [00:32:59]: Yeah, yeah. So back. 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.

Latt Mansor [00:33:14]: Yeah. Look at Dr. Jonathan Little's work from University of British Columbia. He, 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 [00:33:30]: Okay. And in terms of how long someone could have elevated ketones after drinking, let's say a standard serving, say like 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, kind of have that mental edge or have the elevated ketones?

Latt Mansor [00:33:50]: 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 six hours. And if you're working out, it may last for like maybe two to four hours. So obviously you, 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.

Ben Greenfield [00:34:29]: They are sedentary, they say I'm burning the ketones off. 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, you know, 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.

Latt Mansor [00:34:59]: That's a great point. Because 70 calories, you know, people like, like, like you for example, you burn it in 15 minutes. So it's like what, 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 they have, what, 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 ketone metabolism.

Latt Mansor [00:35:53]: So when you are burning your own fat and you're already low on, on, on sugar, obviously some of the fat will also get converted into ketones and that makes ketone metabolism more efficient.

Ben Greenfield [00:36:04]: I think. 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.

Latt Mansor [00:36:47]: That is correct. That's exactly what I would answer.

Ben Greenfield [00:36:51]: Huh, that is so cool. So basically it's almost as though I'm jump starting my body's own fat burning process by like having a shot of ketones and then exercising.

Latt Mansor [00:37:01]: 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.

Ben Greenfield [00:37:09]: Yeah. Is that GLP-1 based, that appetite suppression effect?

Latt Mansor [00:37:13]: It's very interesting. A lot of doctors actually believe that it has a GLP-1, 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 will be very, it'll be a very interesting study.

Ben Greenfield [00:37:33]: Now for athletes, you know, 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 like exercise science called the dual fuel type of approach, where you simultaneously elevate glucose via, let's say like 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.

Latt Mansor [00:38:02]: I think it's good because you are providing your body the option. Right. Because your body will always choose the most efficient fuel. So same thing with how we advise our athletes who are not keto adapter, 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. Right. 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 [00:38:48]: 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 like a four hour marathon, I wouldn't necessarily have to bring like four bottles of Ketone IQ out there with me, especially if during exercise it might give me two to four 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.

Latt Mansor [00:39:18]: An exact protocol that we would ask people to do. We would ask them to take half an hour before and then top it up an hour and a half into your workout, which is two hours since the first dose, and just top it up once and then if you finish the race. That's it, that's the two doses?

Ben Greenfield [00:39:34]: 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 we're 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 that this is in research or anything like that?

Latt Mansor [00:40:07]: 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, you know, be considered the fatty acid line, which is not, you know, the glucose glycolysis line well 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, as hard as they could for 10 seconds, rest for 30 seconds and repeat that for five times. So they do that for five times.

Latt Mansor [00:41:05]: And what we have found is very, very interesting. We found that they are, 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 [00:41:25]: And by, 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 remember, I'm trying to remember now.

Latt Mansor [00:41:38]: Yeah, 1.0.

Ben Greenfield [00:41:40]: That would be like full carbohydrate utilization.

Latt Mansor [00:41:42]: Yeah. So. So all these people, all these participants. Participants are both one, 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, they would perform worse than the placebo group. But they perform better.

Ben Greenfield [00:42:08]: They're burning glucose less. So.

Latt Mansor [00:42:10]: Yeah, exactly. But they are performing better. So what we think is happening here could be an analgesic effect on the brain.

Ben Greenfield [00:42:18]: Like influencing the rating of perceived exertion.

Latt Mansor [00:42:21]: Exactly. So they are feeling less painful because these exercises are meant, are designed to elicit. 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.

Ben Greenfield [00:42:47]: 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 relate to performance and I guess longevity and anti aging. You see guys like Brian Johnson doing 60 days in 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 Celgem 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?

Latt Mansor [00:44:02]: It's funny you mentioned that because I just recorded a few weeks ago with Gabby Reese at her house and she has a two 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 hypoxia, the sensate, the sensing of oxygen via HIF, which is the hypoxic inducible factor, is a factor that is 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 a 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.

Ben Greenfield [00:45:05]: 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.

Latt Mansor [00:45:49]: 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, you know, a very great like big paper, high impact factor paper showing the, 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 fat form of prophylaxis or prevention against colorectal cancer.

Ben Greenfield [00:46:31]: You know, 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, this is very interesting to me. It just kind of makes me want to, you know, as you know, I've been kind of on the ketone bandwagon for like 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.

Latt Mansor [00:47:00]: Yeah, but my. Check out, check out the paper. I think you'll find it very interesting because.

Ben Greenfield [00:47:04]: Yeah, I have a mark I'm going to put in the show notes too. It's on nature, right? That one.

Latt Mansor [00:47:07]: Yeah, yeah, yeah, yeah. And they even like reverse it. They when they put the animals, 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 [00:47:29]: 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 like the peach mango flavor, I think the green apple, the regular, you have the big bottle.

Ben Greenfield [00:47:48]: Any other innovations coming down the pipeline?

Latt Mansor [00:47:51]: I think we are just, you know, 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 like almost a decade.

Ben Greenfield [00:48:03]: Right.

Latt Mansor [00:48:03]: We've been knowing the area. I think for the general population who have not heard of Ketones, the tastes have always been the barrier. Therefore, our innovation would be to improve the flavor and really compete in the five 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. 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 a 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.

Ben Greenfield [00:49:06]: 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 that the key is the caffeine just for a little extra edge?

Latt Mansor [00:49:22]: I think there are some studies that may show improved effect. My hypothesis is that, like I said, caffeine increases your brain energy demand and ketone provides that energy supply. So that's why it's synergistic. So in terms of how effective that is in a performance and all that, I think we need a whole study for that.

Ben Greenfield [00:49:47]: Yeah. Yeah. Okay, cool. And it is the green apple flavor. That's a caffeine one, right?

Latt Mansor [00:49:50]: Yeah, Green apple. We have the peach as well. I think this week we are releasing the raspberry lemonade. It's gonna. Yeah. So gotta send you some.

Ben Greenfield [00:49:59]: I mean, if you really wanted to appeal to the, you know, to the keto enthusiast at heart, you develop like the old flash and flavor with the spot splash of liquid gasoline. You know, for those of us who just crave that acidic. Yeah.

Latt Mansor [00:50:10]: I mean, I have this big bottle just sitting by my desk. Like, I still drink this because it's easier to. To pour out like two doses.

Ben Greenfield [00:50:18]: Yeah. Yeah. Wow. I love those big bottles, by the way. They were. They're pretty easy to just accidentally drink half the bottle though, before half the day was over.

Latt Mansor [00:50:25]: But just sip on it.

Ben Greenfield [00:50:26]: Yeah, exactly. All right, so all the show notes 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/D R L A T T, that's BenGreenfieldLife.com/DrLatt for the show, notes. 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 one three butane dial.

Latt Mansor [00:50:57]: Hey, you know, anytime you I'll be there right away because you know, I enjoy the food that you make and, 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 what you're playing with these days.

Ben Greenfield [00:51:11]: Okay. You have my word. The 3P at my new place in Idaho. You're going to love it. You're. You'll drool.

Latt Mansor [00:51:16]: Yeah. So you'll just let me know when I'll book my flight.

Ben Greenfield [00:51:20]: All right, folks, I'm Ben Greenfield along with Dr. Latt Mansor, signing out from BenGreenfieldLife.com. have an incredible week in the shownotes are at BenGreenfieldLife.com/DrLatt to discover.

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