Danny Jones Podcast - #124 - How to Reverse Human Aging | Dom D'Agostino

Episode Date: February 7, 2022

Dr. Dom D'Agostino returns to the podcast for round 2! On this episode we discuss Dom's research on Hyperbaric Oxygen therapy, metabolic health, the ketogenic or 'keto' diet, weight lifting, anti-aging, NAD therapy, and much more!  https://ketonutrition.org  https://www.instagram.com/dominic.dagostino.kt  https://twitter.com/DominicDAgosti2 help us make more money: https://bit.ly/koncretepatreon sponsors  https://liquiddeath.com -  Use code KONCRETE at checkout to get a free koozie 2-pack with a 12-pack purchase. danny  https://www.instagram.com/jonesdanny  https://twitter.com/jonesdanny Learn more about your ad choices. Visit podcastchoices.com/adchoices

Hello, world. Today's guest is episode two, part two, with Dom Degistino. Dom is a research scientist for the Institute of Human and Machine Cognition. And the primary focus of Dom's laboratory is developing and testing metabolic-based therapies, including ketogenic diets, ketone supplements, and metabolic-based drugs. Dom's research has also been supported and funded by the Office of Naval Research and the Department of Defense. Please welcome Dom Degistino. Thank you for coming on the show again, man. Really appreciate it. You've been on here before, but for the new listeners and viewers, why don't you let them know what you do? Yeah, I appreciate being on. Thanks, Danny. Absolutely. Yeah, I was trained. My formal, like, education is neuroscience. Well, it was nutrition as an undergrad, and then I gravitated to neuroscience and physiology, where I studied the neural control of

autonomic regulation, so the brainstem mechanisms of how and why we breathe. And there was oxygen and CO2 chemoreceptor regions sort of. I can push a little closer, just a little bit, push the mic a little bit closer to you. Closer, yeah. And so my research on the neural mechanisms of respiration led me to, to diving physiology. So I was an avid diver, you know, during my PhD.

And that led to opportunities to do my postdoctoral fellowship. in diving physiology, specifically funded by the Department of Defense, Office of Navy Research, where I did work on looking at oxygen toxicity seizures, which limits Navy SEAL diving. And I spent quite a few years developing hyperbaric technologies and testing these technologies in biological systems to understand how hyperbaric oxygen works. and how the benefits, but I was actually really focused on the negative consequences of being exposed to very high levels of oxygen. And then that topic led me to the ketogenic diet because ketones are neuroprotective,

and then the ketogenic diet was actually used as an anti-seizure, anti-convulsant therapy and oxygen toxicity seizures, which limits hyperbaric oxygen. you can't go above, for example, three atmospheres of oxygen with hyperbaric because you have an oxygen toxicity seizure and also for military diving. It's a limitation. So I was very excited at this point in time when I discovered the ketogenic diet, which I studied nutrition as an undergrad, but never knew the ketogenic diet was actually developed for epilepsy and for seizure disorders. So it gave me the opportunity back about 15 years ago to steer my research away from drug research into studying the neuroprotective effects of this, you know, high fat diet, which it was not a very good career move if you're going into academia and that your whole part of being in academia is to pull in federal dollars to advance your research programs. and putting a lot of time and effort into studying a high-fat ketogenic diet. There was no funding for this.

But I knew it worked and I knew there was good science that could be done to support this approach. And then that springboarded my sort of path to where I am now. And you're at USF, right? Yeah. Yeah. University of South Florida, specifically the Morsani College of Medicine. And I also have an affiliation with the Institute for Human and Machine Cognition, or IHMC. And so I work in different capacities through those two institutes.

One of the things I wanted to talk to you about was you said a lot of your studies are in hyperbaric. And is that specifically hyperbaric oxygen therapy? Yeah. Yeah, well, yeah, hyperbaric oxygen, like at a fundamental basic science level. Okay. So we do, I originally started the first project that I had was pretty esoteric, is developing hyperbaric atomic force microscopy. And atomic force microscopy will give you like the scanning resolution of electron

microscopy, but you can image living tissue with it and cells. So we were using this technology and then part of I spent a number of years putting a hyperbaric microscope inside of a customized an atomic force microscope inside a customized hyperbaric chamber and then using it on a variety of different cell types. So the question is the question that, you know, the military was funding us for is like essentially what happens to cells inside the cell when you hit. it with a high concentration of oxygen. We never knew the answer to this because no one had a hyperbaric, you know, microscope, right? So I started my research on looking at cells, looking at mitochondria, looking at like free radical production in cells, mitochondrial function and things like that with muscle

cells, brain cells, cancer cells, human dermal fiberglass cells and doing a lot of research there. And then later, I was able to get more funding and expand. hyperbaric oxygen research into animal models, where we were looking at not only seizures, but also looking at cancer. And we published a number of studies on using hyperbaric oxygen as a means to further augment different cancer, anti-cancer protocols. And that would be with nutritional ketosis and other things we're working on in the lab. So, and then, you know, a couple years after doing animal research, we got funding as a subcontract working at Duke. At Duke,

they have an amazing environmental research facility that NASA uses and military uses where we have subjects on a ketogenic diet that are being put inside hyperbaric chamber. And they use, we're taking, we're getting tons of data from them, blood data, blood gases. They go in on a standard diet, then they go in on a ketogenic diet with ketone supplementation, and then we look at their cognitive function, their reaction time, they play a video game simulator, they're exercising, like it's like probably the craziest setup you can think about, and we push them to the edge of a seizure by giving them a very big dose of hyperic oxygen, and we monitor their brain activity through EEG, and then we essentially decompressed, like right before they're going to get hit by a seizure.

So we have sort of ways to predict it. So there's that. So we moved from cells to mitochondria to cells to animal studies and then to human clinical trials, which is a registered clinical trial on clinical trials.gov. And then I myself and my wife were involved with an undersea mission where we lived in a hyperbaric environment for me. It was 10 days. And my wife was 9 days.

And that's the NASA Extreme Environment Mission Operations, which is a hyperbaric mission, where you live in saturation. And if you live in saturation more than 24 hours, you become an aquanaut. So both of us have became aquanauts. Just from our research background, our diving background, we were selected for that mission, where we get to train with astronauts. It's part of the astronaut training program. Oh, wow.

So we get to work with, and my crew member or my commander, Dr. Shell Lingren, and Samantha Christopheretti, who's an E, European Space Agency astronaut, they were just selected to go up in in April, I think, to ISS. So they were both Nemo Aquanauts with us. So yeah, the hyperbaric stuff has been very interesting. We went, you know, from cells to to mitochondria, tissues, animals, different types of animal models, to human clinical trials, to being research subjects ourselves, or we're doing research, you know, on human subjects where we are the subject in a hyperbaric environment. So that's, I don't really talk about it that much. Hyperbaric research is a big

part of what we do. And people know me as the keto guy or ketogenic diet guy, but that's very much interconnected with the hyperbaric world because ketosis is neuroprotective and has antiseach effects. One of the reasons I want to talk to you about that is because a really close friend of mine just bought a hyperbaric chamber for himself. Like it's one of those consumer hyperbaric chambers that like the ballplayers using stuff. And it's supposed to come in this week. And he had to get an actual prescription written to buy it. And it made me curious.

I'm like, are there, are there any negative effects to use in these hyperbaric chambers? And like, are they, do you have to regulate yourself or is it okay to just get in this? Because I plan on using his hyperbaric chamber. Is it okay just to use it whenever you want? Or is there, is there risks involved? Yeah, well, I would highly recommend, you know, getting hyperbaric medicine guidebook, which tells you, so the oxygen is a drug. And if, you know, right now we are breathing 20% oxygen. So, you know, roughly, roughly speaking, 20.6%. So, and the rest of it's nitrogen. So most of our, our breath is actually

nitrogen that we're breathing a little bit of CO2, a little bit of argon, some gas. So, if this room was filled with oxygen, 100% oxygen, and we were kept in here, and you came back three days later, we'd be dead. And that's not even a hyperbaric pressure, right? So if you replace this room with oxygen, yeah, we would die. We would get something called pulmonary oxygen toxicity. Our lungs would just start, like, blowing up because it's producing oxygen-free radicals. And we would have edema, and we would die a very painful death. So you have to understand oxygen's a very powerful drug and at hyperbaric pressures, which means we are at one atmosphere of oxygen now when you increase the barometric pressure to two atmospheres and then go to

three atmospheres. That's every atmosphere is 10 meter of seawater or 33 feet. So if you were to dive down to 10 meters or 33 feet, that would be two atmospheres. Another 10 meters, you know, 66 feet. It would be three, three atmospheres. At that hyperbaric pressure, happens is the oxygen, your hemoglobin's already saturated, right? But because of the increased barometric pressure, the partial pressure of oxygen would increase. And you actually get more oxygen into the plasma independent of hemoglobin. And that would cause the partial pressure of oxygen in your tissues and your brain to skyrocket. And that produces oxidative stress. and that would kill you if you sustained it for a long period of time.

So which happens in different military dives and things like that. So you have to adjust the ratio of nitrogen to oxygen, in some cases, helium and other breathing gases. So getting back to, you know, you have a hyperbaric chamber. So my question would be, is it a hard shell chamber? Because a hard shell. A soft one. Soft shell. Okay.

So a soft shell chamber would really only go to about 1.3 atmospheres. So what that means is it can only basically take you to a quarter of an atmosphere higher than we're at now. So it's probably made out of a polymer, like a Kevlar, even bigger, different ones. So the chances of you hurting yourself, you know, are far less likely. But if you're just... I'm going to pull up the receipt for it. Keep going. Okay.

Yeah. If you were to stay in that hyperbaric chamber for a protracted period of time, then you could potentially, you know, damage your lungs. you're not going to get oxygen toxicity seizures or CNS oxygen toxicity, which is it called, because you need to be essentially at a higher pressure, which would involve a hard shell chamber. So a lot of the work that we do, I mean, we have chambers that go to like 60, 70 atmospheres. We have, you know, a lot of what we do is within the military diving operations of about five atmospheres and above. And, but, yeah, there's, you know, I study the negative effects of hyperbaric oxygen and that by looking at the various mechanistic things that hyperbaric oxygen does, like, you know, enhances wound healing, it decreases inflammation, it activates stem cells.

Most of the people who email me are people who are using hyperbaric oxygen to enhance their athletic performance to speed recovery. They use it as a like a neotropic. So oxygen as a drug to increase, you know, growth factors in the brain like BDNF. And, you know, research was done to demonstrate, and I think this research was done by a colleague of my Dr. Steve Tham when he was at University of Pennsylvania at the time. He showed that hyperbaric oxygen can increase stem cell production and then the release of stem cells. So there are various drugs that people take to increase stem cell production or you could use altologous stem cells, you know, and inject them into yourself. Or you could undergo hyperbaric oxygen therapy and actually get your body to coax your body to generating more stem cells.

So that can aid that stem cells tend to get into circulation and then they they hone in on areas that are damaged or inflamed and then it augments recovery from there. So it could be internal things as well as external wounds, basically. When you say wound healing, what do you define as like a wound? Yeah, so there's about 14 different FDA approved applications for hyperbaric oxygen, and the big one is probably wound healing. So if a facility around here, if you just search where are hyperbaric chambers around here, they're using it for mostly diabetic wounds for people who are overweight, and they have a wound like on their foot.

And that because many people are overweight or they have diabetes, that impairs blood flow to the area where a diabetic wound becomes resistant to healing. And when you give hyperbaryxygenates the wound and reverses hypoxia. So it facilitates the, you know, it increases the partial pressure of oxygen at the wound site. And by doing so, it increases energy within the wound. So energy production could be down by 90% like in an ischemic wound. But when you hit it with oxygen, then you're stimulating ATP production, which is like our energy currency and stimulating metabolism,

and the wound can then heal. And then it has, so it's used mostly for wound healing gangrene. There are anaerobic bacteria that grow in situations where there's not a lot of oxygen. And you can get an infection and gas gangrene can kill you. And the only thing that we know that can kill this anaerobic bug is hyperbaric oxygen. It's also used for decompression sickness if you're diving, like even in recreational diving and you stay down too long. It's stay down too long and you pop up to the surface. The nitrogen's still in your system and the bubbles are going to want to come out.

It's called the bends underwater if you come up too fast. But decompression sickness will kill you. You can get an air embolism in your lung or your brain. So if someone pops up to the surface too quick because they have some kind of emergency or there's something, that person needs to go inside a hybrid chamber and be slowly decompressed. So the chambers around here, 90% of them are used for wound healing and then also for diving for reversing decompression sickness and carbon monoxide poisoning. If you have carbon monoxide poisoning, a way to save a life is the only way to do it is really

with hyperbaric oxygen. So these are some of the applications. And there are many, including for cancer, for like wound healing, if you have radiation, if you're being treated with radiation that caused radiation necrosis, and hyperbaric oxygen can reverse and heal that tissue that has been radiated by radiation. So that becomes a way where patients can conceivably, if they've had radiation therapy, they could get a prescription for hyperbaric oxygen. And the prescription, you mentioned a prescription, that's usually for levels of oxygen that are above 1.4 atmospheres, like 2 or 2.5 or even 3 atmospheres. Really? Yeah, because that would require a hard shell chamber.

Yeah, this is called a respiro. Respirro. And do you know the-it's this thing right here? The working pressure of the chamber. Oh, yeah, that is a soft shell chamber. Yeah So yeah I mean if you're gonna get that and have it installed in your house

There are certain regulations you need to follow And you know you might have to have a hyperbaric Tech come out and set it up because you know you don't want to mess around with oxygen If you were to get a hard shell chamber Then that's a whole other set of regulations and guidelines that you have to follow But you know most of our research have been done within the pressure range that would require a hard shell chamber, but I do believe that there's a lot of benefit that you can get from these soft shell chambers. And it's quite a bit safer, too.

Yeah. That's the one like LeBron uses. I know. I've seen videos of him using that one. Yeah. Yeah. So he's using it to like augment his recovery. Like in between when he has like the playoffs, when they have a game every other day.

Yeah. He's spending, you know, 40 minutes a game sprinting up back and forth on a full court. I think he uses that on his off day to kind of like speed up his recovery because I'm sure there's a lot of wear and tear on your muscles and joints and stuff. Yeah, so I communicate with a number of NFL guys. Even I think around here, Vinnie Testa Verdi is around here. Okay. I remember he came to one of my talks actually at the College of Medicine at USF and it was he was pretty cool to talk with. I think he has his own hyperbaric chamber.

Yeah, I communicate with quite a few NHL, NFL guys, you know, military guys that are using it to speed recovery. And LeBron James, I think he's on a keto diet too, or low carb diet, I think. Really? Yeah. Well, I mean, like low sugar, low, I mean, a lot of these guys, I haven't personally, but I've communicated with people who, you know, have coached him in some ways. Yeah, I have heard things about his, I've heard people talk about, people who are close to him,

talk about, like, what his diet is. and I've seen videos of him talking about when he, especially like when they're in the playoffs towards the end of the season when it's like coming down to the line that he really, really goes out and he cuts out carbs, eats a lot of steaks, a lot of high fat stuff, and completely cuts out sugar 100% as well as the oxygen. So I don't know, I know he spends, he's known for spending more money on his body than any other athletes. He claims he claims over a million dollars a year on his body specifically, whatever that means.

That's easy. I mean, because there's, I mean, there's a lot of drugs and stuff, too. I guess you could take to enhance performance that, but these guys have to, I don't know how they get tested, but for supplements, it has to be NSF, you know, certified to be used. Yeah, there's a lot of things that you could do. A lot of it's untested and, you know, not really a lot of science to back it up. But that's really just because there's not a whole lot of funding to go into evaluating, various technologies for enhancing athletic performance. Many of these things are, you know, hyperbaric oxygen has been, all the funding goes to wound healing.

Like, you know, managing is a multi, multi-billion dollar health care problem right now. I mean, it's been, and we don't have anything to basically speed wounds. We have, I had a PhD student that worked under me that looked at eschemic wounds, and one of the biggest things that enhanced the wound healing process was the ketone supplements, ketogenic diet and ketones supplements. So all the wound healing technologies and patents out there are about putting things on to wound to augment wound healing. But when we change our metabolic physiology, we are lowering blood glucose, lowering insulin, reducing inflammation. So that speeds greatly enhances blood flow by like.

like 20 to 30 to even 40%. And then the ketogenic diet or even exogenous ketones increases something called adenicin. Adenicin is a vasodilator. So we get more blood flow to the region. And that blood that's flowing into the region has ketones. And ketones are metabolic substrates that can reactivate cells. And they have anti-inflammatory effects. But when you increase circulation and you have ketones in circulation and you're reducing glucose,

which could be pro-inflammatory, when glucose is low, Ketones are elevated, right? If you take, if you're on a ketogenic diet or you take ketone supplement. So those ketones can then, uh, kind of aid in that, uh, enhancing the metabolic state of the wound, which is really the definition of impaired wound healing is that there's low, uh, energy state, low blood flow. And, uh, yeah, we're sitting on some papers now. I need to get out, but she did her PhD dissertation on that. And when that's coupled with the ketogenic, with hyperbaric oxygen when you couple ketone supplementation or the ketogenic diet with hyperbaric oxygen, that's greatly enhancing the wound healing process. And one could extend that. When we work out,

we are basically, you know, you're trying to enhance wound healing. You know, your body is banged up. You know, tissue is damaged. And then you have tissue remodeling. That's part of the adaptive process to training when we train a muscle. We break it down. And the adapt. And the adapt. adaptive process of training is skeletal muscle protein synthesis, remodeling, and then the faster we can do that, the faster we can get back into the game. And you talked about like the stem cell production and stem cell release, especially when it comes to, I can understand how it can help heal people that are affected by radiation and chemotherapy when it comes to cancer. could it be used as a replacement for chemotherapy or radiation to any extent? I know it's obviously scientifically not there yet, but do you think that's a possibility? Well, there's a couple things to, like, you know, to answer that question.

When people do undergo chemo and radiation, sometimes their blood counts drop, like a certain, their hematicrit drops and white blood cells drop. So, and stem cells can drop too. And hyperbaric oxygen could be a way to augment that. If we have, the Israelis showed that with hyperbaric oxygen, that it can actually increase HIF 1 alpha, which is counterintuitive because HIF1 alpha is hypoxie inducible factor alpha. When we undergo hyperbaric oxygen and then we come out of the chamber, our body senses

relative hypoxia just because of the relative changes and that can stimulate hip one alpha and then maybe actually increase our red blood cell count. So some athletes may do hyperbaric oxygen to actually increase their red blood cell count. So that's a little bit peripheral to the conversation. What does that do? To increase a red blood cell count, what does that mean? Yeah, oh, that means like you have more red blood cells so you have greater oxygen carrying capacity. And so athletes, especially like cyclists and, you know, elite level cyclists, one of the go-to-drugs in that world is erythropoetin or EPO. And then EPO will increase your red blood cell count. That increased something called your hematicrit.

And ultimately, that's giving your body an advantage because you can carry more oxygen. Okay. So hyperbaric oxygen may be able to do that. And it's nice that you're augmenting your own physiology. to increase the production of those cells. But your question with cancer in that, so we know radiation and chemotherapy work by, work in killing cancer cells by augmenting reactive oxygen species

or oxygen-free radicals, right? We know about free radicals. So with radiation, if you apply radiation to a tumor, the radiation nixed the DNA, and that's one way to kill it, but most of the radiation damage is actually a result of increasing oxygen-free radicals, right? So that's how radiation primarily works. Chemotherapeutic agents that kill cancer cells kill cancer cells by increasing oxidative stress in the cancer cells.

But it does it, both of these modalities are chemotherapy and radiation are very potent carcinogenic agents. So we are using a potent carcinogenic modality to kill cancer cells, right? And it's doing it primarily through augmenting something called oxidative stress, you know, or oxygen-free radicals. So hyperbaric oxygen is a way to naturally, by increasing the partial pressure of oxygen in our body and reversing tumor hypoxia, as a tumor grows, it outstrips its ability to supply oxygen because the blood vessels can't keep up to the expanding biomass of the tumor.

So the core of the tumor often becomes hypoxic. And when you put someone inside a hyperbaric chamber, that does a number of things. It reverses the tissue hypoxia inside the tumor. So the low oxygen in the tumor is reversed with high oxygen, hyperoxia. And when you hyperoxygenate a tumor tissue, that causes a mass. massive burst in oxygen-free radicals for a number of reasons. The oxygen can get in the tumor because the oxygen is not being carried by red blood cells, which get caught in the little blood vessels.

The oxygen is actually dissolved into the plasma, independent of hemoglobin. So this is very important because the pressure component of hyperbaric oxygen, which means the increase in barometric pressure, literally pushes the oxygen into the plasma. and then it could get into the little nooks and crannies, if you will, of the tumor. And the tumor goes from, you know, a tissue P.O.2 of like two or three millimeters of mercury to like 150 to like 2,000 millimeters of mercury, which is very, very high. And when all that oxygen is inside the tumor, because the tumor is like a bunch of screwed up cells that are also degrading, you have a lot of heem, like heem proteins are. being degraded and you have a lot of free iron. And oxygen in the presence of free iron in that environment drives something called the fenton reaction. And then you have a massive burst of oxygen-free

radicals and it's driving different pathways that kick on cell death within the tumor. Now, this can happen in normal healthy tissue, but it's greatly augmented in cancer tissue because the cancer tissue's relative state is low oxygen. And when you reverse the tumor hypoxia and hyper oxygenate it, you get a correspondingly higher burst of oxygen-free radicals. It's because the relative change is going to be higher, right? And then the oxygen-free radicals feed into a pathway because of the free iron that contribute to more reactive intermediates like the hydroxyl radical.

and these things can help to essentially kill the cancer from the inside out. An important thing to note is that hyperbaric oxygen may further enhance the cancer killing effects of radiation and chemotherapy when they're done together. So, yeah, I believe that hyperbaric oxygen should be used for many different tumor types. And I think it has a lot of potential. I mean, in our lab, we coupled it with the ketogenic diet and saw that we could extend survival in mouse models of metastatic cancer. And that motivated us and many others. So when it hyper-oxygenates these tumors and you explained how the oxygen-prebridicles explode, what does that physically do to the tumor itself? The tumor will shrink.

Will it die? Like what happens to the actual tumor or the cancer tissue? Yeah. So if we're talking about a solid. a tumor and then you apply, you know, hyperbaric oxygen, for example, two to three atmospheres of oxygen for 60 minutes, three times a week, something like that. So that's a pretty, pretty big dose. What is happening to the tumor is that it's, you know, the tumor, like I mentioned, especially a growing tumor mass, becomes hypoxic. And then when you're in the chamber and

experiencing a high level of oxygen. And if you were to put an electrode inside the tumor and measure the oxygen, the level of oxygen would go up like 2,000 times. So when that oxygen gets super high in the tumor, it's stimulating the production of these free radicals, which then kick on a number of different pathways that can essentially rupture the mitochondria start spitting out oxygen, that creates oxidative stress. And then you oxidize. membrane lipids, you oxidize proteins, you oxidize nucleic acids. This creates a lot of stress to the cell. And then cells literally start like blowing up, rupturing. So when, yeah, so when I was, some of the early studies that I did was actually developing hyperbaric atomic force microscopy. And then later

I made it a laser scanning confocal microscopy unit to this microscope and it's inside the chamber. And we were looking at different cell types, and one of the cell types were glialblastoma cell types, which is a type of brain cancer. And this particular cell type was U-87, glialblastoma multiformi. So it's not super important, but it was derived from a patient, I think, a 44-year-old patient or whatever. So I had the cell line preserved. We plated the cells. We put it inside the hyperbaric chamber, and we were looking at them. And then we hit the cells with hyperbaric oxygen, and I noticed that the cell,

the mitochondria started pumping out tons of superoxide. I had a dye to measure that. And then I would see the mitochondria disappear. They were blowing up underneath the microscope. And as we were monitoring the fluorescent signal, which is the increase in the brightness of the cells corresponded to the production of oxygen-free radicals, as the cells became brighter, I saw the mitochondria disappearing. That means that they were blowing up.

They were rupturing. And then I started to see cells dying at a far faster rate than any other cell that I looked at, including smooth muscle cells, fibroblasts, human rat neurons, and different cell types. So I thought this was very interesting. And that was done maybe in 2007 and eight. And then a couple years passed. And I realized that this was an important observation. And no one made the observation ever because no one had.

a microscope inside a hyperbaric chamber. So I reached out to different people at the Moffat Cancer Center and then experts, you know, who studied cancer. And they said, what you're observing in these cancer cells is probably due to something called the Warburg effect. So Otto Warburg really was noted for, he got the Nobel Prize for his work on the mitochondria and mitochondrial respiration. And he had a theory on cancer that cancer was a metabolic disease and that impaired mitochondrial

activity, or what we call cellular respiration, impaired respiration would lead to compensatory compensation, glycolytic compensation. So the cells, as the mitochondria became defective, there would be an upregulation in glucose consumption and glucose energy pathway called glycolysis. So, you know, this, this, his whole theory kind of was hinged upon damaged respiration, so damaged mitochondria. And when I was recording from these cancer cells, I noticed that they had a lot of mitochondria.

There was no doubt that their mitochondria were working in some capacity. But I also noticed that when I increased the level of oxygen, the mitochondria had a rate of free radical production that was many, many fold higher than normal healthy cells, meaning that when we produce energy, when our mitochondria produce energy, and about, you know, 80 to 90 percent of our energy comes from mitochondrial oxidative phosphorylation, a consequence of that energy production is the formation of an oxygen-free radical called superoxide, and then that can go to hydrogen peroxide and ultimately potentially hydrogen hydroxyl radical to more reactive intermediates. So that superoxide is always being produced and it's like the exhaust on a car. You know, it's like the toxic thing that's being produced, but oxygen free radicals are also

signaling molecules. So there's a signaling function in addition to being a toxic free radical. So eliminating them completely is probably not a good idea. There's a balance, like a redox balance. So with the tumor tissue is putting. out proportionally far more oxygen-free radicals in response to the oxygen that I'm giving it. So giving tons of antioxidants are really not going to work because the mitochondria are already defective, right?

So what I was witnessing is that I was witnessing damage respiration and the mitochondrial. When we talk about respiration, we're talking about mitochondrial, you know, ATP production. Okay. It's like rest instead of respiring because they use oxygen. Okay. So with cancer cells, you have damaged mitochondria, and we call that their way of making energy is called cellular respiration or oxidative phosphorylation. And when you give the substrate for energy production, which includes oxygen, to the mitochondria, they produce proportionally more oxygen-free radicals, and they're essentially killing themselves from the inside out when you expose cancer cells to high-pressure oxygen. This is what we saw.

This is what I saw underneath a microscope. So it made sense to me that this was happening because of the Warburg effect, which means cancer cells have rates of sugar consumption that are like 100 to 200 times higher. And they're using sugar as a fuel for two different reasons. One is because the mitochondria are defective and there's impaired mitochondrial ATP production. Another reason cancer cells use glycolysis to get energy is that it feeds into a pathway of biosynthesis. So it's necessary for biosynthetic pathways to generate the expanding

biomass of the tumor. Using glucose in cancer cells, the cancer cells can also divert it to, it can increase the pentose phosphate pathway, which is a way that the cancer cells can actually increase their antioxidant capacity through this path. There's a number of different reasons, but the important thing to to know is that cancer cells have defective mitochondria, and because cancer cells have defective mitochondria, we can exploit that defect with hyperbaric oxygen by using that as a tool to further increase oxidative stress in selectively in cancer cells.

When we hit our body with hyperbaric oxygen, when we go inside hyperbaric chamber, we have an increase in oxidative stress all through our body, but our normal healthy tissues have the adaptive response that we can increase our endogenous antioxidant enzymes. So our tissues actually end up stronger because like exercise, when we exercise and do a super hard workout, and if we were to take our blood or take our tissue sample, you would see a lot of bad things going on. So that's actually the stress of exercise, right?

So the adaptive response that comes after that makes our tissue stronger and it upregulates a number of pathways. I mean, if you're training and lifting weights, you have skeletal muscle remodeling through protein synthesis and an upregulation of enzymes and things. So cancer cells really can't do that because when you hit cancer cells really hard with a high level of oxygen, it can actually trigger cellular apoptosis and necrosis, which you can start killing off cancer cells. They simply do not have the capacity to deal with the massive burst of oxygen-free radicals that accompany a big hit. of hyperbaric oxygen. Same thing applies with the chemotherapeutic agent. So chemotherapeutic agents, they're not selectively, you know, augmenting oxidative stress. Radiation can be targeted to the tumor, but it has a lot of off-target effects and then you get a lot of damage. Plus, that radiation,

the chemo, is also creating more mutations in the tumor that could cause the tumor to mutate in a way to become more aggressive. So where it's hyperbaric oxygen, it is a more gentle approach to increase oxygenation in the body, and then you have selective hyper-oxygenation and far greater oxidative stress in the tumor tissue for a number of different reasons that I went through. But the tumor environment is a really good environment

to apply hyperbaric oxygen because you have a lot of dead cells and a lot of free hemis. and that creates a lot of iron. So when you apply oxygen, it's almost like throwing gasoline on the fire, and then you can, to kill tumors. So it all sounds really nice in theory, and it works really well in cell model systems

and animal model systems. High oxygen, no sugar. High oxygen and no sugar. Yeah, when you couple high oxygen with very low sugar or glucose, right, like a ketogenic diet by restricting sugar, that actually can restrict something called the pentose phosphate pathway. And by restricting, you know, cellular antioxidants like glutathione, you basically impair the cancer cell's ability to protect itself while you're hitting it with high levels of

oxygen. Wow. So in theory, I mean, this is all textbook stuff that we know, you know, there's not a whole lot of motivation, though, from federal centers, organizations that, cancer research to like really further study hyperbaric oxygen. We just know that, you know, when you put certain patients and you give them hyperbaric oxygen, they do much better, you know. But we're basically using hyperbaric oxygen in the current scenario to reverse radiation necrosis. So patients that are receiving radiation, they get really bad wounds. You give them hyperbaric

oxygen. And boom, they recover really fast. Their wounds heal up. And then the cancer, you know, they have much better, you know, prognosis. Why do you think, why do you think that is? Why is so much of the, the clinical budget, clinical research, trial budget dedicated to not, why isn't it dedicated to things like hyperbaric oxygen or, or diet, such as a ketogenic diet, restricting sugar and glucose,

when clearly there's tons of, tons of research and science to back that? One of the things that I sent you in the email was one of the things I came across was like 75% I think 70 to 90% of US clinical research funding is dedicated to drugs and medical devices I think it was yeah yeah well the national institutes of health is a major funder of research right and and I think at least 50 billion dollars I think per year to clinical research and that could be drugs. And I know a small minority, not even 1% of that is going into nutrition research.

And with cancer... Which is insane. Yeah. And with cancer, you have a number of different, you know, things that are being funded. It's over two... For 2022, it's going to be over $200 billion in funding. And pretty much no funding goes into cancer prevention, right? So there's so much that we could be doing now to prevent cancer.

from being a problem in the first place. So we could prevent a lot of cancer through lifestyle interventions, like really, really, really move the needle. Like it's a huge lever to pull. So with, you know, there's not a whole lot of incentive for funding nutrition, not a whole lot of incentive for funding hyperbaric oxygen. And I think that's part of the reason. And it's just easier to prescribe a drug, you know,

treat someone with with the drug and drugs do hold a lot of promise we do drug research right yeah yeah you're you're big into pharmacology are you yeah yeah you used at least you in a pharmacology department right right uh i mean we've looked at things like people you might be familiar with like metformin for example metformin's a type two diabetes drug and when we give it to cells cancer cells and culture more cells die when we give it to animals that have you know metastatic cancer different tumors they live a little bit longer but it's it's not as much as if we apply a well-formulated ketogenic diet you know we've used something called dichloroacetate you know my colleagues do drug research with a variety of different drugs and when you compare you know research

in preclinical animal models and with the ketogenic diet and what the ketogenic diet can do in extending life and reducing tumor. It's really remarkable. So, and some drugs actually work much, much better in the context of a ketogenic diet. So there's certain metabolic drugs like, uh, uh, P.I.3 kinase inhibitors, for example, developed by Luc Cantley, I believe that the, they're largely, mostly efficacious in the context of a ketogenic diet because, well, this particular drug, there's a counter-regulatory effect, which causes an increasing insulin. And when you couple the drug with the ketogenic diet, that suppresses the hormone insulin, and then that actually makes the drug work. So a lot of the effects of the ketogenic diet is not just simply due by reducing sugar, but it has a major hormonal effect on the body, including insulin, the hormone insulin, and then insulin signaling in general.

You know, we're talking about AMP kinase and mTOR and all these go down that route if you want to, but it's hitting many downstream. pathways that the pharmaceutical companies are scrambling to develop drugs for, you know, these pathways like, like mTOR specifically. So the ketogenic diet does that naturally. It does it in a way that it's not only hitting one pathway, that it's hitting many different pathways in synergistically, if you will. So by lowering glucose, lowering insulin and insulin-related signaling and also elevating ketones. And then ketones by themselves have anti-cancer effects, anti-inflammatory effects and neuroprotective effects. So if you put a brain tumor patient onto standard of care, which includes chemo and radiation, and you put them on a ketogenic diet,

the ketogenic diet is putting metabolic stress on the tumor and making the tumor selectively vulnerable to those treatment modalities, including radiation and chemo. It helps you kill more tumor. Whereas the healthy tissues are benefiting from the elevated ketones because the ketones are actually protecting the healthy tissues from the inflammatory effects of radiation, the reactive oxygen species. So they are neuroprotective. I mean, we know that sort of from a lot of the research that we've done, right?

Right. Because we hit cells, we hit animals, we hit humans with very high levels of oxygen. And it basically causes a massive burst of oxygen-free radicals similar to radiation. But we are applying, we are doing it in the context of elevated ketones. And we typically do that with like an exogenous ketone, like a ketone ester or ketone salt formulation. So we deliver that. Yes, yes. The keto start product is the product.

The product that I use on a routine basis. And, you know, there are more powerful forms of ketones in terms of esters, but I probably wouldn't want to take them on a daily basis. But under the context of certain extreme environments, you know, you can deliver ketones in a dose-dependent manner to be neuroprotective and also to improve performance resilience. So there's a breakdown of performance under certain environments. And we think that with the correct formulation of ketones or different energy intermediates, we can preserve that performance in extreme environments. What did you say the number was, again, for clinical research in the U.S.? How many billion?

Yeah, I think, well, I'm just talking about the NIH. Just the NIH. Yeah, I mean, you have Department of Defense, NIH, many different organizations, foundations, and things like that, American Cancer Society. So for NIH, they have about 50 billion. 50 billion and you know that's that's not a whole whole when you think about right you know cancer research in general just from all the different organizations about two it's going to this year it's going to be about 200 billion dollars but you know the budget for nutrition is like less than like one percent of that less than one percent of that and the united states is is what are that here the number 68 in the world in healthy life expectancy. Yeah.

I didn't know it was that low, but, uh, I mean, yeah, it's, it's pretty low. Uh, and I'd like to just go back to like nutrition. When I talk about the NIH funded nutrition, they're really looking at like growth and development and preventing nutritional deficiencies and maybe there's a big push now for NIH to, to understand personalized diets, like how certain diets affect different, different populations. But it's not in like the, like, the, research that I'm talking about. You know what I mean? It's not like developing healthy eating to prevent or delay cancer or to increase your outcome, to improve your

outcome if you have cancer. There's just not a lot of research in that area. Although I'd like to say that the National Cancer Institute's because there's so much pressure and because there's an acknowledgement that cancer is in part a metabolic disease and probably in part a genetic disease too. There's a dynamic interplay between the two. The National Cancer Institute, they recognize that nutrition is a big lever to pull. And there's a lot of research funding going into this idea of using nutrition to improve certain drug therapies. So there's the drug therapies are still the main treatment, but, and nutrition is just really brought in to enhance. enhance the effects of certain drugs.

So that's so backwards. Well, I kind of understand it. So from the perspective of if you have a particular tumor type that you know could be responsive. And then for example, you know, a treatment has limited efficacy. And it could be a chemotherapeutic drug, could be radiation, could be immune-based therapy. Let's bring the ketogenic diet in or nutrition therapies to make that that, standard of care, which is not working, work. You know, so it's thought to be unethical to use nutrition as a standalone therapy.

So most of, uh, 10 years ago when I, I realized that the ketogenic diet had the potential to be an anti-cancer therapy for cancer, uh, therapy for cancer. I went to clinical trials.gov and I saw maybe two or three different clinical trials. If you go to clinical trials.gov right now, clinical trials.gov and type in ketogenic diet, you're going to see dozens, if not, probably well over 30, maybe 40 clinical trials with the ketogenic diet. So that's like an explosion of ketogenic diet research. And the majority of them are, very few of them are standalone therapies. Most of them are using the ketogenic diet to augment immune therapy, to augment a metabolic drug or to augment standard of care.

you know, these therapies are what really generate the revenue for cancer treatment centers. You know, you're not going to get a ketogenic diet is not going to generate revenue for, so that that's kind of, you know. But oxygen therapy could, right? Oxygen therapy could. Yeah, yeah. So it's like all the rich people, you know, you can afford those things. They're so expensive, those hyperbaric oxygen chambers for your house.

Yeah. But, you know, they do have the centers where you can go and rent one by the hour or whatever. Woon healing centers. Yeah, they're really big. And so I think cancer centers should be leveraging wound healing centers and sending people into multi-place chambers when they're undergoing their chemotherapy. There's a lot that we don't know. So every person's response, almost like to diet, you know, your individual response to hyperbaric oxygen may vary. And the dose may be different between different people, right?

So the dose, the timing, you know, the frequency, the duration, all these things need to be taken into account when, if we're talking about using hyperbaric oxygen as a treatment. So, and these are a lot of unknowns. And I suspect that's a big reason. In the world of wound healing, it's just, you know, five days a week, you know, two atmospheres, 60 minutes or whatever. It's just like this cookie cutter approach. But when you're dealing with a cancer patient who may have impaired immune system, who may have. who may have, you know, if they're really old, maybe you're pushing oxidative stress too high, like in their body and they need.

So with our protocol, that's actually why I did not do five days a week. That's why we did Monday, Wednesday, Friday. It's kind of convenient and fit in with the week. But the idea was to come in with a big hit of oxygen, really stress out the cancer cells and have one day for the body to naturally adapt and upregulate its own antioxidant systems. and then come in on Wednesday and hit it again, and then a day of recovery and Friday come in and hit it again.

And this seemed to work really good right out of the gate. So we were just like, well, let's just stick with this. And then we did try lower levels of oxygen. So we went from like 2.5 atmospheres of oxygen because a lot of people kept asking me. They have access to a soft chamber but not a hard chamber. So we went and did a mini pilot study with just 1.5 atmospheres of oxygen. And we saw trends for improved survival, but it was not statistically significant. So when people ask me, you know, does lower levels of oxygen, I have cancer and I want to use soft chamber, I have to say there's no effect.

We didn't see an effect. There was trends, but it was not statistically significant with the- Really? It was not, you know, with like eight animals or ten animals or something like that. So I had a hunch that if I was to get more funding and then we could boost the, animals to, you know, 20 or 30 animals per group that we would get the power to get statistical significance. But when people ask me if lower levels of oxygen would work, I have to say, well, we didn't

show an effect, you know, statistically significant effect. So I advocate for using a higher level of oxygen. Two atmospheres. Two atmospheres. Unless, you know, if someone has like a cancer in the lung or maybe if they have a brain cancer, then you could be more susceptible to oxygen toxicity seizures. So it's good to start low, you know, good to, and do a couple sessions low and then work up.

So the great thing about hyperbaric oxygen therapy is unlike standard of care therapy, like chemo and radiation, you come out of the other side with standard of care. You come out of the other side like a broken individual. I mean, your system shock. Yeah, your whole body, it is. It's like, patients say it's like they got ran over by a truck. They ran a marathon and then a truck ran them over at the end. I mean, they are really in bad shape.

Whereas with hyperbaric oxygen, it's like actually enhancing your own body's resilience. Like it's improving stem cells. It's like augmenting, you know, your immune system in ways to reduce inflammation. You know, it's improving your overall health. That can't be said for any standard of care chemo immune or radiation protocol. everything's, you know, it's just going to bang you up. So we are very motivated to develop a comprehensive, non-toxic, metabolic approach to treating cancer.

So that includes like nutrition and, you know, hyperbaric oxygen, of course, supplementation, but also exercise. We have not done a whole lot with exercise, but we notice that exercise can move metabolic markers in the direction that would improve outcomes. So we're going to set up experiments to do exercise. What about like anti-aging and longevity? Like what sort of effects can, like for example, my friend who just bought this oxygen tank, he wants to use it like an hour a day.

And every other day he has these people come to his house and give him, I think, like, 500 milligrams of NAD. And he also takes tons of supplements. I mean, every other day, 500 milligrams of NAD. Plus he wants to do the hyperbaric oxygen and all this stuff. Like what sort of studies has you seen? It's just like, as far as like maintaining a healthy, active lifestyle for like athletes using this kind of stuff, how does that benefit? Even for like lifting and exercise and stuff like that.

Yeah, I probably get a couple emails every week, not every day. At one point it was like every day about the longevity effects. Because the Israelis published studies showing that you can increase your telomeres, right? So, which is a marker for, for longevity and aging. So there was quite a bit of work done, as I mentioned, when you're exposed to hyperbaric oxygen, it augments your indigenous antioxidant system. So that includes like enzymes like glutathione, superoxide dismetase. These are things that your body produces to protect you from the environment from oxidative stress. And oxidative stress basically causes us to age.

So like rust oxidizes, so it ages, so our bodies oxidize from the inside out. Hyperbaric oxygen may be a way to delay that, but I'm skeptical of it. The NAD question is like an interesting one. So I have been using a supplement that's NMN and also Resveratrol. Is that the Verso stuff? Yeah, Verso. I got some of that too. Oh, do you?

Yeah. Yeah, I know the owners of the company very well. I was actually, I will, I guess I could say this, I served on federal study sections and everything where we evaluated the effects of NMN, nicotinamide, ribicide, and nicotinamide mononucleotides. And I was always very skeptical and gave like a lukewarm review to many of these grants that were, because I was not convinced that you could take it orally. and that it would end up in the cells of the brain, that the gut would essentially render it inactive. So your friend, I think, mentioned you did an NAD drip, right? Yeah, he does them every other day, yeah, 500 milligrams.

Yeah, that's a pretty, that'll get it done, 500 milligrams. So that will probably get into cells. So that's probably offering a benefit. But I am convinced that the Verso product, for one thing, And, you know, we're just friends with them, no affiliation or anything. So that's a product that I used that if when I bumped up the dose to doubling the recommended dose, which, and then I had a stint with COVID and I actually bumped it up to 12 capsules a day. And I think I. 12 capsules of that stuff?

Oh, my God. So, but I'm convinced that I bounce back really fast once I started to do that because I had not been taken it actually. And we could talk about COVID a little bit. But we were traveling and you're supposed to keep it refrigerated and I didn't bring it with me. And then we got back from traveling. And then my wife and I came down with COVID. And I noticed at when it peaked when my fever was highest, then I started taking it. And then I started improving pretty rapidly after that.

But I've talked to enough people to convince me that a large dose of NMN, the Versa product or other products, although I think Versa is probably superior to most out there. And then the IV, I've talked to quite a few people who are getting NAD drips. And they're claiming, you know, it's pretty effective as far as increasing their energy. And it's a subtle increase in energy. It's not like a caffeine hit or anything. And I noticed it when I was tracking my exercise activity in particular. I swim pretty much every day. And it gave me a second wind in swimming when I bumped up the dose to, which was like double what they're recommending on the bottle.

in the beginning I didn't notice anything but my wife noticed something which was curious to me because she never notices anything anything she does so she was telling me that it works and she stopped taking it and then she felt the decrease like she went back to normal then she started taking it again and this is

my wife doesn't BS anything so I got a little bit curious so then I took it and didn't really notice anything but then I doubled the dose and I'm obsessively track everything so I tracked my last and how I feel subjectively and objectively. I time myself and how I feel subjectively too.

And then I definitely noticed after two or three days of doubling the dose that I got like the second wind. And that was very interesting to me. During the exercise. During the exercise. Yeah. Yeah. I didn't notice it lifting weights didn't make me stronger or anything. But I noticed during aerobic physical activity in the context of pushing my body harder.

So once once the activity starts, starting, started to get hard when I usually give up or fail or have a performance decrement, that's when it was like working. That's when I subjectively felt it was working. And then that actually aligns really well with a number of people that I'm communicating with athletes and scientists and actually the data too. When you, you know, push mice or rats to a certain point, it gives them that extra little boost. And the same thing I could say with like exogenous ketones.

Like I take exogenous ketones during the day. It gives me a little like neutropic boost. I have more, you know, brain energy. And I don't really recognize the benefits when I'm lifting weights, although it may help with the recovery and adaptive processes. When I put myself in a situation aerobically, if I'm, you know, pushing beyond that typical limit, that's when I noticed that, you know, two, three, maybe four percent boost.

I know you were talking about how. how you fasted for seven days and you deadlifted like an insane amount of weight. I told you last time, after I did a, uh, the first time I did a, a five to six day fast on the fifth day, I was able to do pull-ups,

like three times the amount of pull-ups I'd normally, in my mind allowed to do like my body lets me do. Yeah. With, with, with very, very, very little,

um, work. Like it wasn't nearly as hard as it normally is, which is very strange. And then also I played basketball. basketball for two hours and I didn't have the fatigue or like the the side stitch cramp that you get when you're you know over-exerting yourself like yeah just that alone was enough to convince me that you know whatever whatever it was that I was getting from that extended fast whether it be the

ketones I thought I thought it must have been the ketones you know my my the fuel not was not glycogen um you know that's what convinced which that's what introduced me to you that's what it convince me to try the ketogenic diet and then eventually low carbs. And, you know, since then, I haven't been able to maintain a strict ketogenic diet. I've cut out a lot of carbs in my life. I used to eat pasta probably two days a week. Now I haven't eaten. I don't eat.

I just replace that with like high fat, low carb meals. I don't know. Is there, do you think there's a benefit to if somebody is not necessarily following a strict ketogenic diet, ketogenic diet every day, say somebody eats a couple plates of pasta a week, replacing those couple of plates of pasta every week over a period of a couple years with a high, fat, low carb meal. So it's not going to necessarily put them in ketosis, but it's going to cut out the amount of carbs they're consuming over a long period of time.

Do you think there's any benefits to that? Yeah, absolutely. So it's a spectrum, right? So your metabolism is a spectrum and the output would be your respiratory quotient, which is, you know, your O2 consumption and CO2 production. You know, it comes out as an equation in expired air. So as we reduce carbohydrates and when we reduce sugar and we add more fat in, we start to oxidize more fat. Our bodies are, we're omnivores. We are great in that we burn what we feed our body.

bodies. And if we can adapt our metabolism over time to be more metabolically flexible, which means, and we should do this, we should eat, we should vary our macronutrient, you know, ratios and things like that. But if we simply titrate the carbohydrates down, typical U.S. carbohydrate consumption anywhere from two, 300, maybe athletes, 400 grams a day. If we back that down to like, you know, maybe start 200, then go 100 and then drop it, then we're shifting our metabolism to burn more fat and less glucose, right? And when in regards to low-carbon ketogenic diets, the more you do it, the easier it gets and the more benefits you derive from it because you're getting more adaptive effects from it. So a scenario would be that if you go on a ketogenic diet

and follow it for a couple of months, or we did this with rats where we put them on a ketogenic diet and then we take them off the ketogenic diet and put them back on the ketogenic diet again, they make ketones much faster once we switch back to a ketogenic diet. So we call that a metabolic switch. You can hop in and out quickly. Yeah. So this metabolic switch, we noticed, though, that older rats don't have that robust metabolic switch as much. But if we do intermittent fasting is a way to increase that.

So there are different approaches you can take to get your body. I think, you know, your listeners really want to be more fat adapted, like coax their body into burning more fat, either dietary fat or fat on their body, you know, obviously. So one way to do that would be to simply restrict carbohydrates. It does not need to be ketogenic. You don't have to, like, be in a state of super low glucose, low insulin to be making ketones. So that has benefits and can be therapeutic for many different things, right? but it doesn't, you could be burning your body fat at a much higher rate just by reducing carbohydrates from, and it's relatively speaking, right?

So if you're eating 200 grams of carbs and you just drop it down to like 50 to 100 grams of carbs, you're going to be burning like twice as much fat, like literally. So your body is going to tap into its fat reserves and your dietary fat will be higher too if you shift. You know, if you drop carbs, you got to replace it with something. You could do it with protein and fat. So the more we do that, there's adaptive processes. that happen in our liver at the level of the muscle and even our brain we start transporting ketones across the blood brain barrier and then our brain starts using ketones for fuel and not only using

ketones for fuel but the brain adapts to using lower levels of glucose which means and you see this with people with with diabetes right so if someone's like diabetic and they wear a continuous glucose monitor and their glucose level is like a stays at a hundred And then through a dietary intervention or even like a drug intervention, you drop that down to like 90. That's still relatively high glucose. That should be a lot. But the relative changes, they will perceive that as hypoglycemia because their brain is used to 150 milligrams per decilator of glucose, right? But when you go on a ketogenic diet or you do intermittent fasting, that trains your brain, for lack of a better term.

I could talk mechanistically what's going on, but the brain adapts to using to being comfortable at a lower level of glucose. So I've been in situations where I'm fasting or on a ketogenic diet or even if I take exogenous ketones, that tends to lower my glucose too, where my glucose is like 52, sometimes as low as 48. And that's when I feel most lucid and have the most brain energy. Right.

Because there's various transporters associated with getting glucose, goes across membranes and that could be the blood brain barrier. And then you have the cellular membrane, which is the membrane on the neuron, you know, getting it across there. And there's a variety of different transporters with ketones. It's called the monocarboxyl gas a transporter. And these things get upregulated, which means like you have a neuron and it's got like 100, 100 little transporters, but you go on a ketogenic diet or start fasting.

And then it ramps up production of these proteins, which are your transporters are protein. They get embedded in the membranes. and then it allows your body to transport more of this energy across the membrane, and then even into the mitochondria, where there's also transports. So this adaptive process does not happen overnight, but the more you adhere to intermittent fasting protocols, carbohydrate restriction or ketogenic diet, then you upregulate ketogenic enzymes,

which are enzymes that make ketones. So you're making more of this alternative fuel. You are augmenting the production of ketogenic. olytic enzymes, which are enzymes within the mitochondria in the cell that actually allow us to generate energy from ketones. And then you're also increasing the production of the transporters. So we can get more of this fuel across. So there's a lot of adaptive things. And you talked about, you know, when you're fasting, you did more chin-ups and everything. I think a lot of things are going on there in that you basically, you basically, you, you know,

you're relieving your body of the burden of digestion, right? Digesting and your organs. That actually uses a lot of energy. So when you're fasting, you know, all that extra energy and blood can actually go to your muscles and go to your brain. And when we fast, about 24 to 36 hours into fasting, we have about a 30% increase in brain blood flow. And this is kind of like a mystery, but people are studying this. and I think it has to be attributed to, then your gastrointestinal system, your liver, your kidneys,

your organs take up a massive amount of energy and blood. And then because you're not digesting food or anything, that frees up a lot of it. Your liver actually shrinks. You know, you have less glycogen and less metabolic activity in the liver. So you have more blood in circulation available to your muscles. And the inflammatory state of your body goes down. So your inflammatory markers, your cytokines, and your chemokines go down.

And when that happens, the skeletal muscle, the actual contractile apparatus of the skeletal muscle, the calcium signaling, even at the level of the sarcoplasmic, you know, reticulum and the neuromuscular junction, you have a better, a better activation of muscle contraction from the brain to the motor neurons to the neuromuscular junction, you have a better activation. of muscle contraction from the brain to the motor neurons to the neuromuscular junction to the release of calcium in there. So you have a stronger, more efficient contraction when your body is in the state of lower inflammation. You know, you reduce the burden of having to digest food. And then you have ketones too that are in the mix.

So your body becomes a more efficient machine. So this probably, you know, your strength will probably go up in like pulling exercise, maybe in deadlist, but probably not things like bench press or, you know, which certain exercises, you have the advantage of maybe holding extra weight because you simply have, if you expand the cells, you know, with like creatine and carbs and you're holding extra glycogen, then you essentially have more cellular leverage to move more weight. So, so for example, my nutrition, fasting regimens are different depending on like what

type of workout I'm going into, you know, so that's, that needs to take into account. Yeah, that's another thing I wanted to ask you about. Obviously, you know, you, I'm sure you spend a lot of time during your day sitting at a computer doing research. Way too much. I do the same thing. 12 hours a day. So when I try my hardest, I can go on, I can go on a month-long stint of being pretty

damn close to being in ketosis. But there's so hard. many like questions. I'm trying to like form it into keep it organized. Um, when what is your specific regimen when it comes to like your everyday. I know you have different workout routines that you're going into, but for someone like you, you're a big guy, you work out a lot, but you also spend a lot of time sitting down like what and sitting at desk working not being not being active. It's different for people like you or people like myself, um, than it is for somebody who works like construction or is on their feet running around all day.

For someone who spends a lot of time at the desk, like what is your regimen, for example? Like how often do you typically eat? What does that look like? And then what type of supplements are you taking? Yeah, all good question. Well, I think sitting can be like really toxic if you're sitting all day. So I actually built the stand-up desk at home and then working a lot at home with COVID.

But I also teach. And, you know, like last week, I had to teach all week, and I'm standing behind a podium. So that's better than, you know, sitting at my desk. And my students actually bought me a stand-up desk for my office. So, yeah. So when I got tenure, they bought me that. So it kind gifted them. So I do probably more than 80% of the time, if I am at the desk, I'm standing.

And moving around from conference calls, like I walk around and do that. So depending my nutrition will vary depending upon if I want to lose weight, maintain weight, or gain weight, right? And also varies depending upon my routine. I'm talking just to my routine will depend upon the type of workout that I'm doing too. Last week, I guess for an example, I hosted Thomas DeLauer. He's got a massive YouTube page. check them out it's like 3 million followers and I knew he was coming and I knew he was going to my typical routine is you know through in academia you just you have very long hours so you know

even when I was a PhD student it was like get in there lift really warm up lift really heavy and get and get out and then I was able to build a lot of muscle just doing that and a lot of strength and size Dorian Yates and Mike Menser popularized an approach called the heavy duty approach And it was just like I followed them and would learn to warm up and do two or three major compound movements and maybe one or two accessory movements sets really and be out. So I still revert back to that today. Although last week was really challenging and it was really pushing me. I do a lot of work outside. We have a farm.

So I'm always, you know, moving hay bales and shovel and poop and just, you know, cutting logs and stuff like that. So that has kept me in shape. You're a real man. Yeah, yeah, yeah. I enjoy that. And that's part of like my routine, actually. And so yesterday I spent a good time fixing fences and cutting logs and everything. That's awesome.

So, yeah, last week was kind of fun because I was put through a workout that I typically don't. It was like maybe an hour and a half of training. And we did a wide variety of high volume from weighted dips to chins. And then we did shoulder exercises and all these accessory movements I typically don't do. And it was like freezing cold. but Thomas Dallauer is like an animal. He had like no sleep. He came in,

slept three hours, but he does intermittent fasting ketogenic diets. And he's a pretty big dude, like pretty heavily muscled. And then we did our workout, which went well. I was able to keep up with him.

And even dead lifts, you know, you know, I'm pretty strong on that exercise. But we went from that to training outside where I had a thousand pound hay bale. And the idea was to roll it across the farm, across the cowbridge,

to the other property. So we had, we took turns rolling this thing across the pasture. And, and that, that, it's like pushing the sled, but even harder because, you know, it's wet. It's like, you know, this thing, it's hard to push up hills. I mean, it totally spent, you know, totally drained every amount of ATP I had. And I really felt in that context, and we talked about it after, and we actually, you know, develop some interview content around this idea of that would have been a good scenario or good point in time to add carbohydrates because I typically don't train that way. If I was ketogenic, I could probably train my body to do an hour and hour half workout. But because my workouts are usually 30 minutes, if I extend it to an hour and hour and a half, not having carbohydrates would be detrimental, I think. but I feel like I could get a sufficient amount of stimulus within a 30-minute workout to grow muscle and to grow strength.

And just going beyond that is just like a waste of time because I'm not like a professional athlete or anything like that. Although if I was going to be, you know, a bodybuilder, competitive powerlifter, a football player, I would be doing two or three-hour workouts. And I would probably introduce some carbohydrates in and around my workout, but not much. A little bit goes a long way. But, you know, and I would probably add them intro work. out about halfway through. So, but for me, I really, I probably spend about an hour and a half.

Like, carbohydrate supplements? Yeah, like a little bit of, you know, simple sugars in the form of glucose polymers or, you know, I will, I actually just have like dark chocolate. I'll have some dark chocolate if I want a little bit of carbs. And sometimes I get into routines where like I just, I'm cutting, I'm just like moving logs all day and just like, it's like, eight hours of deadlifting, you know? Yeah. If I'm doing some fence work or something like that and just doing a lot of heavy farm work.

And then I will titrate some carbs in it. I feel it. I mean, but I like to keep my body hungry for carbs. And in the process of doing that, you're adapting your physiology to be able to perform and preserve that performance in a low carb state. And I think there's a lot of advantages to that. So your glucose is low. your insulin is low, and that allows you to tap into your fat reserves more efficiently.

So we have an endless amount of fat. Even a lean person has, you know, 20 to 30,000 calories of fat on their body, even a lean person. So we can always tap into that. Whereas, you know, if we cut carbs completely out within like 24, 36 hours, we're going to deplete our liver glycogen. But if we are fat adapted and we have good metabolic flexibility, that means that, And a good way to assess this is if you stop eating and you fast, and if the fast is extremely painful and you get a headache and you just can't perform, then you're not fat adapted. So one way to get your body more fat adapted is simply the first way to do it is to simply eat within a 12 hour window and fast in 12 hours. So start there.

And then you can push it to like a 16 hour fast and eight hours of eating. Some people go to like 20 hours of fasting, four hours of eating. If I did that, I would lose way too much weight and size and strength. So what I do personally is just I do intermittent fasting a 16-8 protocol just twice a week, if that. And that's actually enough. So 16 hours of not eating? 16 hours fasting. 16 hours of just skipping breakfast.

Like last week I may lecture twice. It's like I would just finish my lectures for the day around 2 or 3 o'clock in the afternoon. and then that would be my first meal. So, and sometimes, you know, during the day, I might have some ketone supplements or I might have, like, black coffee or something like that. Yeah. Sometimes I put MCT in it. Sometimes I don't. But basically, the most important thing is to keep insulin and glucose low, and that pushes your body to be more fat adapted.

And when we get fat adapted and we go in a situation, if we don't have any carbs or if we go into a fasting situation, the body is completely immune to. the energy crisis. So your body knows what to do, quickly liberates fat for fuel. And I think a lot of things are going on there. It's like you're increasing something called glucagon. You're stimulating your sympathetic nervous system, your catacolamines. And that's basically hits a hormone called hormone-sensitive lipase. And so basically it just like it opens the floodgates for fat to go out of your cell and to be used as energy. And some of that fat goes to the liver and through ketogenesis, you know, generates ketones, and then ketones can largely replace glucose as an energy source, which you were experiencing when you're fasting for five to seven days.

Yeah. I did. I quit on the sixth day. I wanted to go seven, but I couldn't. Yeah. Well, at that point in time, like the majority of your brain energy was coming from ketones. Like if you fasted that long. So it doesn't, it takes a while to get to that.

For me, at so, and we calculate this through something called the glucose ketone index. So you can measure glucose and in milligrams per decalator or a millimolar. So in millimolar, we're about like four to five millimolar is normal. But when you fast, you don't go to zero because we always produce glucose through gluconeogenic amino acids and the glycerol backbone of triglycerides becomes glucose and everything. So our glucose goes down but stays like low and stable at about three millimolar. And after about three days of fasting, on the first day, if you're eating, a standard diet, your ketones are like zero, right? So, but after about three days of fasting,

you're up to about three millimolar ketones. So we call that a glucose ketone index of one, right? So the level of glucose in your blood is fairly equivalent to the level of ketone in your blood. And your brain will use whatever fuels available. So you have the transporters for both. So you're using about 50% glucose and 50% ketones at about three millimolars. At three millimolars. That's That's for me and for I tracked many different people, especially athletes at about the third day, they have a glucose ketone index of about one, which means you get your brain's like a hybrid engine. You know, it can use glucose or ketones or it could use both, right? So in that particular state is very therapeutic. So a glucose ketone index of one is tremendously neuroprotective.

It's tremendously anti-seizure. you know, organizations like Johns Hopkins and Mayo Clinic, when they have kids that come in and put them on a ketogenic diet, if they can get their glucose ketone index to one, then that has remarkable seizure control above and beyond any anti-convolent that we know of. You know, that's really amazing to me. And that's what actually motivated me to like spend my career studying this. But when you were experiencing it, you probably felt lighter. You probably felt everything was kind of like smooth, you know. I was my mental acuity, my, I was so much sharper when I was thinking and talking. I could do things like this so much better.

Like no, no fatigue, no mental fatigue at all. Yeah. Yeah. I typically, like this morning I had steak and eggs for breakfast, but because I was like so active over the weekend, it was just like my energy levels were down. But typically, so as I'm transitioning more throughout the day into a more. fasted state, I can feel my body and my brain becoming more awake. So, so typically, my normal day is kind of like, you know, I don't do intermittent fasting every day. I'll eat a small keto breakfast and then fast throughout the day and then have a pretty large meal and then maybe some

activity and then like a snack at night. That's what I typically do. Sometimes I'll eat those keto bricks. Oh yeah. Like a little bit of those keto bricks. I know Robert. Just coffee. I don't know. Everything I eat that's keto is just from your Instagram page. So I just copy pretty much. everything I see you do. Yeah, shout out to Robert at keto brick. It's like one of the, so a lot of people send me keto supplements and keto products and maybe only 10, not even 20%, maybe 10% like actually are truly keto. So a keto brick is something that is like, it's a thousand calorie brick that is,

has the macronutrient ratios that are truly keto, which means you eat it. And then you are truly sustaining the, you. being in key like you could use it clinically like the product could be used like in a clinical setting oh wow it's that it's that legit okay yeah yeah i mean it fills you up it feels you i only i can only eat like a quarter of one maybe at most at one sitting with coffee they're perfect for like backpacking like hikers like hunting something like that yeah i mean yeah i eat a couple a week do you got to reorder them actually. Yeah. It's hard the hardest thing the hardest thing for me as far as like maintaining this new this nutritional state is I can fast all day long. I often I'll go a couple times

maybe one time a month I'll do a 24 hours and then I'll all I'll spend a couple days like strict keto. But other than that like when I'm just like coasting. I'll I can easily I intermittent fast most days of Monday through Friday. I try to do that at least. But then when I get home, I'll eat chips or I'll eat a cookie. Is it true that can be worse if you're in a ketogenic state from either fasting or from diet and then you splurge and eat some chips and cookies? Is that worse than just eating, just keeping carbs in your diet throughout the day? Yeah. So, I mean, I'm looking at you, looking at like your metabolic phenotype.

You're probably digesting and assimilating that. The only way, I'm, I'm kind of against, you know, processed food in general. I try to eliminate it, although, you know, I don't, I don't, my wife is pretty liberal in whatever she eats. I mean, you know, she's the same way. Yeah, cookies, candies, things like that. And she can maintain her blood glucose and insulin and within a pretty tight parameters, right? So the majority of people can't.

Majority of people have hyperinsulinia, insulin resistance. And, you know, they don't, they should not be eating these things. things. It's adding more kind of fuel to the fire. These are hyper-palatable foods that reinforce a dopaminergic pathway, among other things associated with the control of eating behavior, which is very complex. So it's reinforcing eating, the more you eat the foods, it's reinforcing that eating behavior of that, that kind of food. That's hyper-palatable. Typically high, high-fat, high-carb, high-fat, high-sugar, or high-salt content, too. So for you, I mean, you may need the calories to maintain it.

And for me, at the end of the day, sometimes I have to have like a cup or two cups of sour cream and I put some protein powder in it and some stevie or whatever just to, just to get my calorie. Yeah, I'll do sour cream, some wild blueberries and, because it's kind of like yogurt. Stevia and dark chocolate powder. And just to get my calories because I was so busy during the day.

I just didn't, you know, have my calorie needs. I'll lose weight. But I think the only way to really know if this is harming your body is to do blood work. And so I'm wearing, I talked about a continuous glucose monitor. Right. I have a Dexcom G6 on the back. And sometimes I use the Abbott Precision or the Abbott Libre device. And I use that with an app called Levels Health.

And Levels Health app is really a tool. that we are using in a registered clinical trial as a behavioral tool to more or less prevent what you just told me you're doing, which is like kind of going throughout the day. If I go through out the day, by the end of the day, I'm more hungry than if I had eaten a meal earlier the day or if I use. So that's kind of why I've, I realized that intermittent fasting was leading to more erratic eating behavior at night. And I am like, I get the munchies at night. So simply eat. eating a well-formulated ketogenic meal earlier in the day knocks my appetite down by like 30%. It doesn't go away, but I definitely am less ravenous at nighttime. And being low-carb and being keto actually helps with controlling your appetite, so your appetite's not controlling you. But what it allows me to do is that, you know, I can look at, and my phone's kind of off right now, but I could just show you,

oh, I need to access. I don't want to turn it on because it'll blow up or ever. But I can, oh, you've probably seen my Instagram where I show, you know, my glycemic response. Right. Yeah, I have seen that. In response to a Pop-Tart versus a tasty pastry, which is made by legendary foods,

which is like taste just as good or better than a Pop-Tart, right? They have like different varieties, like blueberry and cinnamon and Dutch. And then they have, and then I'll eat a regular Pop-Tart. They are two different things that actually are just as enjoyable to eat. But the Pop-Tart actually shoots my glucose to like 220 milligrams per decilator, which is like a glycemic hit. And these spikes in glucose can be pro-inflammatory. They can trigger an insulin response, quickly kick you out of ketosis and basically put you in the fat storing mode. Whereas if I, when I ate a tasty pastry,

it was almost like a flat line on the continuous glucose monitor, which means I don't have a big bolus of glucose hitting. Tasty pastry. Yeah, tasty pastry by legendary foods. So, you know, if I'm, if you have to say, if it point the finger towards me of eating one processed food, it would be tasty pastry. But it's in no way equivalent to a Pop-Tart.

And I think most importantly, from a metabolic physiology point of view, I mean, it's super friendly to, your metabolism in regards to glycemic variability. So I advocate for if you can't understand something unless you monitor it, right? If you want to manage something, you have to measure if you want to effectively manage something. So I'm a big advocate for people just knowing what your baseline is. So buy a glucose monitor.

You can get any CVS, Walgreens, Walmart, prick your finger, measure, measure your fasting blood glucose if you're over like 126 and you measure that again and you're over it twice you're type 2 diabetic and many people are borderline pre-diabetic so at the very least get you know blood work like once a year ideally three or four times a year and you know you want to measure your insulin to but glucose is like the most important biomarker for health and one way to track glucose continuously without having to prick your finger all the time is actually to get a continuous glucose monitor. Does it like go in you?

Yeah, there's an applicator and you put it on the back part of your arm here. And I mean, you could put it on your stomach and stuff too, but I like to be consistent and put it just on the, just the meaty part back of the tricep. And that's basically like a dashboard to your metabolic physiology, your glucose, right? So you get this a CVS? So the continuous glucose monitors are prescription items that are primarily used for type 1 diabetics and also in type 2 diabetics. There's a company called Levels Health that you sign up and you go through an online

application process and fill out a quick form. It might take five to 10 minutes. And then there's a third party that fulfills a prescription. and then they just send you the kit to your house. Okay. And you get a couple devices and you get a transmitter. And then you have access to the app. So that's where like the technology comes in in that within the app,

I, for example, I ate a tasty pastry and then I ate a Pop-Tart. And then I had on two different days and I had a very informative glycemic trace over the course of several hours and actually gives you a metabolic score. And then I can go into the app and then do compare. And I could just go the day before. Basically, I take a picture of it, and I write tasty pastry, and I take a picture of the Pop-Tart and just write Pop-Tart, you know, the next day. And I go into the app and I compare these two.

And it shows me, it overlays the glycemic response from Pop-Tart and the metabolic score, the rate of rise, you know, the peak rate, and the area under the curve and all that stuff is calculated. And it compares that the Tasty Pasty to the Pop-Tart. And it shows, you know, you have two dramatic, two, a very dramatic difference between, you know, two things that are just as enjoyable to eating, but two different metabolic responses. So I'm a big advocate for measuring glycemic responses to food because I thought, I thought, you know, whole-grained oats oatmeal would have a nice, flat response, but it shot me to like 200. And I thought, yeah, I thought, like, you know, eating an orange would not be to, if I ate a large orange, it would shoot me up almost 50, 60 points. So even blueberries, if I eat blueberries without protein and fat, I get like a probably a 20, 30 milligram per decilator spike. So I learned, I learned a lot of things using continuous glucose monitor.

One is that if I eat fiber before a meal, fat or fiber before eating a carbohydrate or a large amount of protein, that fiber and fat will, so eating a salad with like a lot of olive oil and a mixed greens. And then I eat a steak or a lot of protein after that. The protein could spike me up a little bit or even if I eat carbohydrates, eating that fat and fiber first will block that glycemic response. So not only like the peak glycemic response, but meaning the area under the curve. So which means the total glycemic load is reduced simply by eating fiber. So what that tells me is that I have an appropriate insulin response and the insulin is doing its job more efficiently and taking that glucose and putting it into the muscle or into the liver or wherever it needs to be. Whereas if I was to drink, you know, 24 ounces of gulf. Gatorade, that glucose is hitting the system and the body is going to dump a massive amount of

insulin. And typically what's going to happen is that, you know, the insulin gets released. It's going to stimulate de novo lipogenesis. You're going to, like, you know, glucose transporters will be overwhelmed. So you're going to get a big spike up. And then you're going to get this postprandial dip in your glucose where you're going to be super hungry and ravenous, you know, after the insulin gets, you're going to get. you're going to spike up.

You're going to dump insulin. Insulin gets released. And then you're going to get super hungry. And this is the vicious cycle. The majority of population is on right now. So they're eating carbohydrates or eating chips. They're eating things between meals. And they spike their glucose up.

And then two or three hours later, they get a post-pranial dip. And then the brain senses hypoglycemia. And that hypoglycemia is a trigger for you to go eat more carbohydrates and get your glucose up. And a lot of people don't know that, and they would not know that because they're not using continuous glucose monitor. So, I mean, I've been wearing it for years, and it's not something you necessarily have to wear for years. But if you just wear it for four weeks, it is so insightful and full of actionable information. You can change your dietary patterns to really optimize your glycemia throughout the day. And that will give you so much more energy.

It'll give you, you can perform better, you can recover better. from exercise. You can think better. So it's a very cost-effective tool. It might be a little bit pricey to buy up front, but, you know, you can, you know, it's like $200 or $300, I think. But you just, I think if you just use it for four weeks, that you get so much information out of that that it's actually pretty cheap.

Yeah. So don't fast all day and come home and eat a giant bowl of Captain Crunch. No, no, yeah. I did. There's like, there's Catalina Crunch. Which is one of the things that I've tried some of those keto cereals. They're actually not bad. Yeah.

So I think it was Magic Spoon I tried maybe. I tried my, yep. That tested okay. So I tested a lot of things. So I wear a continuous glucose monitor to vet out which truly low carb. Okay. And Magic Spoon was like pretty okay. It was surprisingly.

Although it's got like chickory root and inulin in it and that gave me gas. But and then Catalina Crunch, like two thumbs up on the taste. Pretty good. Yeah. But if I eat it dry out of the box, it was definitely shooting my glucose up. Not way less than like Captain Crunch. But, but when I, I used like a high fat almond milk or coconut milk or if I put it in sour cream and put cinnamon and ate it as a snack, then it was like no spike. So just, you know, coupling that with fats.

With fats. Yeah. It didn't spike me. One of the interesting things which I emailed you about was when I did, I believe, it was last, about almost a year ago today, I did a five-day fast. At the very end of the five-day fast, I did a blood test on myself. Came back, my LDLs were through the roof. Yeah. Remember, I set you some screenshots of it. And you said, there was a, you sent me something back where a lot of athletic or active people who are on ketogenic diets see that rate, that heightened

cholesterol. Yeah, there's a term that has been developed for that called lean mass hyper responders. So a lot of elite level athletes that are, and they don't even have to be elite level, that are following a low carb approach and getting their bodies to basically run off fat and ketones. When we look at their lipid profile, and I forget what your triglycerides were, but in the typical... I didn't get, they didn't test my triglycerides. I have right here. Well, typically what we see, you know, with athletic folks that are following more of a high-fat dietary pattern is that their triglycerides will, oh, is that ZRT?

Yeah, exactly. Yeah. Oh, your HSCRP is low, insulin's low, hemoglobin A1C is very low. HDL. I don't know what any of those mean. Your high-density lipoprotein is a little low. 33 is kind of low. relatively speaking.

I like to keep, I like to have my HDL, you know, in the 60 range. But your hemoglobin A1C, though, your HSCRP, which is your inflammatory marker, is 0.1. It's probably because I fasted. Yeah, you can't get much better than that. And then your insulin's, yeah, 3.9. So that's, that's pretty good.

The other ones are kind of cut off. But I don't see your LDL here. Oh, yeah, it wasn't. It didn't have LDL, but it had, what is the HSCRP? That's high sensitivity C reactive protein. And it's a marker. I like it. Some people, I think it's very good marker of systemic inflammation.

And I basically see that people with high HSCRP really have, you know, bad metabolic health. And as their metabolic health improves, high-sensity C-reactive protein goes down. So systemic inflammation goes down over time. And that's also people who have HSCRP, if it's high, you're more likely to get cancer. You're more likely to get, you know. Yeah. People who have cancer, I tend to see high HSCRP. So it's super good and important to have low levels of systemic inflammation.

And that's, that was very indicative of what you just showed me. So that, so even, so if you have those numbers and your LDL is high, my personal opinion, I would not be too concerned with that. So your LDL really bad. Is that like, I heard that some people claim that that's a myth that LDL is really not bad? It's very complicated and it's a nuanced discussion. Right. Above and beyond here. But my, uh, my short answer is that if your, if your glycemia levels are good,

insulin level is good, inflammation's down. Ideally, you want your HDL a little bit higher than that, but it's still kind of okay. And your triglycerides are low. Two, having a high HDL, I would not be concerned, especially, you know, if your blood pressure is good and you're healthy. So we do not know what an elevated LDL means in the context of a low carb diet or in the context of this extended fast. So I don't think my every doctor will tell you that's bad and you do something about it and you should probably be on a statin But we the science has not the science has not Doesn't have any data really on what healthy LDL levels should be in the context of like a fast like you did or

In the context of a protracted or extended like low carb diet like we just don't have that data yet But if your other if your triglycerides were elevated and and your HDL were elevated, I would be concerned. Or if your hemoglobin A1C was like 6.5, but you're like 4.1. That's like super low. So what that tells me, looking at your numbers. Are those all that considered triglycerides? So your triglycerides were not, your triglycerides should have been tested,

but I didn't see them on there. But basically, just by looking at your insulin and your glucose and your other markers, what that tells me is that your body was in a very high fat oxidation. state your glucose was low and in the context of an elevated fat metabolism you're going to need more lipoprotein you're going to need more and that's LDL is not cholesterol but it carries cholesterol so low density lipoprotein carries not only cholesterol it carries phospholipidids it carries triglycerides it carries other fats so we need more of that protein uh when we're we are preferentially, you know, using more fat for fuel because that's a transport system for fat,

for phospholipids, for other molecules. So we need more carrying molecules in circulation. And, yeah, if all your other biomarkers are okay, I would not be too concerned. Although, to follow up, the only way to really get insight into that is to do what's called an NMR lipid profile, which basically measures like your LDLP or your, your, your APOB, your LLP, L, P, little A, you know, these are things, again, kind of beyond the discussion here. But if that, if your LDL is persistently elevated across a couple blood draws, and your triglycerides are a little bit high, too, and your HDL is a little bit low, so HDL high is good, HDL low is bad. Right. You may, you may want to adjust your diet a little bit, which I've done.

Yeah. So but I wouldn't I mean those numbers are great Especially like after a fast I would expect that And it's also it's also pretty similar to mine I didn't see what your other what your I was trying to find it I was taking me forever yeah yeah on the laptop Going back to going back to going back I want to talk about the the NMN and what was the The Verso product is NMN and resveratrol

Resveritrol which produces naturally NAD right Well it hits the Sertuans, yeah, which is kind of like, and P-P-A-R. So essentially what it does is it's elevating NAD. So as we age, my, so I'm taking Verso, so my NAD levels maybe a little bit higher. So if I was not taking Verso product, my level of NAD would probably be half of what it was when I was like 17 or 18 years old. So as we age, we have a correspondingly progressive decrease in NAD levels, which is sort of like this energy intermediate that's really important for cellular energy production, you know, signaling molecules. So the NMN or nicotinamide riboside or nicotinamide mononucleotide, which is found in the VERSo product with resveratrol is hitting.

cert 1 receptor and associated pathways, which is really helping the body. The way I think about it is it's coupling mitochondrial activity and mitochondrial health with the nucleus. So there's cross talk between the mitochondria, which are the energy producing organelles of the cell and the nucleus. And there's like this retrograde response where there's cross talk. And essentially, and there's a lot of activity that's driven by NAD, cellular, you know, respiration. So the NAD supplement is sort of restoring the co-factors necessary to make ATP, but I think about it mostly from a signaling perspective as coupling the mitochondria to the nucleus and producing an appropriate. appropriate response in regards to generating the bioelectric or the bio energetic state of the

cell. So that's that's the couple. And my criticism of NMN and R was that when you take it orally, it's not getting into the cells. But I think the data is to the point now, especially if you take a large enough dose, that it is getting to the cells. And the dosage that we need, the human studies really are not there yet. And I was a little bit hesitant taking it, although anecdotally, if I take a large dose, I do feel it.

And I've not taken IV NAD yet. But the feedback from people that I respect suggest that it's pretty effective. Yeah, my friend who I was telling you about who's been doing it every other day, he's in his late 50s. And he says he doesn't really notice much of a difference. But the first time I did it, I felt like I could jump over the moon. Like I had like an insane energy boost that I haven't, I've never experienced. After that, it wasn't so bad. One time I did it, I felt like I was going to throw up for four hours afterwards.

I know when you're doing it, it's extremely stressful and painful on your body. Like you feel like it's, you feel like you feel like the flu while you're doing it. But after, I think it was the third time. I did it afterwards, I felt like I was sick for a couple hours, which was really weird. I didn't have the energy spike. I don't know if that had to do with like the needle placement. If they messed up, you know, messed it up when they put the needle in my vein or what. Was there anything else in the drip like a scorpic acid?

Like vitamin C? Yeah. Myers Cocktail. Yep. They did the NAD. Okay. So you were experiencing that sort of like coldness that you feel and the cringe. sometimes there's different effects you may feel.

Also, you have to acknowledge that ascorbic acid is a glucose antagonist. So vitamin C, which is vitamin C. So vitamin C and glucose use the same transporter. So when you get a big dose of vitamin C, a big dose IV would be anywhere from 20 grams. So, you know, some clinics use like 100 grams of IV vitamin C. your body goes into a most reactive hypoglycemia because the same channel, the glucose transporters that transport glucose also transport vitamin C, and you're blocking that.

And so there's a wide variety of effects you could feel depending upon if you went into it fasted or if you had a meal or something. And it probably had the pee like crazy too, like right after. Oh, yeah. No, the first time I did, I did it fasted. I felt great. So the time I got sick, I ate an egg McMuffin before. Uh-huh.

Okay. Yeah. Yeah. So that could factor into that. Yeah. It's probably, you're probably dumping a lot of insulin, too. And maybe you have, like, an effect after that. So very interesting.

So I think there's good science emerging from NAD. I'm of the opinion. Let's try to increase NAD levels naturally and sustain it naturally. So ketogenic diets. There are some people in the field of basic science research and clinical research that feel that the therapeutic effects of the ketogenic diet on the brain and on the body are due to a boost in NAD, NAD to NAD ratio. So there's a whole field of people kind of studying that fasting will increase NAD levels and exercise increase NAD levels. So if you do a low-carb ketogenic diet with intermittent fasting and exercise, you're basically doing like everything you're. could do to boost your NAD levels. So I don't think you have to do the IV route. I think you can get

the benefits and it's much easier, right, to take a supplement like Verso. Yeah. Yeah. And it's interesting that it helped you with COVID too. You know, I didn't expect. I think it was from like an energetic point of view. Like I came down. I had very mild symptoms for about two or three days. And then I got a fever of about 103.7. And I remember I was working all day during this, having to do interviews and stuff with the school. And although it was virtual, I wasn't like spreading my germs around. But it was that day that I actually got back on with DeVerso product again.

And I was mega dosing. I was taking 12 caps. And I turned the corner real quick. Like the next day I woke up, I like sprung out of bed. I was ready, you know, right at work. I was just like I had a lot of energy, but I could still still feel. that my immune system was in a hyper immune surveillance point of view. My glands were very swollen, but throughout the course of the day, by the end of the day,

my glands had went down and I was just left with like, you know, this tickle in the back of your throat. So for me, I don't know what version I had. I suspect I might have had the Delta variant, but maybe I had the Omicron. It started as just like razor blades in my throat. And then I had the fever right around that time or whatever. But it was really bad for two days and then just kind of lingered for a week or two after. Whereas my wife, we obviously got the same thing because it happened like the early symptoms started at the exact same time. And we both had the same fever within a, you know, one or two.

But her symptoms were muscle pain and bone pain. And actually, her symptoms were a little bit less than mine. But we both recovered pretty quick. And you're vaccinated? Uh, you don't want to talk about that? Well, you know, I am, I am because of the work I do and, you know, I chose to, to get vaccinated. So I'll, I'll say that, but I am in touch with a number of people who I was within a circle, like a family circle and friends and everything. They all got the same variant that I got, because we all got sick around the same time.

Oh, you guys were all together. Okay. Yeah, and I'm not. I mean, my wife is part of this bigger group. and it was kind of interesting in that it did not seem to make a difference vaccinated or not, you know. Between you and your wife? Her symptoms were less than yours. Yeah, her symptoms were, well, I'm not going to say if she's vaccinated or not, but I'll say that we were amongst her. She included a number of different people. And actually, the people that were not vaccinated probably had a little or no symptoms.

A couple of them, you know, didn't get infected at all. We had a big family get-togethers and stuff. Right. traveled back. Right. And then got on the phone and it was like realized everybody was sick. So I got a head count of like who's sick? What are their symptoms?

And I went through everything. Yeah. And there was a couple people among family and friends that were unvaccinated. They didn't even get it. But all their family members got it. So I think the bottom line is that I don't think that the whole point of vaccines was to decrease the length of the, you know, the pandemic. And I don't think that happened.

Right. I mean, just look at the scenario. Right. No. Now you have to get your fourth. fifth one. Yeah, yeah. And whether that, I don't think the, the protracted nature of the pandemic is due to the unvaccinated. I think we can reliably say that at this point in time. So, but I mean, I think there is something to the idea, especially if you're older and metabolic

health, if you have type two diabetes, if you're obese, if you're older, I'm all for getting vaccinated, then it becomes questionable if you are younger, if you're kids, like, you know, that's a whole other, I don't even choose to weigh in on that because it's so polarized that, you know, but I have my own opinions, but I do feel that, you know, I encouraged, you know, my family members who are, you know, older in their 70s and 80s and stuff. That might be good to get vaccinated, but, but who knows at this point in time. I just don't think it, it definitely didn't help me. As far as, I felt like I had no protection.

Yeah. You know, after being vaccinated. What did you think of all the supplements that Joe Rogan said he took when he got, because they were shitting all over him, all over the news and everything, saying that, you know, he was taking all this ridiculous stuff, like deworm, horse dewormer and all that stuff. But, you know, he took a lot of stuff. Yeah. Well, he took monoclon on antibodies.

And NAD, right. Oh, yeah, yeah, monoclon on antibodies. I took NAD. So I'm of the opinion. So I take, you know, I take examines. Zinc. I take quercidin. I actually have prescription vitamin D that I had on hand that I took for that. Prescription vitamin D. Yeah, it's actually prescription of vitamin D2. So I'll take D2 and D3, quercidin, zinc, vitamin C, a couple other things here and there. Like, I mean, for lifting, I take creatine monohydrate, acetyl-carnatine, I think is really good. If you're on a ketogenic diet, your body gets depleted in

carnitine because carnitine transports is a part of the fatty acid transporter. So we tend to deplete it just because we're burning so much fat. So I do that. And then I took a lysine, which an amino acid kind of can boost your immune system. And then exogenous ketones. So I think all of that and omega-3 fatty acids, I think are good too. So that's, you know, I tell people, I don't really take supplements, but I guess I just mentioned quite a lot of vitamins.

But it's all, you know, I wake up in the morning and I set all the powders out. I buy pretty much everything, like bulk powders, a lot of things, except, you know, of course, vitamin D is not or zinc. And then I scoop it on, just take it in the morning. And then I'll put another in a shaker bottle, some of the powders, and I'll drink that like midday before dinner or something. But I do think that there's a case for supplements. Ivermectins a little bit. I think there is some benefit. It needs to be studied more.

I mean, we have, we have cows, we have animals, we have tons of it on the farm. I didn't, I didn't dig into the, uh, that my veterinary stash of... It's funny that it's in the heartworm stuff that you give dogs, right? It's like, if you read the ingredients, it's actually in there. Yeah, yep, yep. It's in, you know, right down the tractor supply, I think they're, like, sold out of it. I do think there's a case to be made.

I think we just need to study it a little bit further, right? As, you know, hydroxy-quinole and, like the quinine derivatives, too, I think. we need to look at them. Well, it's funny. The crazy, weird thing about it is the vaccine's supposed to be for prevention. And this other stuff that people are talking about is for treatment. Like treatment of it. Like, once you already have it, like, what's the best way to treat it?

Yep. You know, and people at hospitals say, wait until you need to be on a restaurant, until you can't breathe. And then you show up. Yeah, yeah. So my hunch is that in the very early case, maybe for, as a prophylactic measure, Ivermectin could potentially be useful for some. people who are at high risk. This is what, this is just kind of, I'm just speculating here.

And also potentially good to have on hand at the first sign of maybe getting it. So Ivermectin. But I think the science just needs to catch up and support that. There's some science, but it's just not the large clinical trials that we need. And the reason for that not being funded is sort of beyond the scope of this. Yeah, every time I think I have it or I think I'm getting something or I feel something in my throat, I just stop eating for 24 hours. That's what I just do.

Or I go in the sauna. I don't know if the sauna helps. Maybe that's stupid, but I go in the sauna. I sit in the sauna and I stop eating. Yeah, actually, that's two good points. So when you stop eating, then your body has less to deal with, right? So when we're eating, that's a big hit to our immune system because half of our immune system, more than half is in our gut.

So a lot of our immune cells and immune system function is dealing with the food that we're eating to neutralize. because every time we eat, you know, if we eat a salad, if we eat a meal, there's a lot of toxic things that need to be neutralized. This is part of, you know, digestion. And not having to deal with that liberates the immune system is kind of like, you know, a bunch of little soldiers, right? So it liberates a much bigger army for immune surveillance. And we can deal with viruses that are attacking us. And the sauna is kind of interesting because we know heat will kill COVID.

Heat kills a lot of different viruses. So if you get into a sauna, one thing that we did. I kind of, I finally, we have a, we have an old spa jacuzzi thing at our house. It's a big concrete old thing. And I fired it up after a couple years. I finally got a heater for it. And I tinkered with it so I can push it beyond what it's supposed to, right? So I can go to basically where it's boiling.

So I get it under certain conditions. You know, I can get it above like what's considered like the safe limit. And I did. I heated it up to as much as possible and got in that thing. And I think that really helped me recover. I think, you know, that's why we produce a fever. You know, high, just boosting your body temperature a couple degrees makes you, has an antiviral effect.

It could decrease viral shedding. If we're in the process of viral replication, it can knock that down. And so I think that was smart to do what you're doing, you know, going into the sauna and not, you don't want to be pushing your body really hard with exercise because that could compromise your immune system. Right. And actually, you feed. the fire, but fasting and sauna are two good approaches. Have you done, is there any studies that show the benefits of sauna combined with, like,

ketogenic diet and, and cold, even like sauna, people going into the sauna and then going in really cold water? Yeah. Like, I'll do that sometimes. I'll get in the sauna and I'll come right out and I'll jump in my pool. Like right now, it's 65 in my pool. Or no, I'm sorry, 55 in my pool. Yeah, yeah.

Same here. I actually turned off our pool heater. And then I'll use a sauna. and jump in. Yeah. Now after. Yeah. So that's pretty cool.

We had ice. You know, we're in Florida now. But yeah, we had ice over, like half inch of ice over our cow watering stations and stuff. So, yeah, I'm a big advocate of that, you know, cold therapy, sauna. So you're asking about ketogenic diet. I think the ketogenic diet will enhance the adaptive responses associated with sauna. And I think, like a lot of scenarios, so we study therapeutic, we study the ketogenic diet and then therapeutic ketosis induced with exogenous ketones. We study that too in the context of extreme environments and have seen that the body is much more resilient and adaptable when it's in a state of ketosis.

Okay. And the reasons for that are reasons, you know, that we are investigating. but I could probably come up with speculation as to why that's happening, but we're still researching that. Cool. Well, Dom, thank you for doing this. That's two hours. Wow. Where can the people listening and watching find more of your work, your website, everything that you're doing?

Yeah, well, thanks for having me on. Give me this platform to speak. Ketonutrition.org. So ketonutrition.org. We have a blog there. We're pretty active on that. We posted a blog this morning on bipolar, disorder actually in ketosis. So we are very interested in actually advancing areas of science that are

underfunded. And one area is actually metabolic psychiatry. So we are going to kind of have a meeting, a separate meeting at the metabolic health summit. So if people are interested in attending an event where they have access to scientists, clinicians, and entrepreneurs, scrambling to the space and influencers, too, will be there in Santa Barbara in the first week in May. I encourage you to go to Metabolic Health Summit. So we bring everybody together to talk about many of the different topics that we're discussing today. And Noverso will be there too. Actually.

I've got to order some more of that stuff. Yeah. So ketonutrition.org, go to Metabolic Summit.com and get more information about speakers. We have speakers from Harvard and Yale and Stanford, speaking on many topics that we hit today, including basically we break it up into brain health and cancer, and then we have metabolic optimization. And then we have quite a few entrepreneurs who will be speaking on the space about the different technologies emerging that are helping this community,

whether it be ketone supplements or wearable devices. There's going to be a lot of interest in attendees there for that. Awesome. Well, thanks again, Dom. I very much appreciate it, and I'll link the stuff in the show notes below. Appreciate it. Thanks, Danny. Goodbye, World.