Dhru Purohit Show - Killing and Starving Cancer Cells Using the Power of Ketogenic Diets, Metabolic Therapies, and Hyperbaric Oxygen Combined with Standard of Care with Dominic D'Agostino, Ph.D.

Episode Date: April 15, 2024

This episode is brought to you by Cozy Earth, Maui Nui, and Lumebox. We’ve heard about Dr. Thomas Seyfried’s groundbreaking research and approach to cancer as a disease of metabolic dysfunction. Today’s guest was inspired by Dr. Seyfried’s metabolic approach and conducted his own research on brain cancer cells using ketone-based metabolic therapy and hyperbaric oxygen. His findings were mind-blowing! Today on The Dhru Purohit Podcast, Dhru sits down with Dr. Dominic D’Agostino to discuss his extensive research on brain cancer cells placed in ketosis and under the pressure of hyperbaric oxygen. Dr. D’Agostino shares why his findings provide further insight into the idea that cancer cell growth can be metabolically managed. He also discusses how exercise and a low-carbohydrate diet can be used as metabolic therapies to reduce cancer risk. Dr. D’Agostino shares the critical tests we should focus on to assess our metabolic health and the essential supplements that can support ketosis.  Dr. Dominic D’Agostino is an Assistant Professor at the University of South Florida College Of Medicine, Molecular Pharmacology & Physiology, where he develops and tests metabolic therapies, including alternative energy substrates and ketogenic agents for neurological disorders, cancer, and wound healing. While studying the effects of gasses on the brains of Navy Seal divers, he developed an approach for metabolically starving cancer cells through diet and compressed oxygen, replacing chemotherapy, surgery, or radiation.   In this episode, Dhru and Dr. D’Agostino dive into (audio version / Apple Subscriber version): The most innovative approaches to cancer (00:00:11 / 00:00:11)  The metabolic approach to cancer (1:30/1:30) Using the hyperbaric approach in cancer patients (13:00/ 9:03) The results of Dr. A’gostino’s studies on mice (17:00 / 13:50) How this research translates to patients (22:00 / 18:05) Why a ketogenic diet can be therapeutic (37:00 / 32:04) The role of exercise in cancer prevention (53:00 / 46:35) What lifestyle factors should we be doubling down on for prevention (55:00 / 50:14) Dr. D’Agostino’s thoughts on a low carbohydrate diet (1:01:00 / 56:30) The therapeutic benefits of ketosis (1:11:00 / 1:06:40) Supplements that can support ketosis (1:19:00 / 1:12:43) How to measure for ketosis (1:24:00 / 1:18:30) Checking the status of your metabolic health (1:26:00 / 1:21:30) Where to find community (1:34:00 / 1:28:16) Also mentioned in this episode: Keto Start Donate to the University of Florida (Metabolic Therapy and Cancer Research #250244) Levels  To learn more about Dr. D’Agostino, follow him on Instagram, Twitter, or his website.  Right now, get 40% off your Cozy Earth sheets. Just head over to cozyearth.com and use code DHRUP. Right now, Maui Nui Venison is offering my community 20% off your first purchase. Just go to mauinuivenison.com/DHRU or enter the code D-H-R-U at check out to get 20% off and up your high-quality protein today. Lumebox is offering my community $260 off their FDA-registered portable Red Light device! That's over 40% off! Go to thelumebox.com/dhru and get your Red Light device.  Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Di Agostino, welcome. I'd love to start high level, if that's okay with you. When it comes to an integrative and innovative approach to cancer, what are some of the most promising areas of research that you wouldn't mind sharing with our audience today? Yeah, well, I think the field of ketone metabolic therapy is advancing really, really fast. And I'm a bit biased because that's kind of the wheelhouse of our lab. But this idea that we are, really delved into you right now is using nutrition and using a toolbox of metabolic-based therapies to further enhance the standard of care therapies. So that could be, you know, chemo, radiation, and in particular, immune-based therapies.

There's a really strong rationale for the idea that nutrition plays a powerful role in altering our metabolic physiology. And if we change our metabolic physiology, our glucose levels, insulin hormone levels, and also just our brain, too, functions off glucose and transitioning to more of a fatty acid and ketone metabolism has profound restorative healing effects, especially in the context of brain cancer. And that's what we've really focused our lab on. Yeah, let's talk a little bit more about your work in that space. Talk about some of the groundbreaking things that you guys have been able to show in your clinic that have contributed to this idea of a metabolic approach to cancer as an adjunct approach to standard of care.

Yeah, well, I'd like to kind of take a step back. And most of the things that we do in our lab are basic science research. And it was Tom Seiford that inspired me back in 2008 or nine when I reached out to him and he had one of his first articles on cancer as a metabolic disease. And I was not studying cancer at the time, but I was trained in physiology and neuroscience. And he was also studying epilepsy. So I got turned on to his work there. And we made the observation that in developing some unique technologies through the Department of Defense, we had unique microscopes that could image mitochondria under graded levels of pressure and oxygen. And I was validating and testing a new system that I built as a postdoctoral fellow.

And we were testing a range of different cells, muscle cells, neurons, human dermal fiberblast. And then we had a brain cancer cell line. And we observed that it was striking. The metabolism was distinctly different in these cancer cell lines and the mitochondrial function, the mitochondrial number. And in particular, what really caught my attention was as we graded, increased the the level of oxygen in a graded way, we saw a proportional increase in superoxide anion, which is a reactive oxygen species that was exponentially higher than in healthy cells.

And then as I continued the experiment and giving cancer cells high levels of oxygen, I saw the mitochondria disappearing. So they were like literally like blowing up in the cell because of the oxidative stress. No one ever saw this before because no one had a laser scan. and confocal or an atomic force microscope inside a hyperbaric chamber. So it was like a unique observation. And I didn't know what it meant, but I reached out to people at the Moffat Cancer Center. And then I reached out to Thomas Seyfried, Dr. Adrian Sheck, she was at the Barronorological Institute. And then I was made aware of this idea of the Warburg effect, which is damaged respiration,

leads to compensatory fermentation. And the Warburg effect is essentially the phenotype of aggressive cancer cells. That's how they. grow and proliferate through kind of leveraging the Warburg effect to enhance glycolysis, which could be up to 100, 200 times higher in cancer cells. And it gave us this idea that this could be exploited relatively easily, and it was very translatable if we were to implement a ketogenic diet, especially in patients that had brain tumors, because they're already having seizures and an approved application of the ketogenic diet was for seizure disorders. So that set these observations in cells and in mitochondria underneath

the microscope let us down a trajectory of developing different animal model systems and cell-based systems and ultimately moving to collaborate with, you know, like the Moffat Cancer Center and then clinicians there to really advance this idea of ketone metabolic therapy. But I would say the whole idea was really fired up by Thomas Seyfried. And Adrian Schack, too, was doing research at the time on this. I would love to repeat it back to you just to make sure that I understand the sort of steps that were involved in it. Because it's pretty mind-blowing. And I've heard this story from a few different people.

And Thomas Seafried talked a little bit about it when he was talking about hyperbaric oxygen. And I've heard a lot of podcasts that you've been on. But essentially, the government hired you. I mean, the government basically gave you a research grant. to look at this sort of unique situation that was happening to divers, right, like divers, and you were using a hyperbaric oxygen chamber to like recreate sort of the atmosphere of when people are diving to see why is that these divers end up having this sort of side effect that comes with when they're using a particular type of apparatus to minimize the amount

of air bubbles so they can maintain secrecy in the water. And so in studying that, you had a, is it an electron microscope or like a high-powered microscope that was there that you were using? It was, so it was called an atomic force microscope, which actually gives you the scanning resolution of an electron microscope, but you could image living tissues within. You could get atomic resolution, hence the name, atomic force microscope. So I was one of the few people who adapted this technology for use in biological preparation. it advanced the field of nanotechnology, so because it's scanning resolution. And then I took it this technology and I put it inside a hyperbaric chamber.

And that essentially became my postdoctoral fellowship project, which ended up being like three or four years. And I didn't get any publications because I had to build the instrument to actually do the experiment. So after I built the instrument, I had to do the fluid gas, electrical penetrations, and then test it with different cells. And then I was like putting all different types of cells in there. And I wanted to get a methods paper out. And I put cancer cells in there and just saw this remarkable effect of oxygen

killing cancer cells. And I didn't know what it meant because, you know, I was a cell biologist, physiologist, neuroscience, but I didn't know enough about cancer as to why the oxygen was toxic. And then no one, people have tried hypoxia with tumors, but no one, I knew for sure that no one had tried hyperbaric oxygen because, you know, nobody researches, you know, hyperbaric oxygen with a microscope. So that actually got me, I'm very curious to ask a lot of questions. So I reached out to the literally the best people in the field like NIH NCI sponsored, you know, cancer biologists and asked them like, what is going on here? And that actually was the

motivation behind what became our cancer research project. Yeah. And actually as you mentioned, you, you kind of got connected to Thomas Safreid, who's been on this podcast before. We've had some individuals that have also sort of implemented his protocol as an N of one case study that was recently on the podcast with the Hippocrates Research Foundation. But just to kind of continue the story and make sure that everybody's following along with the connecting of the dots, you know, you were putting essentially live tissue in the hyperbaric chamber, right, and looking at it this with this atomic microscope. And in that process, you saw exactly what you mentioned, which is that hyperbaric. And again, just so everybody's aware, this is a

hard chamber hyperbaric right we're not talking about like the soft chamber that is at like a lot of biohacking sort of places not that there may not be some benefits to that but we're talking about you know medical grade sort of diver grade um hard chamber machine that often costs like you know a hundred or two hundred thousand dollars is my guess probably at least yeah in that process there you ended up in a position where you were noticing this effect to cancer cells and reaching out to different folks, the question was, why is this happening? What's going on and does it mean something? Right. So somebody from the outside might look at it and say, wow, you're killing cancer cells. You're having literally the mitochondria and then explode through hyperbaric,

but why can't we just do that in human beings who are alive and treat cancer that way? Can you explain that to the audience? Yeah. Well, I mean, these are observations in cells and right, like cancer cells kind of transform and they kind of mutate into different activity when you take a cell out of a tumor one one tumor cell line was u80 u87 glialblastoma cells and i kind of looked back and it was from a 44 year old patient and it made me think like it just made me ask questions as to you know has anybody tried this before so what i was seeing in the microscope was very robust and but i was reading tom safford's work and And, you know, structure, number, and function of mitochondria are dramatically altered in cancer cells.

But what I was looking at was these cells had tons of mitochondria. That was, and they looked normal with the resolution power that I had, which kind of focal microscopy at about 200 nanometers, like, you know, resolution. So they're a little bit fuzzy. But then, you know, we would do the AFM in a fixed preparation. and they seem to be kind of normal. But what was abnormal was that when you feed them oxygen, then they become abnormal in the sense that they produce a massive amount of oxygen, oxidative stress that could kill the, well, could disrupt and actually cause the mitochondria

to disappear. And that was rupturing their membranes from the oxidative stress. And then the cell would disappear too when I would record from it. And I knew that basically all cancer therapies were oxidative stress therapies. So most chemotherapy regimens are kill the cancer cells through an oxidative stress mechanism. And radiation also kills cancer cells, not by damaging the DNA, but by increasing oxygen-free radicals to then kill the cancer cells. So you have to realize that I was not in a clinic. I'm a basic science researcher, but I'm now.

reaching out to people who are basic cancer, you know, researchers, oncologists and also neuro-oncologists to see if this is something that has been tried before or could be tried. And I did know that hyperbaric oxygen therapy was an FDA-approved application for 14 different applications and one was radiation necrosis. So I went into the literature and there seemed to be better outcomes in people who had gone through radiation and was using hyperbaric oxygen to enhance their wounds. the wound healing process, and these people had better outcomes. And then I went to several meetings, including the undersea and hyperbaric society meetings,

where they had cancer patients that were just like almost going into remission and just like no evidence of disease. You know, but they would do the standard of care, then hyperbaric and then be followed after. But these were just case reports. I didn't really know what it meant. But I was in a position. I had a PhD student joined the lab now Dr. Angela Poff. And, you know, cancer was very personal to her. And it was her that was telling me, hey, I want to do this project.

I don't want to do CNS oxygen toxicity, which was a Navy SEAL problem, right? So that, so having a seizure, what happens when you use a closed circuit rebreather, a limitation for Navy SEAL divers is CNS oxygen toxicity seizures. And it's also a limitation of hyperbaric oxygen therapy, meaning that you can only go to like three atmospheres. If you go above that, you have a seizure. So, and basically what we're showing is that therapeutic ketosis, it could be achieved with fasting, ketogenic diet, or what we focused on was development and testing of ketone supplementation

to make hyperbaric oxygen more safe and more effective. So I'm giving you a long-winded answer, but we went into the direction of using therapeutic ketosis coupled with hyperbaric oxygen in the most aggressive model. of metastatic cancer that we could find. And that was the VMM3 model of metastatic cancer. That Thomas Saffert said, you know, no one had cured this model of cancer yet. And then if you could cure this particular model of cancer, you would be very much on the right track to curing this disease or managing this disease.

So that lit a fire under my butt. And I didn't have any funding to do this. But we, you know, through industry partnerships and foundations and some other stringing together bits and pieces of funding. We got the project underway in 2010, I guess the initial studies. Amazing. And what did you find? What did you find inside of those studies? Yeah. So the first study was just simply using hyperbaric oxygen. And I still believe, a lot of people ask me like what protocol to use. And I still believe that there should be a breakday between, especially if you're using higher pressure of oxygen,

the three days per week, like Monday, Wednesday, Friday. Logistically, it was easier to do it that way, too, I guess, so you didn't have to give it every day. But hyperbaric oxygen therapy, Monday, Wednesday, Friday, 90 minutes, 2.5 atmospheres. And we had basically an animal chamber where we would put mice inside this chamber. And mice, we had groups of mice that were on a standard diet, and groups of mice that were on like two different forms of a ketogenic diet. One was commercially available.

And one, we more or less engineered ourselves. And we started running the experiments. And a couple days into it, the mice started dropping out in the standard diet group, meaning that the tumors were growing fast and the tumor burden was killing them. And as time went on, we got to the point where like almost all the mice were dead in the standard diet group. And we had like not even one drop out yet, I think, in the ketogenic diet group or one was just starting to drop out. And it, you know, it really excited me to where I would get into the lab really early just to check on the mice to see what was going on and which ones were dropping out. And that was our first study.

So hyperbaric oxygen coupled with ketogenic diet therapy significantly increased survival in the VMM-M3 model of metastatic cancer. And then we did a study where we just did a standard diet and we just added ketone supplementation to a standard diet to put them into therapeutic ketosis just to see if ketosis alone. And we got some pretty remarkable effects at that too where we would even grow these brain cancer cells under normal levels of glucose, even high glucose, like 25 millimolar of glucose, which is really high. And it had a, it suppressed cancer growth and proliferation. And it also increased the amount of dead cells that we saw, just simply adding ketones to the media.

So that was, we published that in the International Journal of Cancer. And then the third publication we got was ketogenic diet, a modified ketogenic diet that was supplemented with exogenous ketones. And then we coupled that with hyperbaric oxygen. So we had like a supercharged ketogenic diet. And this like further decreases glucose, it elevates ketones to get to what's in a glucose ketone index, like a more favorable. And we can talk, Tom, see if you might have talked about what that is. And then we did the same hyperbaric oxygen protocol. And then we got even better results. So,

we did like these three papers in about a year and a half to two years. And that really, you know, that was, that was very exciting to us. And, you know, it was kind of validating this idea that I was very skeptical about that you could metabolically manage cancer in a way to increase survival. So we did not, and no one to my knowledge has cured the VMM3 model of metastatic cancer, but we got better results than what you could achieve, for example, with like chemotherapy or different like standard of care therapies. So it's been a struggle to keep this research going just because our funding is so limited. and but we're constantly like I'm working on grants now we're submitting grants all the time but and we're going

high we're reaching for NIH which is hard to get you know federal funding for these types of projects you are one of many individuals as you mentioned that are now starting to pay attention to this larger area of metabolic approach to cancer therapies as especially like an adjacent component so going back to our original question, what is some of the most, you know, when it comes to integrative and innovative approaches to cancer, what are the most promising areas of research? What of what you've mentioned are things that you've seen, you know, your colleagues or people that are in the space applying at the level of, you know, human beings, right? You've mentioned that your work and research is there with mice. What have you seen on a landscape there of people, whether it's

that are trying it on their own, finding an open-minded or integrative oncology team, or certain other research studies that might be emerging. Who's doing this when it comes to humans? Well, a lot of patients are doing it, and they're emailing me. So I'm getting a lot of emails, and many, they're in a situation where they kind of have to be on their own, right? like the standard of care, the standard of care happens to you, right? Metabolic, ketone metabolic therapy is something that you essentially do. And we're not saying that a ketogenic diet or ketone metabolic therapy is going to cure cancer.

But what it does is it metabolically manages cancer growth and reduces cancer growth just by hitting a wide variety of mechanisms that are, you know, that pharmaceutical companies are trying to tarmacosurricular companies are trying to, target, right? Many of these mechanisms are amenable to pharmacological manipulation, for example, glycolytic inhibitors, 2-deoxy glucose, lonidamine, 3-promopyrvate. You probably heard about this drug. There's a book called Tripping Over the Truth. I would recommend by Travis Christoperson. I wrote the forward to that book. So there are drugs out there that patients can take that kind of mimic the ketogenic diet. Metformin is kind of one of. them. There's hundreds, like 10 years ago, there probably wasn't even one. Cancer registered clinical trials.gov study on metformin, and now there's like 500 or something

like that on metformin. So the oncology community is waking up and they realize that targeting metabolism is a fruitful path, not in and of itself as a standalone therapy, but to further augment the therapeutic efficacy of different forms of therapy. I'm particularly interested in immune-based therapies. There was a nature medicine paper that came out about a month ago showing a vegan diet versus a ketogenic diet just two weeks. It was tightly controlled on the immune system. So the vegan diet increased innate immunity, and the ketogenic diet robustly increased adaptive immunity. So this is kind of interesting because the adaptive immunity is sort of what, is augmented with different types of immune-based therapies for cancers,

like checkpoint inhibitors, like PD1 inhibitors, Katrina, and things like that. So, you know, Moffat Cancer Institute is very interested in that, and we're kind of talking about different pathways for that. So I am of the opinion that these metabolic-based approaches absolutely need to be coupled with the standard of care. However, I see a path forward where an engine, calculated, modified, supplemented ketogenic diet, if you want to call it that. It's a little bit different than the clinical ketogenic diet used for epilepsy, but there's

a lot of potential for innovation and actually putting together a ketogenic diet that's far more efficacious and therapeutic than the existing ones, I guess you could say. And then we have a whole toolbox of different pulse therapies, right? So the press would be, you know, maybe continuous metformin, modified supplemented ketogenic diets, you know, exercise. There's not enough discussion about a whole field of exercise oncology is emerging. Exercise is such a powerful metabolic therapy, you know, to preserve lean body mass, to enhance metabolic health and function. So that's part of it too. And then the pulse therapies can be, you know, chemo, radiation, immune,

based therapies, but hyperbaric oxygen therapy and also intravenous vitamin C. So IV vitamin C, sounds like a woo-woo thing, but intravenous acorbic acid where you elevate vitamin C levels into the millimolar concentration in the blood. And vitamin C functions as a glucose antagonist. So it actually blocks glucose from getting into the cells, creates in an acute fashion metabolic stress. But it also So it also functions as a pro-oxidant. So on cancer cells, high levels of vitamin C can enhance oxidative stress within a tumor. Within a tumor, you have high levels of heem and free iron. And then that can drive fenton reaction, fenton chemistry.

You don't need to know all the details. But within a tumor, there's much higher levels of oxidative stress. when you reverse tumor hypoxia with hyperbaric oxygen, you hyper oxygenate the tumor, and it's independent of hemoglobin. So hyperbaric oxygen therapy works. Hemoglobin is already saturated, but the oxygen is dissolved in the plasma. And that allows the oxygen to perfuse into the tissue because the tumor has erratic blood vessels where the red blood cells kind of get caught in the blood vessels and the tumor is hypoxic.

But if the oxygen's in the plasma that can quickly reverse tumor hypoxia, hyper oxygenate the tumor, and then in the context of like vitamin C or different drugs, we're kind of interested in something called artemisinin. And there's other like pro-oxidative things that you can get like off the shelf. There's mebendazol, you know, and that could be sort of a supportive therapy. There's a lot of things that could further enhance in a cancer-specific way, the oxidative stress. And it does it in a gradual way instead of the slash and burn kind of method that the standard of care does. And it's not damaging the healthy tissue. So you have the press therapies, which is just transitioning your body to burning fat and ketones and then exercise, meditation, maybe some low-level metabolic drugs like metformin.

And then, like, in a pulse protocol could be done once or twice per week, for example, for like three weeks on, three weeks off, where you pulse, you know, hyperbaric oxygen, IV vitamin C, and then or standard of care if you want to go that route, depending on the type of tumor. But then, I mean, we have like a whole toolbox, essentially, have different drugs and therapies that we want to try. and we're putting together, as Tom Seaford may have mentioned in his podcast, a group of about 40 different cancer biologists, clinicians, and scientists, putting together a whole comprehensive protocol that will describe all this. And we're working on it, it's just way too big now, and we're trying to trim it down and finding a journal to publish it in. And that will give people a framework and a guide.

But it'll be up to the, typically like a functional medicine oncologist or functional health doctor to implement this and work with the patients to implement it. And that's maybe what your listeners are seeking. It's like, okay, well, what's the protocol and how do we implement it? The protocol will be sort of released pretty soon in a lot of the details about it. But then we have to create an infrastructure of clinicians and knowledgeable people that can implement this. Yeah, it's so important.

And I think that part of why, you know, I mean, there's so many questions. that I have for you, we're going to get to it all on today's episode. Maybe not all of it, but we get as much as we can. But part of the reason we wanted to have you on here today is obviously talk about your contributions to the space, how you see all these things kind of coming together. And also, you do a really good job of helping people understand that, hey, listen, these are emerging. Here's the research that's there in mice.

Here's the research that we hope to see in humans. Here's what we know, like in the case of a ketogenic diet, is generally regarded as safe for individuals, right? Like it's something that people can use. And it's obviously used as a therapeutic tool for things like epilepsy, which also you, you know, you have some background in. But that, you know, people should understand that it's essentially, it's still considered experimental. So if you're going to enter into that territory, you are entering to that territory as sort of a little bit of a wild, wild west. And while there may be people that are wanting to only go what would be typically called the alternative route or away from standard

of care, you are super clear that you feel that the best hope for people is to blend these things, like truly in an integrative way. So have a little bit of a team. You know, you have to be the CEO of your health. So you'd have your functional, you know, individuals that would be there, even if they're not a formal oncologist. They have some experience with navigating the roadmap of cancer, modalities and they can ask good questions and they can help especially with the breast pulse side of things and then you'd have your traditional oncology team my mom was diagnosed with breast cancer this was more than 10 years ago and i didn't know about the press pulse protocol and we didn't have a lot of these tools luckily for her it was very early it was caught very early but we still did the same thing

she had her functional sort of team that was there an actual uh functional medicine medical doctor who's a nutritionist as well, who was previously a cancer survivor and was open-minded and taught my mom what questions to ask her oncology team, you know, had her evaluate the therapeutics that were being pushed to her to see, was this really something that would support or was the quality of life degradation so high from including this drug that it wasn't worth, you know, that particular intervention and they could go for a different route that was there. So you're really, what I'm hearing from you is advocating a team approach. It's tough because people want one solution. They want to be able to go to one place and maybe that's the future. We're just not there right now in the

current state of things. Yeah. And I think, you know, modern oncology doesn't even pay attention to nutrition, right? Like nutrition independent of a ketogenic, you know, of a ketogenic diet, like even if you're going through chemotherapy and radiation and it just wreaks habit on your GI system, Just making sure that you're, you know, you don't have any nutritional deficiencies and like B vitamins and restoring gut health and things like that. Like, this is not a conversation that even comes up because usually the recommendations are to eat as much food as possible and gravitate towards more processed foods, hyper palatable foods, so you don't lose weight. So that's the general recommendation. And I think that's, and, you know, on the periphery, it kind of makes sense, but it can do more harm than good. And, and, but what, you know, if you were to do a podcast with me 10 years ago, there was like nothing on clinical trials.gov.

I just gave a talk, just reviewing the PubMed research and also the research on clinical trials. And I just pulled up the website. These are registered clinical trials on using ketogenic metabolic therapies, glioblastoma, pediatric brain cancer, breast cancer, prostate, pancreatic, head and neck cancer, endometrial cancer, renal cell carcinoma, lymphoma. And that's just the ones I'm just pulling up here, just looking through. So 10 years ago, there was like no, maybe one or two glial blast room about 10 years ago. But, you know, people are taking notice. And this is like, I would say, I mean, it's important to preface this, that, you know, the ketogenic diet is used here to enhance a standard of care.

I think maybe one or two clinical trials, it was like, you know, looking at quality of life in patients that were palliative or something like that as a standalone therapy. But the large majority, you know, they're using ketogenic diet to enhance. But that's like, I mean, you have like almost a dozen different types of cancer here being treated currently with a kid. And so people are realizing that this is a viable approach, but we, there's a lot of hurdles to overcome because people are using all different types of ketogenic diets. So we have to universally, and if we're going to do a randomized control,

trial, we have to standardize a ketogenic diet. It's like if you do an RCT on a drug, but you're using, you know, racemic versus this or that are different versions of the drug, then you can't make sense of the data. So we have to universally agree on the macronutrient profile, the micronutrient, you know, the fatty acid composition. And once we kind of agree on a viable ketogenic metabolic therapy protocol, then we can do randomized trials that don't mean something. So I think that's an important conversation, even in the world of like metabolic psychiatry

where we're trying to figure out, you know, the ketogenic therapy that would work best for bipolar, schizophrenia, you know, depression, anxiety, things like that. We need to really nail down. So I think entrepreneurs out there listening to this, I think there's opportunity for food companies to develop whole foods based ketogenic meals that are standing. standardized that can be used for clinical trials and even for clinically. And then ultimately, I'm sure, you know, insurance companies will cover this. So I think it could be a fruitful venture to go down that path.

Let's take a step back for a second and just remind our audience. Why is it that the ketogenic diet could be potentially therapeutic in the setting of cancer in the first place? Like what is unique about that diet and the environment that it creates or helps avoid inside of the body that could be therapeutic when it comes to cancer specifically? Yeah, probably would have been good to start there. Yeah. But so there's multiple reasons for that. I guess I would take a step back in like, you know, the ketogenic diet has been used for epilepsy. Dr. Wilder validated its use at Mayo Clinic in 1921, so over 100.

years of use. We didn't know why it worked. We just knew it. Mimic the physiological state of fasting and changed our metabolic physiology. And changing metabolic physiology changes the neuropharmacology of the brain, changes the fuel that the brain uses too. And that had a profound anti-seizure effect and still has a greater anti-convulsant effect than any other drug probably that we know of. Actually, it's, you know, when all drugs fail, kids are put on a ketogenic diet and it works. So that's sort of a validation, you know, it's work. So the ketogenic diet works. And when I met Thomas Safre, he was like, oh, yeah, the diet works great for epilepsy, but it actually works better for cancer.

Like if they did clinical trials for cancer, it would have better. And I think there's been five or six RCTs on the ketogenic diet already. I heard someone mentioned 13, but maybe I need to update myself. but there's been a number of randomized controlled trials with the ketogenic diet, typically using like a shake, like a liquid ketogenic diet, like keto cal. So for cancer, what the diet does is it lowers glucose availability. So a ketogenic diet is high fat, moderate protein, and essentially no carbohydrates. It clinically formulated.

So you limit glucose availability to the tumor where tumors have ramped up their metabolism. to use glucose as an energy source, but also to biosynthesize molecules, right? For the expanding biomass of the tumor, glucose is shuttled into biosynthetic pathways and lipids too. So you have limiting glucose availability and also you create ketones by suppressing the hormone insulin. When you fast or when you go on a ketogenic diet, your insulin levels drop. And because insulin drops, that stimulates your body to make metabolize fat. And the liver metabolizes fat and at an accelerated rate and elevates acetyl-CoA and other metabolites that feed into the ketogenesis pathway. So the liver

generates ketones, beta-hydroxybutyrate, and acetoacetate, and then they go into circulation. The liver is not very good at using ketones as an energy source. It lacks succinyl co-A transferase. interestingly many cancer cells also lack this enzyme that allows for the generation of ATP. So succinctal coate transferease is limited in the liver because the liver is the site of ketone production. It doesn't suck up. It gets enough nutrients by other means by storing glycogen and things like that. But the ketones spill in circulation.

And then the ketones are not only an energy source to the brain and peripheral tissues, but the ketones are like a hormone. So there's like a ketone receptor, right? The GPR 109A receptor. So they have anti-inflammatory effects. They have epigenetic effects through different seretuan enzymes. They impact the levels of neurotransmitters. The beta-hydroxybutyrate, the primary ketone body, directly interacts with the

histones to actually create epigenetic effects. This is called beta-hydroxybutylacian or kind of studying it in the lab. And these epigenetic effects are sort of cellular, offer cellular protection. They have antioxidant effects when they're activated like superoxide dysmutase and catalase get elevated in healthy cells. So a ketogenic diet rapidly shifts your systemic physiology to compromise growth and proliferation of the tumor. And then it elevates ketone bodies, which is a fuel source that arguably, some people may argue, is not a fuel for cancer cells. I think some cancer cells may be able to use the ketones for biosynthesis, but because, you know, in particular, aggressive cancer that has damaged respiration,

mitochondrial respiration, would just by default, because of the damage mitochondria, would not be able to use the cancer cells efficiently as a fuel source. I think generally most people would agree with that, even people that are not super familiar with that, that, you know, that cancer cells are transformed in a way where they have aberrant mitochondrial function and have more or less defaulted to a glycolytic and substrate level of phosphorylation sort of metabolism. So, so that's like some of the key points. And I do think the anti-inflammatory effects, too, that ketones have. And then just simply being able to protect normal tissues have an important function of someone's going through the standard of care too. And I think Dr. Adrian

Sheck has shown some data where, you know, you give animals, you know, radiation, like whole brain radiation in a state of ketosis and it doesn't like have any negative or severely attenuates the consequences from radiation. So by it's protecting the normal healthy cells. But in the context, therapeutic ketosis is cancer killing and health. helps to enhance the efficacy of radiation therapy and probably chemotherapy too, but I think we haven't really sufficiently studied that. And at the same time, it's protecting the normal healthy cells. So that's like an important, you know, when we view it as an adjuvant therapy, I think

that needs to be appreciated. But everybody that's kind of in this field wants the big vision is to create a comprehensive metabolic-based therapy that can avoid the use of toxic therapies. And I think that's going to be reality maybe in the next decade. But it's going to take some time in research. That's super, that's super exciting. When it comes to, again, going back to this idea, for those that haven't seen the past episodes, but Thomas Avery, he broke down his press pulse protocol.

Later on, we had a case study, again, just a case study, featured of an individual that was working with the Hippocrates Research Foundation. The gentleman's name was Den Stacy. And like a lot of people that work with the Hippocrates Research Foundation, who was, you know, Thomas Safreid would often refer people to. It's a nonprofit, kind of offices based out of Texas and California, who sort of just out of the kindness of their own heart, they don't charge or anything. They're kind of guiding people through this. How do you go through the press pulse protocol? Where do you find hyperbaric? You know, how do you navigate all this stuff? What questions should you be asking your doctor? That's kind of a lot of the work that they do.

One of the things that they were talking about in their podcast that we all had together is that they were saying that specifically when it comes to, you know, cancer, you were trying to use the ketogenic diet as a very sort of technical approach to get the blood glucose into the optimal range that Safe rate had highlighted in his book. Because it's when the blood glucose is, I think it said, you would know better than me, but it's like 70, around 70 is where the blood glucose would be somewhere, 65, 70. Is that accurate? Yeah, in a fasting state or a mildly restricted therapeutic ketogenic diet, it'll bottom out in most people between like 65 and like 75. And then, you know, if I do some certain activities, it may dip down into the 50s. But generally speaking, there's very powerful homeostatic mechanisms that maintain normal blood glucose.

So it's difficult for many people to get, especially when they're stressed out and going through cancer therapies, to get their glucose even under like 90 or 100 under certain conditions, especially if these patients are using corticosteroids like dexamethosone or even chemotherapy will elevate blood glucose. So this becomes a tricky scenario. So actually, we were very focused on developing easy ways to lower blood glucose. And one way to do that is exogenous ketones have a profound glucose lowering effect, like much more than something like metformin. So we develop strategies that could be rapidly implemented to dramatically lower the glucose ketone index,

which is the level of glucose over ketones in millie-muller concentrations. no that makes total sense and thank you for jumping and ensuring that because just to complete what I was sharing is that when Dan was on the podcast with his team at Hippocrates research who are not met you know they are medical doctors but they were not his medical doctors they were more just guiding and making him aware of all the research that was highlighted in Thomas Safefrey's book cancer as a metabolic disease on the origin and management of cancer prevention that what I understood from their team was that to get into that like 6570 range right before you go into hyperbaric which Dan was doing again a case study this wasn't some big trial

three times a week that sort of put the the pressure in a way on the cancer cells that they were more they were more going to be right sensitizes them yeah Is that a symptom to hyperbarat? Is that a correct understanding in the way that I understood what they were doing? Yeah, for sure. You know, I'll actually kind of take a little bit of a step back to our lab research. And when I observed the cancer cells kind of, you know, exploding under high pressure oxygen.

I was like, okay, let's just take rats and put them in hyperbaric oxygen with tumors and see what happens. When we did this on a standard diet, you know, in a group of like six to maybe eight to ten, we didn't see a statistically significant. increase in the tumor growth. There was a trend for less tumor, like smaller tumors, you know, and if we powered it up to like 20 or 30 mice, it probably would have been statistically significant. But a key to hyperbaric oxygen with the standard diet alone has a very mild

anti-cancer effect, at least in the model that we're working on. Actually, other people have shown in Germany and other countries have shown that hygrubric oxygen as a standalone in different models to shrink tumors. But we did not see that. But when we coupled it, like you're saying, the ketogenic diet by virtue of limiting glucose availability, suppressing the hormone insulin, elevating ketones, and also, you know, I don't want to go too much into redox biochemistry because that's what I used to teach and it can get kind of technical.

But there's certain pathways that are significantly attenuated that knock down the defense mechanisms of cancer cells. Like one pathway is your listeners is the pentose phosphate pathway, for example. That generates reduced glutathione and that that is very, very robust in cancer cells, but cancer cells need a lot of glucose to ramp up that defense mechanism. And what the ketogenic diet does is it cripples that defense mechanism and makes the tumor selectively vulnerable to oxidative stress modalities. And that could be, you know, hyperbaric oxygen therapy at the maximum concentration ideally. And then also being in a state of ketosis makes hyperbaric oxygen therapy much safer,

meaning that you won't get oxygen toxicity, which can occur in the CNS as a seizure or in the pulmonary system, right? So, I mean, that's what we study. That's actually let us down this path is this observation that you could increase resilience to five atmospheres of oxygen, which is like super toxic, right? up to 600%. So that was one of our first publications with a ketone ester. It was a particular ketone ester was very, very effective neuroprotection, anti-seizure. Then we ultimately used that ketogenic supplement in our cancer studies. So it had an anti-cancer effect. Yeah. So yeah,

a long-winded way of just saying that, you know, therapeutic ketosis sensitizes the tumor and also makes hyperbaric oxygen therapy. And we think the standard of care, much, much safer and much more highly efficacious. Yeah, super important. And, you know, why I've been wanting to have you on and talk to a lot of people in the space and, you know, safe free to highlight of this in his podcast with us is that I think it's very important while people are aware of these emerging modalities, these new ways, some of the research that's around them, what has been research, what has been research,

what has and hasn't been researched, it's important to not walk away from some of these interviews and think, oh, just the, you know, just reducing sugar or just being on the ketogenic diet alone without knowing all the ins and outs and the technicalities could be beneficial. It may be, it may not be. You know, the people that are talking about it are talking about really approaching this in a very technical way. And I would consider you to be one of them. So it's not to discourage people, but it's more to say that just this idea that you're going

to walk away and just go on some random ketogenic. diet that you're going to piecemeal together and that's going to be how you're going to approach cancer is not what anybody is recommending, right? And that's not what you're talking. It's really talking about a more mechanistic approach and working with a team, including standard of care, to approach it. You know, something you mentioned earlier that you said doesn't get enough attention, and I'd love to put a spotlight on it, is this idea of exercise and specifically exercise in the aspect of maintaining lean muscle mass and the protective element that comes along with that for people both who are dealing with cancer and are kind of working through the standard of care,

but also in helping us potentially mitigate our risk of getting cancer in the future. Let's chat about that for a second. Why is it important and why hasn't it got as much attention as it should be getting? Yeah, well, I'm glad you're bringing attention to that. I do think exercise is an equal or maybe even a more powerful metabolic therapy than the ketogenic diet. That could be a stretch because the ketogenic diet profoundly changes metabolism, but it's very powerful. And I also think that it could couple well with the ketogenic diet and even synergistic, like one in one equals three kind of scenario, right? So when you're in a state of ketosis, if you couple that with resistance training to build lean body,

mass that dramatically enhances your metabolic health. Skeletal muscle is the most important glucose sink. So when we have more of it and that skeletal muscle is metabolically conditioned, it essentially functions as a massive glucose sink to limit glucose availability to the tumor. It also increases insulin sensitivity. So we could essentially have far lower circulating insulin and be able to dispose of the glucose, and then there's exercise mediated glucose uptake independent of the glut floor transporter or it helps to translocate the transporter.

So it's a long-witted way of saying that, you know, your metabolic health significantly improves in the direction that will dramatically improve cancer outcomes, right, when we exercise. And I think that, and we don't say, you know, it's hard to get mice to like deadlift and squat and exercise. I guess you can put them on a running wheel, right? But I mean, I guess I just gravitate towards like resistance training. But there are quite a few studies.

Just look up exercising cancer and also human clinical, randomized, controlled studies with, for example, breast cancer. Just go on PubMed, look up like breast cancer, exercise, outcomes. Like, it's remarkable. I don't know why more people are not talking about this. I need to talk about it more, to be honest. I wish there was an easier way to study it, but we always, of course, we need the funding to do it. But we would love to couple metabolic-based drugs, ketogenic therapies, hyperbaric oxygen, and put these mice on exercise protocols. And I think in that scenario, we could probably cure the VMM3 model of metastatic cancer when we do all this together.

And also, I mean, Tom is very adamant about targeting glutamine as so glucose and glutamine can fuel cancer. anything we're looking at different ways to do that too but yeah exercise that conversation needs to happen and we need to have more high-level funded investigators studying exercise as a metabot therapy and also impacts the immune system too when people ask you not that your main wheelhouse is the space of cancer but people ask you and from your understanding of the landscape that's out there if they're saying you know the top lifestyle habits, components that they really should be prioritizing if they're going to

increase their risk of preventing cancer in the future, right? I think the statistics are close to 50% of adults, a little bit less for women, will end up with a cancer diagnosis sometime in their lifetime. If somebody's out there asking themselves, well, what should I really be prioritizing to greatly minimize my risk, knowing that there are some people that just are unfortunately unlucky. There are obviously genetic components that are in there, but for the variables that we can control, what should we be doubling down on? Metabolic health.

So I know that's a very broad term, but there's a couple of, there's like metabolic biomarkers that are not part of the comprehensive metabolic panel, right? So I use, I think you do too, drew a continuous glucose monitor. And that gives us the metabolic awareness to make the, optimal choices on food selection and also the amount of food to titrate the amount of carbohydrates to achieve an ideal glucose homeostasis, if you want to call it that throughout the day. So improving glycemic control, of course, just simply, you know, a healthy weight, your body composition, increasing lean body mass, reducing body fat.

But also there's biomarkers that we should be measuring, including fasting insulin, hemoglobin A1C, HSCRP, which a lot of cancer patients send me labs, even, you know, when they get the initial diagnosis, and HSCRP is like through the roof, right? So I think, and I don't, I think that's more of a consequence of having cancer going through therapy too, but I think inflammation can drive. We know that. I mean, it's one of the, it's part of that oncogenic paradox, right? where multiple things can cause cancer. And that could be radiation, chemicals, inflammation, hyperglycemia, you know, a whole host of things can cause cancer.

But optimizing metabolic biomarkers, including insulin, hemoglobin A1C, uric acid, HSCRP, of course, you know, keep triglycerides low, blood pressure. You know, I know that's cardiovascular and stuff, but it's just a sign that your metabolic health is good. And that's probably like the best thing that we can do. And we do that through, you know, avoiding, avoiding toxic food, avoiding toxic, you know, relationships, avoiding stress, creating a lifestyle that promotes us to choose, you know, have healthy food choices.

I'm biased towards low carb. And then creating a lifestyle that you prioritize exercise. And it's not like this thing that you do. if you get off work early or something like that, that you build it into your schedule. And I think I grew up just like exercising as part of like what I did. So it's just like a natural extension of my day. You know, I don't do it every day, but I try to fit it in.

And I look forward to it. But there are some people, including cancer patients that will reach out that they just don't like to exercise. So like go to the gym and that kind of exercise. But I think the best exercise of all is just getting out and walking, especially in nature. if you could do it like outside and just in the natural sunlight and stuff too. So I'm a big proponent in just getting 10,000 steps a day. You know, if you just do that, I mean, if they just studied people, like two groups of people and one walked, you know, 10,000 steps a day and another just a thousand steps today,

I think you're going to see huge, you know, differences in preventing cancer. And I think that's a whole other conversation. But listen, you know, some people could do everything right and then get cancer. cancer. And I've met quite a few people that were in great metabolic health. And they ended up getting cancer, like even brain cancer. And they're like, how could this happen to me if it fits sort of the metabolic theory of cancer, right, where healthy mitochondria are the ultimate tumor suppressor. And I do believe that. But then there are a lot of different things immunologically that could trigger cancer. It could be, you know, the papillomavirus. Viruses cause cancer, CMB, you know,

Epstein-Barr virus, you know, different infectious agents that we harbor can damage respiration and could, you know, ultimately damage mitochondria in a way that makes us more susceptible to cancer or hyperactivates or reduces immune function, like our immune system is so busy fighting off the infection that it, uh, uh, and getting cancer is to some extent a failure of the immune system. And if your immune system is like an army, right? If it's, occupied in trying to get rid of a particular infectious agent that we may harbor throughout our lives, that could make our immune system weak in a way that we get cancer. I've been kind of intrigued by that idea, and I think there's a lot of merit to it. But we do know, I think Michael Bishop got the

Nobel Prize, right, for discovering viruses cause cancer. And I think there's a lot of research that should be done on this idea of different viruses that have already been done. And Tom Safer might have highlighted it of viruses that damage respiration that cause cancer, you know. And I think, but Tom has a really good schematic showing all the different things that cause cancer. And I have it, you know, it's in one of a couple of my talks that I recently gave. And I think if people just like look at that and all the different provocative agents

that damage respiration and create a lifestyle to prevent them from doing so will be important. Yeah, maybe we could feature that if you send it over afterwards. You can put on a video for YouTube for those that are watching. Let's go back to the ketogenic diet for a second and just this idea of experimentation. One of the things that you're known for and you've chatted about publicly in a lot of your interviews before is that you're constantly in a place where you're experimenting on yourself and you're playing. with things and you're playing with a different approach. You mentioned that you're biased towards low carb. How has your mind evolved or shifted or sort of broadened a little bit when it came to

that idea of low carb or a ketogenic diet for yourself over the years? I got interested in the ketogenic diet in 2008 and the only book available when you Googled the ketogenic diet, the Charlie Foundation came up. Right. So that was like, you know, there wasn't my much chatter about ketogenic diet at all. And the book that I got was written by John Freeman and Eric Kossoff, who are at Johns Hopkins Epilepsy Clinic. So I got that book and I bought a ketone meter, which was really expensive at the time, and formulated a four to one ketogenic diet. And over the course of like two or three months, I lost strength and I lost muscle. But then it came back. Then my strength and energy levels came back after about like two months.

but realize that a 4-to-1 ketogenic diet is difficult to sustain about a year later, Dr. Kossel. Just as jump in, sorry. Can you just explain what 4-1 means? Oh, yeah. Sorry. 4-to-1 ratio in grams. So four parts fat, one part, essentially protein. So if the macronutrient percentages comes out to something like 87 to 90% fat,

and then the rest of that, you know, 10% essentially protein. So barely low protein, super high fat. And this diet did put me into a state of ketosis. I was a little bit nauseous and didn't really feel good the first week or two. But realize I just wanted to experience the state of ketosis. And then maybe a year or two later, we developed like, you know, exogenous ketones. And we were playing with them and experimenting with them. But over the years, I did see favorable changes.

and cardiometabolic biomarkers, with the exception, if you want to argue, the LDL cholesterol did creep up. I mean, I always had about 100, and then it creeped up to about 300, an LDL 300, and my APOB. So we were talking about that before we got started here. And then, I guess, you know, about two or three years ago, I transitioned to from a ketogenic diet to just a low-carb diet, a low-carb diet being about maybe 70, the highest I'll ever get during the week is maybe 100 grams of carbs. And that will be very high fiber. So it'll be typically broccoli, wild blueberries, walnuts, avocado, maybe an apple here and there. And, you know,

on a higher carb day, it might reach 100, but typically about 50 to 70. And that was enough to bring my LDL from 300 down to 200. And then it has stayed like rock stable pretty much around 200 for almost two years and only recently actually as of today did I get my blood results back from six weeks of a drug called a zetamide which blocks the transporter for cholesterol then it shot it down to 104 with triglycerides going in a favorably lower and HDL a little bit higher so I am of the opinion that elevated LDL even in the context of what's called a lean mass hyper responder and I know And I say that, and I use that term because I know you had Dave Feldman on the podcast before mine. So everybody go listen to that podcast if you're listening to this because Dave's doing some amazing work with the Citizen Science Foundation.

So I am of the opinion now until the science comes out and could potentially validate that elevated LDL that's even astronomically high in the context of the lean mass hyperresponder phenotype, which is low triglycerides and high, I'm of the opinion that the elevated LDL is not ideal. And bringing that down from hyper-elevated to, you know, more normal levels probably would be less atherogenic. But I'm just very cautious in that regard. But other people would probably argue that with me. So my diet has transitioned to more of a low-carb diet that keeps me in a very mild state of ketosis. but I do use exogenous ketones. So basically, beta-hydroxybutyrate combined with electrolyte, sodium, potassium, magnesium, calcium,

and I consume that similar to the element, but the keto-start product is what I use, and the beta-hydroxybutyrate is actually bound to the elements. So you consume it, you get the elements, the electrolytes, and then it releases beta-hydroxybutyrate. And I do that, like, first thing in the morning, and then I do it. it like later like midday. So I'm on a low carb diet, but I get the benefits of being in ketosis by using an exogenous ketone electrolyte, but also MCT. So if people don't want to buy, you know, a ketone supplement, medium chain triglycerides are great. MCT, if you can tolerate it. MCT oil, you can incorporate it into food, into sauces and dressings and things like that.

So, but I do believe that having a diet that has some phytonutrients, and some fiber in it is beneficial. That's great. Thank you for sharing that with us. And like a lot of people, you know, we're all trying to figure out our own health to run along the way and make the best decision. I've also shared previously,

I had the cardiologist that I work with, Dr. Michael Twyman on the podcast. And, you know, I've shared transparently all my labs. I shared my audience along the way. I'm due for an updated episode coming out. And I also told them that I'd come back and share how my metabolic health and lipids improved. Because just like you, we were chatting beforehand,

I also am not excited about the fact that my LDL is very high and my APOB is high. So I made the decision about six months ago to also start a Zetamide at all the options that were there. Even though, again, like you, I'm paying attention to this entire space and people like Dave Feldman, I'd rather not risk in that direction until I have more evidence personally. that, you know, things are okay. On the flip side, I've also, I don't know if you've had any experience with, and no affiliation, I have no affiliation with them. These advanced CCTA scans, like clearly that look at soft plaque and heart plaque in the body,

in the heart specifically. But I had that done when I turned 40, and that also gave me a sense of peace of mind because there was essentially no hard plaque or no soft plaque, like the tiniest, tiniest amount of soft black. that was there. I've heard from multiple cardiologists that it was one of the cleanest scans. Knock on wood, I want to try to keep that up in the right direction. But, you know, I appreciate you sharing about that. So now on more of a low-carb approach, do you're saying a mild state of ketosis by using products like you mentioned like keto start, which is a supplement, right? It's a supplement

form that you're taking. Yeah. Yeah. Yeah. It's a it comes in a package. it comes in a packet and it's just like it's that big, it's powder, you put it into water, and it gives, essentially kind of mimics the electrolytes that you find in electrolyte supplements, but the electrolytes are ionically bound to beta-hydroxybutyrate, which is a ketone molecule. So there are different types of exogenous ketones out there. Many of them in the liquid form are basically based on something called. called 1-3-butane dial. And I talked about our cancer studies

that we saw very favorable effects of exogenous ketones. And that was actually 1-3-butan dial. And then 1-3-butan-dial-based ketones were also efficacious. And then the ketones, the electrolyte ketones, can also work too. We didn't study it at the time because we didn't have this particular formulation.

But I do worry about people taking one, so most of the supplements, liquid supplements on the market are 1-3 butane dial, and that is a dye alcohol. It's a glycol. When you consume it, the liver needs to break it down. You do create a beta-hydroxybutyrate aldehyde. So the liver needs to break that down to create ketones. And it also has a mild kind of, it gives you a little bit of a buzz, a mild narcotic effect,

and it tastes kind of bad, too. So, but it has, I mean, we've studied it, you know, it has some interesting effects, but it doesn't like enhance performance. It doesn't may give cognitive, you know, performance. under certain conditions. But there's a lot of hype around marketing for that. But what I tell people is to gravitate more towards a ketone electrolyte supplement, like Keto Star and also MCT.

MCT is medium chain triglycerides are if you, you could take a low carb diet and just eat, you know, three or four low carb meals and add one or two tablespoons of MCT. And then you've created a ketogenic, a Mediterranean ketogenic. diet if you want to call it that. And then you could use a ketone. If you take exogenous ketones with MCT, that can shift the pharmacokinetic curve to the right, I would say. So you get a greater sustainment of the ketosis over time because the fat delays gastric absorption. If you take the exogenous ketones with protein, fiber, and fat, it's going to delay gastric absorption,

and then you get ketones throughout the course of the day. So this is essentially what I do. like working in academia i stay ketogenic all day and then you know for my dinner i'll have some veggies and then maybe some fruit and stuff at night but essentially i am sharper and more have more clarity of thought and more energy throughout the day staying very low carb or keto and then i'll kind of backload some carbs like later in the day after my evening walk or right before my walk and then a little bit after my evening walk that's my typical routine yeah that's what i was going to ask you again, we're talking about you. We're talking about your sort of situation. I was going to ask you, what is the primary driver that you want to stay in a mild state of ketosis, especially in the earlier

part of the day? And you answered it is that it's kind of keeping you sharper. It's giving you more energized. Do you feel like there's any therapeutic benefit to that for your sort of long-term health that you personally are doing this well? Or is it primarily how you personally feel on a day-to-day basis? Yeah, by restricting glucose availability to your peripheral tissues, you're forcing your mitochondria to work harder. So that's stimulating mitochondrial biogenesis, mitochondrial efficiency, and also by keeping a state of mild ketosis, those ketones have anti-inflammatory effects. I did an experiment where I stayed in, you know, just a moderate ketogenic diet, low-carb ketogenic diet,

like I described. And then I transitioned to a very healthy health. the low moderate carb diet 200 to 300 grams of carbs a day so relatively kind of high but it was you know vegetables some fruits and then I bowed I got I popped off my carbohydrate intake with with lentils I think because these were like the most healthy carbohydrates you could choose so I wanted to do and I clamped my weight and so I clamped my calories and also kept my weight stable throughout throughout those weeks. And then I did blood work again. Actually, my insulin stayed the same. It didn't go up or down. Hemoglobin A1c trended to be slightly higher. But my HSCRP went from like

non-detectable or zero point one to one. And that was an indication that those plant foods may be like, you know, it could be the defense chemicals. It could be what I think it was doing is not making my gut, making my gut slightly more permeable, I guess you could say. And a lot of people do gravitate toward like a carnivore diet or ketogenic diet because it helps their gut. It reduces small intestinal bacterial overgrowth or something like that. And then I've done this experiment like more or less a couple times in that, you know, my level of inflammation is like really, really low when I stay in this mild state of ketosis. And I think that, you know, if you're, that'll pay big dividends over the course of like decades. Like, you.

keeping inflammation very, very low. However, if I, you know, get like, you know, a couple weeks ago after traveling and we hosted the metabolic health summit, I was in contact, I contracted COVID, as did many people, like, in the lab. And, you know, two days, I shook it off, but I saw my CRP pop up. You know, I had like, you know, inflammation would be normal and when you're fighting an infectious disease. So, but I just throw that out there because, you know, I've tried a lot of different diets and I always gravitate back towards low carb or semi-ketogenic and with some supplementation now. And I wouldn't, if I transitioned back to more of a carbohydrate-based diet, I think there's going to be some unfavorable changes in other biomarkers that I think are more important.

I think keeping a low HSCRP is more important than the consequential elevation of LDL, which we could knock that down with something like a Zetamide, right? So it's a learning process, but I'm always experimenting and just trying to find, you know, what's right for me. Yeah. You know, I was just curious myself about you, which is why I was asking so much of what you do. But I also want to make sure for our audience, because we have a lot of people listening today, is that you've also shared that for the average person that's listening, regardless of what diet they follow, the most important thing is to make sure that when it comes to the dietary side, like they're maintaining a healthy weight and generally as much as they can skew towards whole foods, that a lot. is going to be giving them, you know, a very, it's going to be a huge step in the right direction. So people can personalize.

They can do a lot of different things, but for people who might be confused or feel like they do better one way or have to eat a particular way because of religious or ethical reasons, keeping a healthy weight and making sure that you steer towards whole foods. And obviously because you're such a big fan of making sure that the skeletal muscle is being fed, getting the adequate amount of protein that you need to make sure that the body is. is supported. Is that correct in me summarizing some of your broader thoughts outside of your own personal experiences? Absolutely. Yeah, you hit like all the important things. And I generally just love like resistance training, weight lifting. So that has become a part. And I appreciate it more now

as I'm getting older because it becomes harder, you know, as I'm, you know, pushing 50 to keep that, keep that muscle and strength up. So I've over the years of being ketogenic increased my protein from like, you know, 1.2 grams per kilogram now. It's like more like 1.8. So it's pretty high protein. But I also do a yearly dexas scan to look at just my lean body mass and bone density. And I think, you know, dexes are pretty cheap now. I guess years ago, they were more expensive. But for 75 bucks, you can get a dexas scan. Doing that once a year and that lets you know if you're on the right track. You know, I did. The dexas actually what led me to realize that, A lot of intermittent fasting and strict keto, I lost something like 18 pounds of lean body

ments over the course of, you know, maybe five to six years. And I was like, I need to I need to course correct for that because I can't go down that trend. So I started, you know, eating breakfast and just spreading out my protein a little bit more, getting more protein. And then I did take a year off of like weightlifting and training when we bought a farm and I was doing a lot to work outside, but, you know, getting back to training and stuff, I was able to reverse that and actually add lean body mass, even at a relatively advanced age, if you want to call a late 40s advanced age. Well, you brought up another really great point that I just want to touch on for a second is that

when we were talking about, you know, the usage of certain things like supplements sort to enhance, you know, if somebody wanted to enhance and kind of instigate inside of the body a mild state of ketosis, it's much easier to do with these supplements than just dietary patterns alone, because for a lot of people who are hearing the recommendations of eating enough protein, making sure to get enough calories for their body to be able to function, especially now that they might start including in some resistance training or working out, if they were just trying to enter into a mild state of ketosis alone just through food, it'd be very difficult, they'd end up having to cut back, and then their different aspects of

their body could end up suffering like losing muscle, as you saw in your instance and situation. So that's probably another reason you're using some of these supplements to support you in the process of sort of instigating mild state of ketosis. Is that accurate? Yeah, yeah. There are like real benefits to, you know, some of these supplements. Creatine monohydrate is probably like, you know, an important supplement. I didn't talk about probably one of the most important omega-3 fatty acids if you don't eat fish. I also recommend the omega-quant test to look at your omega-3 kind of profile. And I take alpha-lapoic acid and melatonin at night, kind of a short list of supplements.

But yeah, the keto start is what I use by audacious nutrition. And the electrolytes really, I think you do get depleted. I see this on blood work. People get depleted of electrolytes, especially calcium. believe it or not. Maybe it's calcium's kind of lacking in the soil. I know we have a farm. I know it was like deficient in our soil. And a lot of the food that we eat is deficient in magnesium and calcium and things like that. So something like a ketone electrolyte supplement would be giving you your electrolytes, which when people start a ketogenic diet, sodium drops pretty low. That's called

a naturitic effect and it has a diuretic effect. So what people may experience, is that they go on strict keto or even during fasting and they get up and they get what's called orthostatic hypotension. That's the contraction of their plasma volume just because there has a diuretic if they're not drinking enough. A lot of people like drink a lot of coffee too when they do keto just to wake them up and get through the keto flu brain fog kind of thing until they adapt. And so yeah, you want to stay really hydrated exogenous ketones can help you punch through that keto flu where you don't even experience it. You just have to stay. energy right off the bat. And then for me, I really would need to dial my carbs back a little bit

more to stay in what I think is like that optimal therapeutic ketogenic range, which is really just like one millimolar. And a lot of people, there are people that, you know, even people that sell ketone supplements or the exogenous, like the ketone esters say, you need to get up the three or five millimolar. We are not of that opinion, especially the research that we're doing. And it basically higher is not better. And you can achieve one millimolar, probably with MCT. You can definitely achieve it with like keto start and one packet of keto start and maybe 30 to 50 milliliters of MCT a day.

You can get well above that, not even on a ketogenic diet. But once your ketones get above like two, three, four, that can actually cause energy toxicity. It's like the same reason like you don't want high glucose, right? Because that represents energy in your system that your body needs to really, dispose of. So we have ketone urea. And then those ketone bodies are also mildly acidic. So your body has to produce and dump off more bicarb through the kidneys. So higher is not better when you're talking about exogenous ketones or ketone supplements. So I think that's important.

And it may, our publications may give the wrong impression because when, you know, our first publication is on CNS oxygen toxicity, like this is an extreme environment, but the neuroprotection was at like four to five millimolar, right? But that's like five atmospheres of oxygen. It creates a massive oxidative stress. It's way above what you'd get through hyperbaric oxygen therapy. And, you know, we gave a very powerful ketone ester to four or five millimolar and it had these remarkable effects. So I do think, I mean, we're doing clinical trials right now with, you know, certain things and where we do want to get higher levels of ketones. But for the general person, if you could get your ketone levels to like one or one point five, you are

getting a ton of benefit from that. Like no one eating a standard diet would ever get to that. This is an order of magnitude higher than you typically achieve. So you're getting brain function effects, anti-inflammatory effects, and even epigenetic effects, just getting to like one to 1.5 millimolar. Don't have to get to like super high. And I think that's, there's a little bit of point of confusion and contention around that. Well, while we have a little bit of time here left, I just love to talk about measuring for a second. You know, I'm always transparent with my audience about different stuff that I've done that I've not done. I actually never measured my ketones.

I've always had good general energy throughout the day. I'm taking certain ketone supplements at times. I followed a very messy ketogenic diet when I had first heard about it that wasn't standardized in any sort of way and probably wasn't actually leading me to be into ketosis, right? and was just doing a lot of what I had heard from other people, like a high fat diet and this and that. And I probably actually wasn't even in ketosis to begin with, knowing how hard it is to get there

if you're not using some type of supplement or if you're not very strict with it. So when it comes to the basics of measuring, and you chat about that a little bit, would somebody go about, you know, even getting a baseline to start off with? A lot of the urine ketone measurement strips get like poo-cooed a lot. But I'm actually, you could go to CBS or Walgreens or, you know, Amazon and get these urine ketone strips for like 25 cents per strip. It probably works out. So super cheap.

That'll semi-quantitatively tell you if you're in ketosis or not. So maybe that's like if you don't want to spend money. Although like I have the keto mojo meter here and this does glucose and ketones and it's maybe like a dollar, a strip or something like that. And this is kind of like the gold standard for like the point of care. And it also gives you your glucose ketone index. So we use that device for our human clinical trials. We've also used the Abbott Precision Extra, but the strips are a little bit more pricey.

But we did our initial studies for that with that because the keto mojo was not out yet. So these are devices you can get at any health food or any any, any drugstore, Walmart, or even online on Amazon. on and that it'll give you a lot of insight just measuring like your fasting glucose and then your post-pranillo glucose 30 to 60 minutes after a meal will give you insight into how that meal is impacting your metabolism. Of course, you could also use a continuous glucose monitor and like levels health is, you know, really creating an app and coupled with a glucose monitor sensor that it's very helpful. I use it.

I'm an advisor for them. I think that's a great system. But also, I also tinker with, I have a lactate meter and looking at like my lactate threshold for exercise will give you an indication of your metabolic health. And as you build a more robust metabolic health, you'll see that number move quite a bit. But we're using it more for research purposes. But a standard keto mojometer for, you know, I don't know, like 40, 50 bucks with some strips. That'll keep you occupied and will give you great insight into what you need. to do to dieterally or supplementally induce and sustain therapeutic ketosis. And then the app is

wonderful too for the keto mojo. So that would be probably the only measurement tool that you need to really scientifically do the ketogenic diet correctly. And of course, there's a lot of books out there that can guide you and a lot of websites too. That's great. Just in terms of, you know, there's a lot of advice that people here on podcasts, including my own. And there's a lot of advice that's out there on social media. In terms of order of operation, and in terms of, you know, a lot of the context of the things that we talked about today for people who are going down the pathway of like generally wanting to be healthy, prioritizing their metabolic health, I'm excluding people that might be like dealing with,

like, cancer in some sort of way and really need precision sort of approach with the team. Ordered operations, you know, number one would you say is like even, getting a baseline of your just standard metabolic health and a lot of the labs that are, you know, you might have not gotten recently if your doctor didn't sort of push for them. Is that, is that number one for people in terms of order of operations? Yeah. If you, and I have to remind myself of this that my insurance cover insurance company covers like, you know, yearly or maybe even twice yearly to get that, that yearly doctor's visit and

comprehensive metabolic panel, CBC and CMP. But what you can also do is say, hey, doctor, I, look, look at this paper. Apo B is a better indicator for atherogenic risk than LBL. Can you include that on that thing? And, you know, you can talk your doctor into including certain tests that actually should be covered by insurance and maybe even insulin too. You can kind of make the argument. Well, someone told me the other day, I just told my doctor that, you know, we have diabetes

in the family, so he added insulin and then my insurance covers it. So I think that's a conversation you should have with your doctor to get that yearly checkup, you know, including fasting insulin, hemoglobin A1C, HSCRP is, I mean, really helpful to to track things, especially if you're doing anything different or trying like a new drug or you just don't feel well, too, I think maybe. Then you could do some more advanced testing and there's other companies out there like Genova Diagnostics that I've worked with in different, or ZRT Labs, they have home kits where they have a cardio metabolic panel. You don't have to go to a lab and you could put drops of blood on a blood spot card,

put it in the mail, and then they email you the results back. So ZRT Labs has the cardio metabolic kits. We've used that in research. I validated it. I've done the card at Genova Diagnostics and then got my insulin and other things measured and then it correlated. but had to do that because we did research in extreme environments where you can't do have a phlebotomist take blood. So the cards came in handy just doing a finger prick.

And if you don't like to go to labs, you know, this is really useful technology. And, you know, Abbott and Dexcom now, they're creating kind of over-the-counter, you know, continuous glucose monitoring systems. I'm doing the paperwork for Abbott Lingo, which would be continuous ketone monitoring, continuous lactate monitoring, and continuous glucose monitoring. And I think this could be, I'm super excited because of the clinical, the value that this could add for certain clinical scenarios for people metabolically managing certain disorders, I think, could be super valuable. But I also think that this could be the future for optimizing metabolic health.

So these continuous values coupled with periodic testing. Incredible. I got to look into that ZRT laboratory. So similar to like an omega-quan. We've had Dr. Bill Harris in the podcast, and that test I credit as being a big sort of awakening for me. I had been on a vegan. I grew up vegetarian for a long time, did that test.

So that in my mega ratio, this was now when I was probably like 26, 25 years old, was, I felt great initially on the vegan. diet. And then after years on it, I was on it for like about seven years towards the end, like year five, year six, I wasn't feeling as sharp. I wasn't feeling, you know, as like focused. And obviously I didn't know as much, you know, that I know today. And there's better ways to do to vegan diet than kind of how I was approaching it. But I did the mega quant and it was like, wow, my omega index is completely off. I started including fish, high on fish inside of my diet. And I felt like my brain turned on for the first time. So that's for anybody that's done.

that or wants to do it's like a $59 test you can do it from your home but you're literally pricking your finger and you're putting it on this card so you're saying zrt is giving you know insulin CRP all these markers a one C on kind of a similar thing you're just putting blood drops on a card yeah yeah i got boxes of them here we so that that's one way to do it i don't it's not probably as accurate the triglysteroids were a little bit off but everything else was pretty similar. And, you know, it's not, it's not super cheap. It may be, well, levels, for example, they have like your CGM and now they have all these cardiometabolic biomarkers, including uric acid, APOB and everything. And that's actually cheaper than, so it might be cheaper to go

through that than to get the ZRT Labs does have the blood spot card. And that's kind of a convenience thing. And we did that basically because, you know, our IRB wouldn't approve someone taking blood in certain underwater extreme environments where we were doing research. So it got me turned on to these blood spot cars. But you could do hormones. You could do, yeah, so that's one option. And these technologies will probably get cheaper. But ZRT lab's been around since like the 1990s. And, you know, I'm a fan of what they're doing, Genova Diagnostics, too. And, There's a number. And of course, what levels are doing with their cardio metabolic suite of things and then coupled

with CGM, it builds into the app. And then you have basically like a dashboard. So that's kind of like, you know, the ultimate, you know, an optimizing metabolic health scenario. That's great. No, I love all those. I love levels. I'm an investor, loose level advisor when they need me.

And I think they're doing great work. Shout out to levels. We put the link for them in the show notes below. Cool. Dr. Agostino, I want to come back to, you know, a little bit of what we were talking about at the beginning of the podcast, which is this sort of new frontier of the integrative approach to cancer as we're winding down over here. You know, a big part of this is that if someone is diagnosed with cancer or has a family member and they start to remember that there's these episodes, you know, with individuals like yourself or Thomas Seyfried or other. people that in this space, the metabolic approach, they're often one of their first questions, since it is a little bit of a wild wild west, and some of these approaches are considered still

experimental that are there. And again, you know, just everybody knows you're advocating for them to be used along with the standard of care. A lot of what they're looking for is they're looking for communities. They're looking for communities of people, whether it be other patients that have gone down that journey or they're looking for communities of potential practitioners. Where do you typically tell people to look or sort of hang out that they can find people so that the journey of becoming the CEO of their own health doesn't feel as lonely and they only have to rely on sort of podcasts and YouTube, you know, which could be good or it could be that, right? Any places that you recommend that they hang out either online or offline to start meeting

more people that could be supportive for them down the pathway? Yeah, you know what I do? Because some people contact me with all sorts of different disorders and different types of cancer. The Institute for Functional Medicine usually has, you know, a lot of different open-minded doctors that will be able to work with you in different capacities and implement some of the approaches that are consistent with metabolic-based therapies, like for cancer, for example. But what I actually just kind of go and have advised people to go right to PubMed and see what clinicians are publishing case reports, you know, actually like in the academic literature, so they're practicing as a clinician and they're publishing. And that that's kind of like a high bar. But if you could find a particular clinician near you that has legitimate, you know, peer-reviewed publications for treating a particular disorder, whether that be cancer,

whether that be, you know, we deal with inborn errors of metabolism, for example, that and where it could be like more rare. That's kind of like the go-to place where I, and people may have not thought about that as a resource, right? It's just like going and looking up renal cell carcinoma or glioblastoma and like what clinicians are publishing case reports and getting amazing results on these case reports. And a lot of times it kind of does start out with like someone publishing case reports and then people realize, oh, there might be something to what this person's doing. And they have, you know, a published track record of success in treating this particular thing.

So that's kind of what I have been pointing towards people, pointing people towards just like go to the literature and find out who's having success treating your particular type of disorder. And then kind of start from there. And then you might find out what protocol they're using. And then you can reach out to different functional medicine doctors who, usually are a little bit more open-minded in working with you to prescribe certain things, whether it be hyperbaric or particular, you know, metabolic drug to implement, you know, more of a comprehensive protocol.

That's great. I never would have thought of that, but that makes so much sense is to look up some of these case reports, see who's there, see who has experience. I'll throw in another resource that I've shared with my audience that was very helpful with my mom's journey and a few other family members as well. it's i don't know if you've come across uh the gentleman but his name is ralph moss ralph moss he yes yeah yeah the moss report right didn't he have like the moss report like a long time ago i remember reading and he used to work at like dana farber or something like that too or her slum caterering

yeah yeah he ended up leaving and he went down the pathway of researching everything that works and doesn't work when it comes to integrative approaches for all the different types of cancers because as experts on this podcast previously have shared and Dr. Moss shared, many cancers are almost like their own disease and they need their own sort of, you know, even though we lump them in as cancer, they're, they can be completely different in sort of how they, you know, respond to certain modalities, both standard and integrative. So there's the Moss report.com, which now I believe Dr. Moss's son is really, you know, running Ben.

And they have a practitioner database of different people and inside of their, I've had a few friends that have found like different individuals that have experienced with metabolic therapies and some of them are functional medicine doctors or other or just open-minded doctors that have gone down this rabbit hole often because their own family member had suffered with this and that's how they got educated about it. And then of course, we mentioned we'll link to the episode, but Hippocrates Research Foundation, they've published a few case studies following the Safe Free Protocol. Again, just case studies, super experimental for individuals that are out there.

This has been fantastic. I really want to acknowledge you for all the work that you've done over the years to contribute to this space and how you not only share about what's emerging, what we should pay attention to, but how much you also are willing to experiment on yourself and transparently sort of share with the audience how you've shifted your approach over the years. I think that's very helpful for people who are, you know, following along. If our audience wants to keep in touch with you, what's the best place for them to follow all things in the world of Dr. D. Agoste? Yeah, well, you can look up the research on PubMed just under my name. And then keto nutrition is our informational website to go to. And we have a blog on there. We have resources for doctors, including oncologists.

I probably need to expand that list of people. And then I'm also the co-host of the Metabolic Health Summit, which just happened in Clearwater, Florida. So that's a conference that we hold. And we have an educational platform that's ACC accredited. So we have a vision of being able to train practitioners on metabolic-based therapies, and that could be metabolic psychiatry, metabolic oncology. You know, that's the vision. And we're kind of building that platform out.

the Metabolic Link podcast, which is a podcast that I co-host with my host, Dr. Angela Popp and Victoria Field. So Metabolic Link podcast, Metabolic Health Summit, Ketonutrition.org are all places that you can find me and the information that I put out in our lab puts out. Amazing. Dom, thank you so much for coming on the podcast and sharing about your journey and adding to the wealth of knowledge that our audience has been hearing about when it comes to Safe read, your incredible work around hyperbaric, reminding our audience about the power of skeletal

muscle mass and why it's so important to prioritize, whether you have been diagnosed with cancer, unfortunately, and my heart goes out to everybody who has, or whether you're trying to increase your likelihood of not getting it in the first place, and all the incredible, all the resources that you can share. It's been a true pleasure to have you on today. Thank you, Drew. Yeah, it's been a pleasure, and I appreciate you giving me this platform, talk about our research. It really makes a difference being able to get out there. and tell people about, you know, the work that we're doing and that other people are doing, too, on medalloc therapies.

Awesome. Thank you so much. Thank you. Hi, everyone. Drew here. Two quick things. Number one, thank you so much for listening to this podcast. If you haven't already, subscribe, just hit the subscribe button on your favorite podcast app.

And by the way, if you love this episode, it would mean the world to me. And it's the number one thing that you can do to support this podcast is share it with a friend. Share it with a friend who would benefit from listening. Number two, before I go, I just had to tell you about something that I've been working on that I'm super excited about. It's my weekly newsletter, and it's called Try This. Every Friday, yes, every Friday, 52 weeks a year, I send out an easy-to-digest protocol of simple steps that you or anyone you love can follow to optimize your own health. We cover everything from nutrition to mindset, to metabolic health, sleep, community, longevity, and so much more. If you want to get on this email list, which is, by the way, free and get my weekly step-by-step

protocols for whole body health and optimization, click the link in the show notes that's called Try This or just go to Drew Perot.com. That's D-H-R-U-P-U-R-H-I-T dot com and click on the tab that says, try this.