Dr. Seyfried and Dr. Dom D'Agostino reveal hard truths about cancer

So, hello everyone, and welcome. This is the first discussion of a small series we're doing for Dr. Safereed's official YouTube channel. Uh, where we're aiming to get Dr. Safe discussing his research with other researchers in the field. And today, we have Dr. Dominic Di Austinino here as a guest with Dr. Thomas Safeed to discuss their research together. My name is Morgan, and I'm a student of Dr. Safe's. I've been following his research and his colleagues' research for about three years now, and I'm here to help the Safe Reed Lab get the message out to the public through YouTube and Instagram. And so, I'll give just a brief disclaimer as well, that this discussion isn't meant as medical advice, but rather a discussion of the science. And I'd like to introduce our guest, Dr. Dominic Di Austinino, first. He is a researcher and a professor at the University of South Florida, and the Diagosina lab conducts research to understand the efficacy and mechanisms of ketone metabolic therapies on various diseases, primarily cancer, which we'll be discussing today. And as you all know, Dr. Safe is a professor of biology and a researcher at Boston College, whose lab examines metabolic therapies such as calorie restriction, fasting, and the keto diet, and the mechanisms by which these help manage chronic diseases such as cancer. And so, welcome to you both.

>> Great to be here. Thank you, Morgan.

>> Yeah, thank you very much, Morgan. It's very nice that you're arranging this.

>> Thank you. So, I'd like to begin with the first question, which is, when and how did you both start to collaborate on research?

>> Um, I could start out. So, I was actually familiar with Dr. Safe Freed's research on seizures, and uh, and I think I have been studying uh, central nervous system oxygen toxicity seizures for a little over 20 years, uh, funded by the office of navy research. So, oxygen toxicity seizures occur with really high levels of oxygen, and it's a limitation of hyperbaric oxygen therapy. So, the guidelines sort of are capped at three atmospheres because of the potential for tonic-clonic seizures that happen when you go above three atmospheres of oxygen. Uh, and it's also a limitation for our special operations community that use a closed-circuit rebreather that the Navy Seals. So, being funded by the Navy, they wanted to understand the cellular and molecular correlates of CNS oxygen toxicity, and I started that research in 2004. And anti-seizure drugs really don't provide a whole lot of efficacy for preventing these seizures. Uh, only when you use dosages that basically put put someone into a sedated coma almost. You have to use really high dosages to block these very powerful seizures. I went through a nutrition course in undergrad, but didn't really uh, the ketogenic diet was not talked about. But I stumbled across the Charlie Foundation, which was really the only website that came up, you know, at that time, and saw ketogenic diets uh, could prevent seizures. And then I stumbled upon Dr. safe's work in 2007, I believe, and a year after that, he had published an article on uh, cancer studies looking at calorie restriction and a restricted ketogenic diet and cancer. And then I became increasingly interested in that uh, as we, and I could talk about it later, we observed a number of different cells, you know, in high-pressure oxygen. And we curiously observed these cancer cells uh, were generating significantly more oxidative stress or superoxide anion, and we had different dyes for that, and they were dying at a level of oxygen that was relatively non-toxic to healthy cells, and I did not understand why. And then uh, and I talked to a number of different people, and then a couple years later, I talked to Dr. safe freed, and his theory that he was advancing was really explaining what I was observing under atomic force microscopy and laser scanning focal microscopy when I was looking at the mitochondria. So, then and that that from that, that kind of spearheaded uh, or launched our discussions and then ultimately our collaborations.

>> Yeah. And and I can attest to that because I think we had an opportunity to meet at at one of the, a couple of the meetings uh, that were run by the Charlie Foundation. There was one in particular in Liverpool, England, uh, when when Don was first starting to get these observations together, and then we started to collaborate uh, with the possibility of gaining a better understanding of the molecular mechanisms by which oxygen stress um, might be affect a a non-toxic therapeutic strategy uh, for managing uh, certain types of cancers. And then it, it became more and more clear to us that uh, radiation uh, would kill cancer cells by creating oxidative stress, but but in a in a non-specific way, by by creating reactive oxygen species as as a kind of bombs in the micro environment. And if a cancer cell happened to be near that, uh, it would be blown up. But with um, high pressure uh, oxygen therapy, hyperbaric oxygen therapy, it's, it's seemed to be more um, selective for killing the cancer cells. As Don mentioned, the normal cells seem to be uh, more uh, resistant to this, and and and we know that the cancer cell, having insufficient oxidative phosphorylation, by nature, uh, produces more ROS. Um, the problem, of course, is that their utilization of glucose and glutamine uh, are metabolized to high levels of antioxidant protection uh, through glutathione and superoxide dismutase and things like this. But we, we just, we thought then, if we would lower the glucose and the glutamine, that would be uh, their metabolites like glutamate from glutamine, and through the pentose pathway uh, from from glucose carbons. If we could lower the two fuels, uh, and then expose organisms, can mice uh, that would have cancer to this higher pressure uh, oxygen utilization, it might be more selective for killing the tumor cells. And and we were beginning to see this with Dr. Poff, who worked with Dom. Um, and we were starting to see that, wow, uh, this could be a really effective, non-toxic way, as potentially a substitute or together utilization with radiation therapy, because the ketones would protect the normal cells, but not the tumor cells, and the tumor cells would be made more vulnerable uh, to oxidative stress. So, together uh, with the late uh, uh, Dr. You and and Joseph Maroon uh, from the University of Pittsburgh, we put together a press pulse strategy where where Dom and I discussed how we would, how we would take this whole cancer problem and and and and break it down to a manageable, a very manageable disorder, knowing full well the fuels that were driving it, and the uh, vulnerabilities that we could realize once we would press down the fuels and pulse the fuels driving the disregulated growth, and then make them super susceptible to hyperbaric oxygen and calorie restriction and things like this. And so far, it seems to be working really, really well, better in people than in mice, which has always been one of the great things that we've that we've been able to find and do. And I realize that in the in time, uh, press pulse therapeutic strategy will become the standard of care. The the issue of course is, it's not uh, broadly recognized, nor are the mechanisms that do and I have been talking about also broadly recognized. But once they are, it, it to me, has all of all of the power to manage cancer uh, very effectively, and also gives us the opportunities to bring in all kinds of new approaches that work together with the pressing uh, of of the glucose fuels and the pulsing uh, of glutamine fuels, together with hyperbaric oxygen, a variety of other strategies that we're now beginning to realize for the first time are effective. So, the collaboration uh, is working very, very well and is and is continuously improving. So, uh, would you agree, Dom?

>> Yeah. Yeah. Absolutely. And I, I think I'd like to add too, that, you know, even before engaging in a discussion um, with you, Dr. Dr. I, I talked to a number of people at the Moffett Cancer Center, I, and a number of cancer investigators, and u, they did put on my radar the Warberg effect, and they kind of said, well, there's this guy that, you know, he's, he's very kind of out there and advancing a theory that's a little bit controversial, but his name is, you know, Dr. Thomas Safe freed. And then I, I, I think the article came out in 2010, cancer as a metabolic disease, and nutrition and metabolism. And it was after getting that article and just reading it over like five times and pulling out all the references, saying, this is extremely compelling. And prior to that, we observed that high pressure oxygen causes uh, a massive increase in superoxide in these, in a number of different cancer models, including a GBM model, and that they die faster. And and that we measure superoxide with mitos red and dihydrotheidium. So, we knew it was coming, like from the mitochondria, but I didn't understand why at the time. And I was also looking at something like 2D deoxy glucose and different glycolytic inhibitors, which can also be used for the anti-seizure effect. And noticed that we're trying to grow these different model cells. And it was easier to work with these immortalized cell lines, these cancer cell lines. And just, it was causing, you know, reducing their growth and increasing um, their cell death. And so, essentially, we observed that that blocking glycolysis, reducing glucose, or using a glycolytic inhibitor, you know, significantly impacted these cancer cell growth and increased cell death. And oxygen was toxic to the cancer cells. And then what was really interesting is that we kept glucose at the same level, and when we added ketones, we saw an increase in uh, cancer cell death with ketones. And it also uh, suppressed their proliferation.

>> And we used uh, the D and the L enantiomer of that. So, and that's that's kind of another story we can get into, because I'm very interested in that. So, the observation that ketones had an anti-anti-cancer effect, that reducing glycolysis had an anti-cancer effect, and that hyperbaric oxygen had a cancer-killing effect. So, we saw the opportunity to sort of combine these things in a synergistic way that could be non-toxic. And that essentially became the PhD dissertation project of Dr. Angela Poff, uh, who who came into my lab with a high interest in cancer, but I had not been studying it. You know, I had a little bit of startup funds. So, that kind of kicked off, you know, some some studies. And then ultimately, I had requested Tom, I don't even remember that, but I wanted to do very specifically a brain cancer model. And then you talked me into the VM M3 model of metastatic cancer. And I was like, well, I really want the brain cancer model. It's like, no, you have to work with this [clears throat] model of metastatic cancer. And I remember it kind of made the the front page of International Journal of Cancer or something like that. And I remember reading that and I was like, "Okay, this is a good direction to kind of go into." And then that, I think it was about 2010, we actually kicked off >> with experiments using your models.

>> Yeah. Well, I, I think the the VMM3 model is a brain cancer model.

>> Yeah.

>> Uh, but it also metastasized outside of the brain.

>> Yeah. It's a good point. Yeah. And and the issue, of course, I ran into a lot of problems um, in trying to get uh, grant NIH grant support for that model, because the reviewers said, oh, uh, GBM doesn't metastasize, glioblastoma doesn't metastasize outside the brain. And then I said, what, what do you, what do you mean? I said, I have 70 articles here that that you are unaware of, showing clearly uh, that glioblastoma does, in fact, can metastasize outside the brain. And they stopped doing organ transplants from patients with GBM, because the recipients that were getting these organs developed metastatic cancer. So, where, where did that come from? Uh, it came from GBM cells that had metastasized outside the brain. Um, but for whatever reason, the field seems to be locked into these preconceived notions, and we're resistant to the idea, uh, of this this concept that um, metastatic cells uh, can occur in glioblastoma. As a matter of fact, the most invasive and spreading cell of the GBM is a mesenchymal neoplastic mesenchymal cell, which we think is derived from microglia. So, a neoplastic microglia cell are loaded in some of these GBMs, and they have the they have the capacity to spread into the bloodstream and spread throughout the body, but in small numbers. And a lot of GBM patients unfortunately die before they recognize cancer cells outside of the brain. So, but the issue, of course, of metastasis, which is which is ultimately one of the biggest challenges in cancer. How do you stop a cell from spreading through the body? Um, because, you know, if you have a localized group of of neoplastic cells that have not yet spread, either surgical debulking or a radiation approach could cure that that kind of a a condition. It's when the cells begin to spread, uh, that we have this bigger problem. And uh, we, we now know that that all metastatic cells have characteristics of macrophages, a mesenchymal kind of cell, dependent on glucose and glutamine for for survival. So, we have a pretty clear idea of how to how to kill metastatic cancer cells uh, using metabolic therapies, which are combinations of hyperbaric oxygen, targeting simultaneously targeting glucose and glutamine. Unfortunately, the field doesn't doesn't recognize that. And one of the great tragedies in my mind is is that the approach to try to stop metastatic cancer um, about almost 50% of the people treated uh, are being are killed from the treatments rather than the cancer. Um, which is another tragedy when we clearly know, based on work of Dom's and our work together, that these metastatic cells are remarkably dependent on glucose and glutamine, and and they can't, they can't metabolize ketone bodies uh, or fatty acids effectively, and now become extremely, extremely vulnerable um, to hyperbaric oxygen, if you can put the patient in nutritional ketosis, and then again, with low doses of glutamine targeting drugs and glucose targeting drug drugs like 2Dox, um, we, we can annihilate these tumor cells and keep the normal body super healthy. Um, and this is one of the great um, important issues in cancer, is how do you, how do you selectively kill spreading tumors while enhancing the health and vitality of the normal cells in the body? And Dom and I have worked out a lot of this. Uh, it's just the challenge of trying to convince people that this is the way it is has been harder than actually knowing how to kill cancer cells. It's just the field is resistant to it. More, more than the the field is more resistant than the tumor cells. Can you believe this? [laughter]

>> I, I think too, what the idea that Dr. Seed was advancing, like when I first read cancer is a metabolic disease. Uh, I really appreciated it from the perspective of being a physiologist. So, I was trained as a neuroscientist, but also uh, I, I was trained to understand the neural control of physiological regulation or autonomic regulation. So, I was trained as a physiologist, but then had to take neuroscience classes too. So, I, you know, I appreciated and understood that when you change your metabolic physiology, you are changing the fuel that you're running on. So, you are dramatically enhancing and upregulating fatty acid, fat metabolism and ketone metabolism, and really suppressing the hormone insulin. So, it's, it's more than just ketones and glucose and ketones and hyperbaric oxygen. So, I also think of, you know, a well-formulated ketogenic diet or ketone metabolic therapy, which includes uh, ketone supplementation that does not increase insulin. I, I think about it as insulin suppression therapy. And that by suppressing the hormone insulin, you're suppressing glycolysis. You're limiting glucose availability to the tumor. You're elevating ketones, uh, a fuel that the cancer cells can't use effectively for energy. And then in that context, uh, cancer cells have dramatically upregulated oxidative stress, and you're simultaneously inhibiting some of the endogenous antioxidant mechanisms. So, the cancer cells are selectively vulnerable to oxidative stress. And you know, we know the efficacy of radiation therapy is proportional to the partial pressure of oxygen of the tumor, and we know that hyperbaric oxygen reverses tumor hypoxia, and it also sort of decreases the the lactate in the micro environment, and that acidified micro environment really, really makes the tumor resistant to uh, standard of care therapies. So, I mean, at the time, before reaching out to Dr. See for the mafet was kind of interested in this idea of enhancing, you know, their therapies with hyperbaric oxygen because of the radiation therapy and things like that. And now the interest too is uh, enhancing hyperoxygenation enhances T-cell metabolism and infiltration, and also reduces uh, PD PDL1 expression and enhances also checkpoint inhibitor therapy. So, uh, right now, the mafet actually has a ketogenic diet trial on CARTT therapy. So, there's been an interest, and I think it was mostly spearheaded by Dr. Seafruit because of the work he's putting out, and other people now looking at ketogenic therapies to enhance the adaptive immune system to work to make, you know, standard of care therapies that are emerging work better. And that's super I'm interested in that area too. But I'm mostly interested in, you know, developing a comprehensive, non-toxic, metabolic-based, oxidative stress-based therapy for these cancers. And I think that's the, I'm kind, I feel like I'm working in kind of two different fields where I'm sort of, you know, embracing the idea of using this as standard of care. And I know Dr. Seafford has some thoughts on that. But at the same time, I think my passion is really to to work with a team to to advance the the use, the the development and the application, moving the science to human application of non-toxic metabolic oxidative stress therapies.

>> Yeah. Yeah. That's really good. Getting getting back to what you raised there, which was the acidification of the micro environment preventing many standards of care from working, which includes radiation, chemotherapy, as well as the checkpoint inhibitors and potentially CAR T immunotherapy. All all of these approaches have been recognized to be uh, less effective or poorly effective because of the acidification uh, of the cancer micro environment. And the acidification is primarily coming from the waste products of the fermentation metabolism that is that is driving the disregulated cell growth, and that being lactic acid. And uh, what we have shown, and what what we've shown is suinic, suinic acid. Uh, suxinic acid is the end waste product of the glutaminolysis pathway. Um, the tumors need um, um, uh, we, we have now provided the strongest evidence that the amino acid glutamine is actually fermented uh, in the mitochondria of the tumor. Um, and then suxinic acid, the end product of the glutaminolysis pathway, is dumped out along with lactic acid. So, uh, and and glutamate is another excitatory amino acid that's also dumped out. It's vented out from glutamine. So, so this is creating an acidic micro environment. The waste products of the fermentation driving the disregulated growth creates the acidification. So, if you simultaneously restrict glucose through nutritional ketosis, and then you use glutamine targeting drugs, pulsed, rather than pressed, because the immune system is uses the same fuel, glutamine. So, it becomes essential to understand how the immune system and the tumor systems are both uh, both using a common fuel, and we have to then uh, uh, do a strategy so that to maintain the health of the immune system, while while slowly degrading um, uh, tumors and and and and removing the acidification of the micro environment, allowing allowing some of these other therapies to come in at ex much much lower dosages, which make, once the tumor cells are are restricted of their fermentable fuels, and the micro environment becomes less acidified, you don't need much radiation. You don't need, you need very little immune therapies. You need very little of this, because the tumor cells now become super, super vulnerable to the lowest doses. So, overall, it's a win-win situation uh, for the patient in many, many different ways, and for and for the attending physicians, because you'll be able to manage these cancers so much more effectively. Uh, this is not being currently done. Um, we're, we're, we're giving patients high doses of immune therapies and toxic chemo and all this other stuff, trying to break through the acidification, when we clearly know how to stop the acidification. Um, and so this, this will move. So, eventually, you'll have a a hybrid system where the cancer cells, the patient is placed into a state of nutritional ketosis. One of the one of the hang-ups about the field is the term diet, ketogenic diet. Ketogenic diet is very ambiguous. What, what's more important is the state of nutritional ketosis, which can be enhanced by ketone supplementations, and and various various nutritional strategies, that will bring lower glucose and elevated ketones. And this can be done with pescatarian diets, carnivore diets, um, all all kinds of um, diets. And it could be uh, strategized per person, as very, very specialized for gender differences, cultural differences, religious differences. As long as the patient can get into a low glucose ketone index, which is what we've defined as being in nutritional ketosis, having a low GKI, five or below, to kill cancer cells, you need to go a little bit further below that. And then you come in, uh, you reduce the acidification. Uh, you can come in with oxygen. Oh, oxygen. Beautiful oxygen therapy works so much better on the patients. And then and then you can strategize uh, which immunotherapy, which member of the standard of care can then be brought in to finish off surviving tumor cells, because the ones that survive uh, the metabolic therapy will all have something in common, having survived this. Therefore, an epitope on the surface of these cells uh, could make these cells remarkably vulnerable to a more, another, another strategy. So, we, we all, as I've said many times in these in these podcasts, we already have all of the tools in the tool chest to effectively manage cancer with minimal to no toxicity. It's just that we're not using the tools appropriately, the ones that we have. We have to redesign how we treat patients from the very beginning, and how we transition them from one stage to the next, bringing in all of the different uh, uh, tools that we have, which is hyperbaric oxygen, which is ketone supplementation, which is simultaneous targeting of glucose and glutamine, and then and then monitor the patient as how they're going through the system. Many of these people start getting super healthy. Uh, many of these people that had diabetes and high blood pressure and hypertension along with cancer, all of those other things start to disappear along with the tumors. And as we said in the press pulse strategies that Dom and I wrote, um, we take patients from a very diseased state, and then we gradually move them into a managed state, and with further improvements in doses, timing, and scheduling, we could potentially bring them into the resolution state. Uh, and and this is this is the goal of press pulse therapeutic strategy, taking all of the tools that we have developed and knowing the mechanisms by which they work, and bringing them all together in a synergistic interaction to allow these patients to survive much longer with a higher quality of life.

>> Yeah. And and it's, it's important to appreciate its many mechanisms kind of working in synergy too. Uh, and with nutritional ketosis or ketone metabolic therapy, I mean, that could be implemented with a calorie-restricted ketogenic diet. If the patient's underweight, euhcaloric diet, if they're overweight, you could do significant calorie restriction. You could do therapeutic fasting to set them off and to quickly get them into ketosis. And then we have focused a lot of attention and work on developing ketone supplementation, uh, that is remarkably effective at lowering the glucose ketone index. And I think there's different types of ketone formulations that have a greater anti-cancer effect, that some of the esters will increase insulin. So, you want to develop something like a a buffered electrolyte DL beta hydroxybutyrate that is more effective. It does has no effect on insulin, but has some anti-cancer effects to that. There has been quite a bit of pushback on ketogenic diets primarily because of the high fat content of the diet. But if it's calorie restricted, >> yeah, >> you know, or even euhcaloric, there's no basically every cardio, I like to say cardioimmuno neuromabolic biomarker, because what's healthy for the heart is healthy for the brain, and also enhances uh, the immune system in ways that has an anti-cancer effect. Every cardiometabolic, you know, biomarker is going to improve. Uh, there's one biomarker that mainstream medicine has a myopic focus on, even a manic focus on, and that's LDL cholesterol. >> Primarily because we don't have to go too much into it, we have drugs that lower LDL cholesterol, and a, so there's a, you know, some doctors will push back on the the high elevation in some patients, you know, of the LDL cholesterol. Um, I've consistently seen in cancer patients that LDL drops as their cancer progresses, and I think there's reasons kind of for that. But like low LDL is associated with faster cancer progression. Um, so maybe there's an opportunity to use statins too, because, you know, cholesterol is used for the biosynthesis of tumors. But I think the push back on ketogenic diets is not really founded in, you know, good understanding of metabolic physiology, and, you know, I think it does more harm than good, especially in the context of like a GBM patient. So, if they're getting push back from their doctor on that, u, and we just have such good data that these diets in the context of standard of care being completely ineffective or refractory, in the context of ketone metabolic therapy and other things that we're talking about, we could make those therapies dramatically effective and reduce the side effect and reduce the dosages. So, uh, so I, I do think about this as an adjuvant in that setting, but ultimately, I think the future is coming up with a comprehensive metabolic-based approach that that could ultimately replace the standard of care, which is archaic. Not that I mean, there's some immune-based therapies that work great for multiple myeloma, lymphoma, and other uh, types of cancers. And I think they are lifesaving, and I know quite a few people. But for advanced metastatic cancer, brain tumors, and a number of cancers that um, you know, I think a metabolic-based approach should be embraced and utilized in a way, and then the standard of care approaches that are being used now could be used later, if if they need to be, you know, after monitoring the patient. I think that's uh, if we're talking about quality of life and really ultimately the patient's survival.

>> Yeah. >> Well, you know, Dom, I think you're right. Um, getting back to the cholesterol and and these kinds of things. Um, those problems happen when the when the when the therapeutic ketosis strategy is not done correctly. We, we always emphasize calorie restriction. Um, no one should go out uh, and eat a tub of lard, thinking that that's going to help their their situation. But there's so much misinformation in the diet world from ketogenic diets are so unhealthy because they're full of fat. But you, you can do a calorie-restricted carnivore diet. You can do a calorie-restricted pescatarian or even a a Mediterranean diet, as long as it's restricted, and blood glucose goes down and ketones go up, measured by the glucose ketone index calculator. And and when you're on the right path, the best, a good blood marker in my mind is triglycerides. But we, we see when you're when you're in ketosis, nutritional ketosis, your triglycerides are down, which is one of the one of the key biomarkers for cardiovascular health. You keep your triglycerides down. I'm not as concerned about the cholesterol issue as I am about the triglyceride issues. Uh, and if you're on a low, if your triglycerides are dropping, your blood sugar is going down, your insulin levels uh, are going down, your ketones are going up, you generally enter into the state of nutritional ketosis, which is exactly pretty much the same as all of our ancestors during the Paleolithic period of our existence as a species. We were all in a state of nutritional ketosis because we didn't have, as as Bud Vich used to say, we didn't have delicatessens or doughnut shops on every corner. So, our ancestors were were were always in some state of nutritional care. They had a lot of exercise, very few carbs, a lot of meat. They were generally devoid of the chronic diseases that are crippling uh, the world population today. And we know this pretty much because if we look at tribes like uh, Albert Schweitzer had done, looking at the how how ancient tribes that followed their traditional ways, a lot of the chronic diseases that are plaguing us today were not even known or seen in in many of these tribes. So, they were living in a state of nutritional ketosis, a lot of exercise, a lot of natural organic foods, all organic, as a matter of fact, and and they h they did not have chronic diseases. Um, yes, our ancestors did not did not have um, they died predominantly from injuries and infections, mainly because we didn't have antibiotics, we didn't have orthopedic surgeons, and we didn't, we, we didn't have a lot of the things that we have today. But they were not dying from chronic disease. Today, we are riddled with all kinds of chronic diseases, cancer being the number one in that regard. And we, we are just trying to use our understanding of metabolic therapies to bring the body back uh, to the way it should be, a state of nutritional ketosis, a, and and in managing uh, a very aggressive disease that we think can be managed more effectively. And yes, it will be the combined synergies uh, of all of the different tools that we have. Uh, and I, and I agree with I agree with that. But again, there's so much misinformation about ketogenic diets being harmful, and uh, and none of these are done the right way. If you do it the right way, it's always almost always very therapeutic. And when you see arguments that say, "Oh, these patients didn't do well." They never went into a low GKI in the first place. They, they had other issues that were standing in the way. They weren't imple, they were eating ad libitum or unrestricted amounts of of fats and things like this, which are very unhealthy. So, we need good nutritionists and dieticians who also understand the concepts of what Dom and I are talking about, so they can guide their patients through uh, through the strategies, through through the requirements of of what they'll need to do to bring themselves back to u, what we call metabolic homeostasis. And this is an extremely important concept, metabolic homeostasis. Uh, when you have chronic diseases, your body is not in homeostasis. You're out, you're out of balance. You're metabolically out of balance. What nutritional therapeutic ketosis does is bring you back into a state of metabolic homeostasis, where cancer cells and other other issues associated with chronic diseases become less and less problematic and eventually will disappear. We can cure type 2 diabetes with metabolic therapies. You can get rid of hypertension. Uh, uh, you, a lot of neuro psychiatric problems uh, that are afflicting people can be managed with nutritional ketosis. So, and we're using the GKI as simply a quantitative biomarker to allow people to know what does it mean to be in nutritional ketosis? What do I have to do? How do I know I'm there? Well, you have a glucose ketone index uh, marker that we are developing as a tool to allow people to know what stage they're in. And then uh, whatever disease you might have, whether it's cardiovascular disease, or or cancer, or one of these others, even dementia, uh, it most dementias are the result of metabolic in homeostasis, uh, um, bad diets and lifestyles that are putting pressure on, and all of it eventually comes down to mitochondrial health. That's ultimately what we're dealing with here. Uh, mitochondrial dysfunction is the underlying uh, pathological process uh, of all of these different chronic diseases, including cancer. Cancer is a mitochondrial metabolic disorder. Otto Warberg was the first to define cancer as a metabolic disease. The field went off the track thinking that it was a genetic disorder. We have now accumulated enough information to show that cancer cannot be a genetic disease. It's a mitochondrial metabolic disease. So, we must view it as that, and then develop strategies and approaches knowing that, and the outcomes on patients' overall health, the reduction of chronic diseases in the country and throughout the world will happen uh, once once people come to realize uh, what do and I are talking about here.

>> And I just want to add, like, I think there's like four things that you really need to pay attention to when a patient transitions to ketone metabolic therapy. And I think there's biomarkers, and that's a whole discussion. I've given talks on that. But just the cardio metabolic biomarkers, glucose, ketones, insulin, HCRP, triglycerides. HCRP is actually a better cardiovascular risk factor to monitor than LDL cholesterol, like the hazard ratio, it's like higher.

>> Okay. What, what how do you define HSRP?

>> High sensitivity, high sensitivity C-reactive protein. So, yeah, high sensitivity C-reactive. So, mine trended to be high, and now it's like, it's non-detectable or 0.1 or 0.2 since I've been in ketosis. So, that has.

>> Why, why you're always in ketosis or almost? How is it possible that you could even have a C-reactive protein elevation?

>> Oh, well, that's just like your normal. So, I have been elevated. My C-reactive protein has been elevated two times. One, I lived underwater for 10 days in a NASA analog, and I came up and I was breathing, you know, 4,000 parts per million of CO2 for a while, and under a lot of stress. And another time >> I came back from Southeast Asia and I had a gut bug, and I had some intestinal permeability that boom, that triggers an immune response. So.

>> Your immune response is good. I mean, it keeps you. It's.

>> Uh, HSCP is an indicator that your immune system is activated. So, you see it with, you know, age-related chronic diseases and autoimmune diseases. Uh, but when someone goes on ketone metabolic therapy, there are biomarkers that need to be monitored.

>> You want to uh, you want to ensure they're not losing strength. If they're losing strength, they're losing muscle, and just their overall vitality, right? So, there, you want to monitor. I'm a big advocate of like, ensuring muscle strength. They should be getting a DEXA scan like over time, once a year at least, or once every, if they, because it's easy to lose muscle if you calorie restrict too much. And subjectively, you want to make sure the patient feels good on a ketogenic diet. So, they need to be coached. And we know that ketone metabolic therapy can have a tremendous uh, impact on mental health. It, there's a whole field that has developed, spearheaded by uh, the Bazooki group, on metabolic psychiatry. And I think when a cancer patient is diagnosed with cancer, when they get chemotherapy and things like that, they have a, they get anxiety, they get depression, and this increases exponentially. So, I think one area of research that we need to like focus on is actually improving the mental health of patients that have cancer. And one effective way to do that is another, I don't want to call it, you know, make it sound like a panacea, but when you're in a state of nutritional ketosis and you maintain that, it has an anxiolytic effect. It actually can decrease symptoms of major depression. Dr. Jeff Bolick just published on that. It could target, it could help with bipolar, schizophrenia, uh, and also, you know, a wide variety of anxiety disorders. So, I think this is another sort of feather in the cap or ketogenic.

>> Well, well, sure. And and if you're treating your patients initially, cancer patients with nutritional ketosis upfront with a press pulse therapy that we developed, the probability of them getting into a neuro psychiatric problem would be reduced in the first place, >> because you wouldn't be, you'd be lowering the the drugs that would be initiating these kinds of uh, neuro psychiatric problems. So, so clearly, all of these aspects, we have a strategy uh, that can mitigate many of many of the issues that cancer patients are are are dealing with. The the the the biggest, I I would say, a a very large problem is getting this information into the clinics. Um, when you talk to oncologists, they have never heard of almost anything you and I have just discussed. Um, the the discussion is not even, uh, mentioned. It's not, medical students in the medical schools are not getting any information uh, about managing chronic diseases using metabolic therapies. Yet, chronic disease represents the single biggest drain of healthcare uh, costs in in the world. And and um, uh, you know, everybody's yelling and screaming about healthcare budgets and all this. Most of it's for managing chronic diseases. A and and we have a clear plan and a strategy for managing cancer and all these different chronic diseases. But the information is either not known or misunderstood or, and I think I think the, there's a massive educational mission that needs to accompany what you and I have been discussing and studying for quite some time. And I'm not sure how we do that, Dom. What, what are our strategies for doing that?

>> Well, it's true. Oncologists are not formally trained in it, but I'll say no less than three oncologists have reached out to me for guidance because they personally got diagnosed with cancer. >> So, they, they are from the field, and they are just seeking information, and they're just finding what they can find online uh, for three different types of can. So, you know, I think uh, you know, mainstream oncology and academic institutions that have cancer research programs, they're very interested in enhancing their standard of care. So, I've kind of, you know, been working in that domain. I think there's a lot of potential there. But I think to move this and advance the science into human application, uh, we really do do need federal funding, state funding, probably philanthropic support, most likely maybe industry funding, too. I'm not against industry. I, I think we should get funding wherever we can get it to just advance, you know, the concepts here. And it's, it can be very daunting and overwhelming, everything that we're talking about. But at the very least, ketone metabolic therapy is achieving and maintaining a glucose ketone index of like one to two or one to four, I think. And there's a straightforward way to go about approaching that. And then there's many different add-on drugs and things that you could do in addition.

>> What, what, what do you, what do you think your GKI is today?

>> Oh, I just measured it. So, I have [laughter] uh, I have Oh, I GKI, right? I got the the keto mojo right here. You can see there's still blood on the strip here. [laughter] So.

>> But so I'm testing it. I'm actually have various experimental agents here that I'm testing. If.

>> Yeah. >> If you consume this, you would this would kill five people into keto acidosis. It's a very.

>> Well, you always had those kinds of things. But we, we had a test here in the lab uh, a couple of months ago where we, we were going down into uh, to test what we needed to do on a carnivore. So, so when I went out and I, I bought some nice ribeye steaks and filet mignons with sauce and this kind of stuff. And uh, after four, I, I started off, I was about 50. Uh, which, which is um, I think it was late high 40s, 50. Um, and and then after about uh, five days, I, I was down to a 10. Um, I got down to a 10. But if I had taken, and one of the guys in the lab, GKI, a GKI of 10, >> okay, >> going from 48 to a 10. But one of Dr. Dur in the lab had consumed some of your, we were all supposed to be uh, doing our whatever we need, but he chugged some of your ketone solution, and and he got down, down below below two. He was down like 1.5. So, so, uh, he kind of cheated on the group, um, because we were all supposed to see what a what a carnivore diet would do. But if you, I'll tell you another thing. If you exercise when you're on these diets, you get down, you get down into these low zones uh, uh, really fast. The the question that we have for people is how you maintain to stay in the, in the longer you stay in those in those zones, uh, the more pressure you're putting on cancer cells, and the healthier your normal cells in the body, the brain, everything is getting. Um, so the strategy is not only getting to the zone, but also maintaining yourself in the zone. And we know that people will fall out of the zone periodically. How long does it take to get back into the zone after you go out and eat a pizza, uh, or or a big donut? And then you have to bring your body back into that zone again, because you can't, we can't allow people to feel uh, terribly depressed because they're not enjoying uh, their life, what we have in our society. So, this all becomes the diet and lifestyle issue. Um, I don't know if everybody everybody is as disciplined as you are. Uh, but most people aren't there. And and you have to stay in those zones, and you have to have a strategy to allow people to enjoy a party. Well, of course, if you have a deadly cancer, you might want to. But I'm talking about for prevention of cancer, because because you, it's hard to get cancer if your mitochondria are healthy. We have never found a person with cancer having a healthy mitochondria. They're always dysfunctional in some way, especially for oxidative phosphorylation. So, prevention of cancer and chronic diseases means that you should always be monitoring your GKI. Knowing you don't really have to stay solo. If you were to have cancer, you better get down into those low zones to kill the tumor cells. But this knowing right now, there's a lack of knowledge on what to do and how to do it, and and you and others will define strategies to help these people remain in these zones. What, what level, what level of flexibility do you have in your diet and lifestyle to pop out of the zone and get back into it, in different ways? Maybe a ketone supplementation and exercise would bring you back into the zone. See, this is the cutting edge. Um, we know what we need to do. Uh, we know how to get there, but we need to know what is the best way to maintain for whatever you for whatever you're dealing with. Are you dealing with, you just want to prevent yourself from ever getting cancer or a chronic disease? Or now that you have a chronic disease or cancer, what is the best way that I can stay in the zone? What is the best way that I can feel that I'm I'm I'm working to resolve the problem that I have, and I'm doing the the thing that it's nice about nutritional ketosis is a lot of the effort falls on the shoulders of the individual. You don't have to be allowing a a a system that is failing in managing cancer and some of these other diseases. You now have charge of your destiny because you now understand this. But they also need instructions, and they need assistance, and they need guidance from people like yourself and others that can help these folks, because because it does become a real challenge, and I think this is this is some of the areas that we need to we need to focus on as well. In regard to implementation, you need to set guardrails. So, you need an accountability partner. I think that's going to be important. You can't, it's hard for one person to do ketone metabolic therapy if everybody else in the household's eating, you know, right processed food. So, you could use, for example, a continuous glucose monitor, >> and then set the parameters that when it pops up above a certain threshold for glucose, that it, it, you know, gives an alarm. And you know that we know that in in research, if we have subjects wear a continuous glucose monitor, we can unambiguously monitor their adherence to a ketogenic diet, because their glucose is not going to spike. >> Right. So, I think, and there like in the fitness world, you know, on the weekends or whatever, you know, it's, it's pretty common for people to just prepare all their food for the week, and then set all their meals aside. This is what I'm going to eat for the week. And I think that sort of strategy could be adopted by the cancer patient. Alternatively, there are food companies out there. Trifecta is one of them. Uh, I

I think I've had conversations with that they will just send you. You can allocart. You could pick low carb, you could pick keto, or whatever. They'll send you a whole week of food, uh, to your house on your doorstep, and you could eat that. And I think, you know, that could be maybe affordable for some people, but maybe not all people. But I think everybody can, everybody can eat. And you could just go, whatever is on your grocery list and whatever you have in your house, that's what you're going to eat.

So, if you're following a ketogenic diet, you have to ensure that when you go and buy food, that you, your food list includes foods that are, you know, uh, in line with a ketogenic diet meal plan, and that you have that. And you, you know, >> well, as you said, >> as you said, if you're monitoring, if you have a continuous glucose or better yet, a continuous glucose ketone monitor, >> so you don't have to prick your finger, uh, to do a keto mojo. Uh, you and you have these, um, zones that you said would these, what you call them? >> Uh, >> yeah, I mean, you could do >> warnings. You have a warning. Um, >> yeah, you could do time and range too. >> Time and range. Absolutely. This is exciting. So, so people, people will know, uh, when they eat something like what you might eat, what I might eat, what Morgan may eat, may elicit a different GKI. Um, so each person will have to know what, what arrangements of foods and, and, uh, selections would be optimal for their particular, uh, state of ketosis. Um, and that, as I said, that could vary, but your age, your gender, all of these things could make a difference. And, and everybody will have to be using them themselves as a guinea pig to know at what zone of the GKI they find themselves, uh, that produces a range most efficient for their, for their body.

So, this then, um, again, it's an experiment. Right? Now, you see, without that knowledge, people are guessing what they are, unless they do the mon from a keto mojo or something like this, uh, they're primarily guessing. And, and, oh, I'm in keto. How do you know? Well, I've been eating avocados all day. Yeah. Well, what's your GKI? Well, I, I don't know. I never measured it. So, so again, once, once the fac, once it becomes easy to measure the GKI with a variety of different approaches, I think we're going to start to shift, uh, and reduce all kinds of chronic diseases because people will know what to do and how to do it. And right now, we have that gap in, uh, in, in utilization of all this. So, I'm looking for, I think this is a very, uh, fruitful area. I, I think this is the future. Um, we know, we have a chronic, even RFK Jr. said we have a chronic disease issue. He's not wrong about that. We do. Uh, and, and, and you and I and others, we have a strategy to manage that. Uh, and, and, and, and we, the ones who know, we are the ones that understand the mechanisms and how to do this, I think, better than anyone else does. So, so, um, because we, you and I have had the longest exposure to this stuff, and we've been thinking about it for a long time, and we've been designing experiments to test all this, and it's not yet perfected, but it's certainly on the right path, uh, for, uh, for, for a deliverable, uh, solution to the chronic disease problem, including cancer, and, and I'm excited about it.

>> Yeah. And 20 years ago, there was like no cancer metabolism conferences. So now you have like keynote conferences. Now you have like major cancer societies and organizations have like cancer metabolism like conferences and stuff. They, they approach it from maybe a different perspective from, you know, a lot of people in, you know, cancer oncology are molecular, are geneticists or molecular biologists, and maybe they don't have an appreciation for metabolic physiology. And I think that's, that is important because you change your physiology, you change the tumor microenvironment, >> oh yeah, >> in a way that, you know, suppresses cancer. And, >> you know, at this point, we do not have a cure for cancer, but we have really, we have evidence-based research and mechanisms that we can, uh, you know, target with ketone metabolic therapies. And we also know that, you know, there's an, we know now that in regard to modifiable ways to prevent cancer, if you look at 12 of them, and a recent review came out maybe about a year or two ago by, um, do you know that cancer journal? It's like the flagship journal of the American Cancer Foundation. It's a, it's an impact factor of 500. I didn't even know that was possible, Tom. Yeah. >> Journal of the National Cancer Institute. >> Yeah. It's, it's their flagship journal and it was, and they, >> they me, it's a, it's an actually an impact factor of 500, which I didn't know I had to fact check, >> existed. Yeah. >> It's the highest impact journal. So they published an article on, uh, modifiable risk factors for cancer. And, uh, and, and of the 12, I would say eight or nine of them were directly related to metabolic health, right? Like obesity, like smoking was the top, but that's going to be replaced by like obesity. It's like, you know, high blood glucose, inflammation, like all these different things. Uh, and then the ones at the bottom, maybe that were not included were some things like, uh, maybe H. pylori or different, like Epstein-Barr virus and things like that. But, but I also think that ketone metabolic therapies can be used to augment the immune system, >> uh, and even change the, the microbiome, for example, to even target things like H. pylori or to enhance your immune system in a way to prevent some of these viruses from having oncogenic, uh, effects, like in the body. So I think, you know, adopting this way, I'm very interested in basically protocols that people could do for five days or maybe a week once every month or three months that could put themselves into a state of, you know, therapeutic ketosis for a predetermined time frame and work. Valter Longo showed that you have lasting effects from that, you know, two, three weeks, even months, if you can achieve and maintain a glucose ketone index, which would be equivalent based on his research between like one and four. And you do that, you know, five days out of every month or two, and I think that can actually produce long-term changes in various biomarkers that would correlate with prevention of cancer.

>> Yeah. Well, you know, we, we did some studies years ago with the mice when we fasted them. Now, a mouse, a mouse with a 40% calorie restriction is like a water-only fast for humans. And, uh, uh, like a 7-day water-only fast for a 40% restriction. And then when we refed the animals, um, they were, they were eating less food, uh, but maintaining the constant body weight that they had, which means that their entire physiology has been, uh, made more efficient. Um, body weight is a critical variable to know how, how your body is, overall physiological state. So these animals were eating, um, 8% less food than they did before they had the, the therapeutic fasting, and yet maintaining this, the same body weight. So, so clearly, the energy efficiency, they, they were, they were more energy efficient in what they were doing. This could possibly explain what Longo was saying, that your body has, has learned, uh, to become more energy efficient. Um, the problem, >> dieting tomorrow. Yeah. >> Yeah. Yeah. Yeah. But the problem with that is, of course, is if you're eating a high carbohydrate meal, you're going to gain, you're going to gain weight a lot faster after, after doing something like this. So, uh, but again, these are the issues. Once you understand, uh, this, then, then you can develop approaches to, to, uh, to deal with it. And right now, everything seems to be for a lot of people, a mystery. They don't understand this, and they don't understand that. But, but with respect to the drop in cancer deaths, the biggest was the anti-smoking campaigns from the 1990s. Not any new development in drugs. There's been very, the cancer has increased consistently. Um, and I get a little peeved when I hear people say that, oh, we've made enormous progress in cancer, or the progress was the anti-smoking campaign predominantly. Very none of these new drugs are having any major effect on dropping death rates. And that's because they're think that cancer is a genetic disease. All of the new drugs are being developed, they're all based on the molecular biology of cancer, which is a genetic problem. And if it's a mitochondrial metabolic problem, uh, you're never going to get a, a reduction in, in death rate. Once you realize that you, that this is a mitochondrial metabolic problem, uh, it explains why the anti-smoking campaign was so effective, and you can then institute and get real reductions. You can get real reductions in the, in, in dropping the death rate. But a constantly approving EGFR receptor immunotherapies or all this other stuff, uh, this is not going to, um, make any major differences. Um, the other thing too is, I, I agree with you. I never use the term, I never, I try never to use the term cure. What we're interested in is management. And I, I think if, if survivability for a particular deadly cancer like glioblastoma or pancreatic cancer or advanced lung cancer, I, if you can triple or quadruple the months of survival in a higher state of quality of life, I consider that success. If you can make glioblastoma a five-year survival, the norm rather than the exception, I consider that success. Um, so, so you're giving people an opportunity to live on the planet with a higher quality of life, far greater than anything that's currently being done. I consider that success. So, if the management runs long, and you die from old age, uh, from something other than cancer that you had when you were in your 30s or 40s, then you were cured. But we don't know because at any time, under a certain circumstance, cancer could come back again. And, and then you say, "Well, you didn't cure me." Well, we never were, the design was never to cure. It was to manage. And if the management lasts long enough, then you can say you were cured. But I, I think we should always look for successful management. And what does that mean? It means a high quality of life with no evidence of disease. Um, in the case of Pablo Kelly, who lasted 10 years with a glioblastoma, it never went away. He was just managing it with metabolic therapy. He had four debulking surgeries and died from a cerebral hemorrhage on the last, on the last surgery. He never died from the glioblastoma. He died from, from a surgical problem. So he lived 10 years, had two children, got married, he had married and two children. That's what I call success because had he gone standard of care, he would have been dead within, uh, a year or, or 12 months, like, like the physicians told him. So, so I consider him a success. But I consider so many other people a success. They're living longer with a higher quality of life because they've done metabolic therapy. And you and I are perfecting this. So the managements can be pushed and pushed and pushed far into the future, which is success. And this, this level of success is far greater than what's currently being done with standards of care, which, as I said, so many times are so toxic, uh, uh, based on an incorrect theory and incorrect or lack of understanding of the, of the very, uh, topics that you and I have been discussing.

>> Would it be all right if I jump in with a quick question? >> Yeah. >> Yeah. Because Dom and I can go on for hours. [laughter] >> That's perfectly fine. You've been, you've been going through all of your research together, which is exactly what we wanted. But based on all that great summary of your past research and how really ketogenic metabolic therapy can potentially become the new standard of care for cancer. I wanted to touch upon a very common audience question that you get, Dr. Safe-Freed, in your comments sections, where a lot of people ask, um, when they've heard about the press pulse protocol and KMT for the first time. The first question they ask is, are there any clinics or potentially clinical trial groups that are providing this guidance to patients? What would you both have to comment on that?

>> Well, I, I mean, I, I get that all the time from thousands, thousands of people who, who contact me. They get all excited. They hear what Dom and I are talking about, and then they go to their major clinics, um, whether it's MD Anderson or Dana Farber, Sloan Kettering, the Mayo Clinic, Fred Hutch, all of these different cancer centers. And a lot of the times the people, well, I never heard of it. Um, uh, what do you mean? Glucose has nothing to do with cancer. And the patients get very, uh, very disillusioned and feel, feel very bad. Sometimes they're met with hostility. But the, but the issue is, is why are there no clinics? Why, why are the top medical schools not entertaining, uh, what we're saying? And, and again, a lot of it has to do with the power of the, of the system. Uh, the system is based on large profits. Can the cancer industry is a multi-billion dollar industry, and, and I think, I think the, I, I hate to say it, but it's, it's revenue generation. Uh, how, how do you generate revenue, uh, to the same level as we're currently generating, uh, when you're using calorie-restricted ketogenic diets, ketone supplementation, exercise, uh, and a lot of the things that you and I, that Dom and I have been speaking about? It has not yet got into the mainstream, because it, it would be very unsettling to a lot of programs to, to have people wanting that as opposed to very expensive toxic therapies. Um, why, I think there are some more clinics opening up. We're starting a new, um, um, a new society of, of, of metabolic oncology, International Society of Metabolic Oncology, where Dom is a participant, as well as I, and many others. There are, is a growing, uh, awareness that that what we're speaking about will be very effective in managing cancer. Um, but we need more education. We need clinics that will allow us to do that. We have to have, uh, open-minded people in the IRBs, institutional review boards, who are interested more in patients than revenue generation. Um, and then, and then once you start having that, uh, you'll start to see a groundswell of interest and perfection, uh, of what we're talking about. But, but right now, that's a big, one of the biggest problems, as I was telling Dom, is that poor, these poor people, they have nowhere to go. Um, and, and we're doing the best we can to try to train people. Uh, and a lot of it's being done on Zoom and small clinics and, and, um, but it's, [snorts] should, it's not yet mainstream by, by, by, by any stretch of the imagination. So we need to get it out. We need to have people have this opportunity to be treated by knowledgeable physicians, people who know what Dom and I were speaking about, people who are able to integrate standards of care effectively into what we're talking about. Uh, we have some clinics opening up in Istanbul, Turkey. As a matter of fact, we were talking to a couple of folks the other day, MDs in their clinic, where they're, where they're, many of their, uh, stage 4 pancreatic cancer patients are living beyond five years doing metabolic therapy. Uh, we have to publish these papers as well. We have to let the, the scientific medical community know what was done and how these people are living so long, what was done. So again, it's an educational mission. It's a scientific mission. Um, but right now, it's a, that's one of the biggest problems. These poor folks have nowhere to go, uh, to get the stuff that, that Dom and I are talking about. Um, so, that, that has to change. And, and once it changes, then I think we're going to see a big drop in cancer and a lot of these other chronic diseases.

>> Yeah, I think the problem is multifactorial and kind of multi-dimensional in some ways. So, you know, they're going to ask, I mean, we really need systematic reviews and meta-analyses of the literature to show to convince people. So, that's going to require, you know, gold standard RCT therapies on these things to, uh, and it's not going to be done as a standalone. Typically, it's going to be done to augment. But you also have a lot of heterogeneity within, within the, the field of cancer, like the different types of cancer. So, but I think it's, it's most important to focus, uh, as Dr. Dr. Safe-Freed has done, on glioblastoma, because that's kind of like the, the therapy that if you can make some inroads into that, then we'll have kind of a basic understanding that, that cancers that are highly glycolytic, you know, that have this mitochondrial damage, and that, really are have the hallmark characteristic or phenotype of the Warburg effect, that they're going to be responsive to, to metabolic therapies. And you need cancer institutes do not even have on staff registered dietitians that are trained in understanding ketogenic therapies, unless it's for pediatric epilepsy or, or something like that. So there needs to be education into the power of nutrition, you know, in, in cancer, uh, in metabolic management of cancer. And, and there needs to be, uh, there needs to be guidelines for implementing this. And oncologists need to really expand the field of oncology needs to expand into met, you know, metabolic oncology. And even exercise is a very powerful tool. The research, Arch behind exercise and oncology is remarkable. So, uh, exercise oncology, so that could be, you know, another field. But I think of exercise also as a form of metabolic therapy. So even just a cancer patient implementing this could just do, you know, two, 20 to 30 minute brisk walks each day, you know, if they're able to do that, and that's going to have a tremendous effect. Uh, and it's just simple things that, that cancer patients can do. But when a cancer patient goes to a clinic, the standard of care happens to you. So with ketone metabolic therapy, what we're talking about here, the, the ketone metabolic therapy is implemented by the patient at, in their home. You know, ideally under the guidance of a trained registered dietitian who is has a background in, you know, implementing, uh, and advising, uh, and directing patients, because every patient is a unique metabolic entity, and they really need to be coached. And that's why I really emphasize, you know, biomarkers, looking at, you know, quantifying and measuring your body composition over time, looking at subjective things like your, your mental health and your energy levels, like all these things need to be taken into consider, consideration to get the best outcomes for cancer patients. Because otherwise, if it's implemented improperly, there, the potential for harm can exist if there's too much restriction, if there's, you know, diets that are not well formulated. Uh, and even with some of the off-label applications or off-label drugs, you know, they, they have the potential to do harm if they're not, uh, you know, utilized, uh, in a really strategic way, in a really, you know, >> uh, calculated way.

>> Yeah. Well, I, you know, Dom, I agree. Um, well, you're, we, I know we started with GBM, glioblastoma, only because they really don't have anything. There's been no advance in a hundred years for that, managing that, that cancer, and we have a clear strategy for keeping these people alive a lot longer. But I am not, I, I now, having having looked at in detail all the major cancers, uh, we have never found a cancer with a normal number, structure, and function of mitochondria or having a normal, uh, sufficient oxidative phosphorylation. Meaning that every major cancer will be susceptible to ketogenic metabolic therapy because every major cancer has the same pathological problem. They, they are dependent on a fermentation metabolism of glucose and glutamine. We have never found a cancer that can survive without glucose and glutamine. So that means lung, breast, colon, bladder. So, so, uh, I, I don't see cancer, I see it as a singular disease, not as multiple disease heterogeneity, only in the form of genetic mutations, uh, but not in the form of, of a metabolic, uh, problem. They all have, they all, all major cancers, we have looked. I just, in our new big paper on the, on the emergence of the mitochondrial metabolic theory and the Warburg hypothesis, we have found that all major cancers have an insufficiency of oxidative phosphorylation, requiring a dependency on substrate-level phosphorylation, which is a fermentation. Meaning that all the major cancers will be, uh, susceptible to management with ketogenic metabolic therapy. We just focused on GBM because they have nothing, but they really don't have anything for advanced lung or pancreatic cancer either. Um, but those cancers are remarkably susceptible to the same therapeutic. This is the, this is what's really important. All major cancers are a common disease of energy metabolism, and metabolic therapy targets that common pathological problem. Meaning that we have a strategy for managing all major cancers, and, and I, h, we have the scientific evidence to support, uh, what, what I'm saying. But I agree, I mean, we started with GBM because they're really desperate and, and lack of anything, but we can do the same thing for all the major cancers. Um, early stage cancers can be, can be stopped dead in their tracks. Um, so, so, uh, yeah, I'm, I'm, I'm, I'm excited about this. And I know it, it's very controversial to what the NIH says that cancer is a hundred different diseases. They say it's a genetic disease on their website. I mean, these are, this is all misinformation. That, that needs to be corrected. And, and, and the guys down there at NIH, uh, they better get their act together soon because the people are learning what's going on, and they better be consistent with the science. And if they're not consistent with the science, they're doing a great injustice to the American and the world population.

>> I have a question to follow up on that. I wanted to hear both of your opinions because you both briefly mentioned funding and the need for more funding for this kind of research. Based on both of your experience doing research in this field, is there or does there seem to be a bias in organizations like the NIH who provide grant funding for this type of research if it doesn't involve a drug or a treatment?

>> Well, you know, it's not necessarily a drug or a treatment. It's the theory under which we view the disease. If, if, if cancer is considered a genetic disease, and you're coming in with something that's unrelated or different from that, uh, then you have to, real, you're not going to get funded. And, and who are the people sitting on the study sections in, in at the NIH who award the grant? They're ultimately the people who make decisions. And if you, if you're saying that, you know, we're studying a way to manage cancer that does not involve targeting genes or sequencing genes or doing this kind of thing, um, the, the enthusiasm is much less than if you're doing what mainstream thinks is to be done. This is why the paradigm shift has to happen. It, it's not a genetic disease. Um, and, and people who think it is are, are standing in the way of progress. And the majority of the NIH National Cancer Institute thinks cancer is a genetic disease. So you're dealing with a very foundational resistance because the theory is what we're talking about is a different kind of a theory for the disease. It's a mitochondrial metabolic disorder. It's not a genetic disorder. The evidence is so overwhelming against that theory that you have to be living in the dark ages not to see it. So, so that has to change. Once that changes, then there's going to be a groundswell of funding and interest in what we're talking about. But that time is not today.

>> The idea I just want to put out there because there's also epigenetic regulation, and the metabolic control of epigenetic regulation can be pretty profound. So these metabolites in circulation not only function as, you know, in, in energy and, and, and in, you know, growth and things like that, but these metabolites, lactate and beta-hydroxybutyrate, for example, there's, there's a field called, you know, a process called beta-hydroxybutyrylation, where the beta-hydroxybutyrate can directly interact with the histone and cause histone modifications that can activate, uh, gene programs that have an anti-cancer effect. So I think if the field, I think the field can embrace this idea of altering metabolic physiology with ketone metabolic therapies to actually produce an epigenetic effect. We know that ketones have, can, uh, function as histone deacetylase inhibitors, and, and, you know, there's a whole anti-cancer drug class with histone deacetylase inhibition. So, um, so I, I have, uh, an outlook perspective that I, I think the field can sort of mesh. People on the genetics and metabolism can kind of converge on epigenetic modulation, and there could be some crosstalk to advance some of these metabolic therapies and maybe, uh, re, re-package them as metabolic epigenetic therapies. Because there's a dynamic interaction between the metabolic control of epigenetic regulation and also immune regulation. So our gut microbiome, for example, is profoundly changed with dietary therapies and metabolic therapies. And, uh, and there's various, uh, things like you can, you can expand the, the CAR-T therapy, you can expand T cells with, and beta-hydroxybutyrate plays a big role at sort of expanding the, the T-cells. So that's why Mayo Clinic is looking at CAR-T therapy and ketone metabolic therapy. So, I, I think, I'm hopeful that the field will sort of go into the direction and, and think about these ketone metabolic therapies as, uh, in more advanced terms. And I think there's a lot to unpack and understand in regard to, you know, even delving into the multi-omics, the transcriptomics, the even metabolomics, because I think these things are, it's kind of simple, it could be packaged in a simple way for the patient, but I think there's a lot for the scientist to unpack in how these things, and even personalizing therapies too, using some of these advanced tools that are already being used in, in oncology. And that could be, you know, big NIH, uh, grant program project grants. I had, uh, an email this week from Casey DeSantis from the state level. They were specifically asking for proposals with rapid implementation that included nutritional therapies, repurposed drugs, and ivermectin. So, I was like, I had to read it over like three times. Like, they're literally, uh, asking, at least in, in Florida, for proposals, $2 million proposals that would include ideally nutritional-based therapies, repurposed drugs, and ivermectin. And I was just like, this is, this is sort of, you know, maybe Florida's a little bit more innovative at the state level and asking, but they are very imple, and it was just a 12 weeks, and it had to be something that could be rapidly implemented in patients. So hopefully the NIH can embrace that spirit of things outside of mainstream on.

>> Are you going to apply for that grant? >> I'm working on that today. [laughter]

>> I use ivermectin all the time. And my blood levels of ivermectin are off the charts because we have this pour-on that you do with the cows and everything, and I just rub it in. I never even wear protection. But we do it, you know, you could do it orally, sub-q injection, or the pour-on stuff, and I use that.

>> Well, we, we were planning to do ivermectin studies, but it became such a hot political topic, I didn't want to get into it, uh, way back a couple of years ago. But, but, you know, we, we have a paper in bioRxiv now, but it's going to, it's under review for a bigger journal, um, on embendazole, the parasite medication, knowing that embendazole targets glycolysis and glutaminolysis pathways, uh, and when you put it under calorie-restricted ketosis, it works. It works really, really well. We haven't tested ivermectin yet, but we, we have that in the plan, uh, uh, to look, to look at, at that. It, because it turns out that the parasites, and so many people make a mistake. They say cancer is a parasite. Cancer is not a parasite. But parasites and cancer cells use common metabolic pathways for survival. And some of these parasite medications that wipe out these parasites do an effective job in wiping out the cancer, especially, especially when you're in nutritional ketosis. So again, repurposed drugs, but again, they're very cheap. Um, they're not like big blockbusters that are going to make the drug companies billions of dollars. Um, that doesn't mean that, doesn't mean we can't find new glutamine-targeting drugs or things like this. Um, but, but we're certainly realizing that repurposing drugs, again, as I said, all of the majority of what we need for managing cancer is already there. We just have to know how to use these things better. Um, Don, six-deoxyglucose, the best glutamine-targeting drug that we, we can find, and we're learning now how to reduce its toxicity, especially under nutritional ketosis. So, so, so we're, and that's another thing, when you're in nutritional ketosis, so many of these other things work so much better.

>> Uh, everything works better when you're in nutritional ketosis. Uh, and all cancer patients should be in this state. Uh, and, yeah, the hybrid systems are coming in. Um, epigenetic mitochondria are the most powerful epigenetic system in the cell. They control the nucleus. They are the controllers of the destiny of the cell. They, when the nucleus needs to do something, it's usually under the, under the, under the direction of the mitochondria, because without energy, nothing works. So, so, um, so yeah, I'm, I'm, I'm enthusiastic about it, and I think there's going to be a real lot of major breakthroughs coming down the pike here in a very short period of time, hopefully. That's our, that's our hope.

>> Thank you very much to you both. This has been a really fruitful discussion. Um, I think Dr. D. Augustino, if you have to jump off the call.

>> Yeah, I do have to jump off the call, but sort of, I want to mention that in the, in the time that I've been in this, you know, short interview, I've gotten about five messages from patients about, and one is from an oncologist, you know, asking for more information about this for themselves. So, uh, so this is, you know, an emerging topic of great interest, and I think just getting more awareness, um, out there and educating people on this will hopefully stimulate the conversation to make, you know, funding more available, um, and to develop resources and protocols that are, that, that could be available for patients. And I think that's the most important thing. I, >> think you both are doing a great job and bringing this information to the public. I'm very excited to get this video out here. Thank you, Morgan.

>> Thank you very much for your time.

>> You know, thank you very much for your time as well.

>> Thanks for hosting, Morgan. Appreciate it.

>> A pleasure. It was my pleasure.

>> Open for a part two anytime. It was good seeing you, Tom.

>> Yeah, great seeing you, Don.

>> Jump into teaching.

>> Yeah, you [clears throat] take it easy now.

>> Thank you.