The Science of a Keto Diet - with Dr. Dominic D'Agostino | The Empowering Neurologist EP. 49

Hi everyone, Dr. David Perlmutter here. We're going to talk today more about ketogenic diet, the role of ketosis. In other words, a diet that allows your body to use fat as a fuel source as opposed to glucose derived from carbohydrate. But we're going to look at this from a more of a research perspective in terms of the nuts and bolts as to what is going on when the body is exposed to these chemicals called ketones, which are the byproducts of utilizing fat in the body for energy. We're going to be talking with Dr. Dominic D'Agostino. He is at the University of South Florida. He's an associate professor in the Department of Molecular Pharmacology and Physiology. Hi. at USF, University of South Florida Morsani College of Medicine. He's also a research scientist at the Institute for Human and Machine Cognition, IHMC. His laboratory develops and tests nutritional strategies as well as various metabolic-based supplements for neurological disorders. In fact, you'll see that he's even exploring Lou Gehrig's disease through the notion of targeting mitochondrial function as it relates to that disorder. He's involved in studying cancer as well as enhanced physical performance and resilience of the human body in extreme environments, especially those environments in which there is elevated oxygen and oxygen pressure. His research is supported by the Office of Naval Research, Department of Defense, as well as various private organizations and foundations Really an interesting individual, adding a lot to our knowledge base. So let's just jump right into this interview. Well, hello, Dr. D'Agostino. How are you doing today?

I'm doing great. Thanks for having me.

Thanks for being here. Several weeks ago, we had the opportunity to interview Dr. Thomas Seyfried, and obviously some really groundbreaking work that both you and he are involved in. And this kind of is an extension of the original work on ketosis from the late 1920s as an effective treatment for epilepsy, particularly in children. More recently, the work of Dr. Mark Mattson and others related to caloric restriction and its effects. But why don't we start by just having you explain what it is that you do day to day and why that's interesting to you?

Okay. Sure. I was trained as a neuroscientist for my PhD at Rutgers University, and I— my— the path of my research went down the road of understanding extreme environments as it pertained to Navy applications. So in particular, undersea environments and preventing oxygen toxicity seizures. was really the focus of my funding. And in the process of doing that, we were developing technologies that would allow us to understand how the brain functions. So we had various imaging technologies to understand brain signaling. And it became very apparent that preserving brain energy metabolism was absolutely crucial for preventing seizures from oxygen toxicity. Right. I realized this before I even knew of the ketogenic diet or of its clinical application for pediatric epilepsy at the time.

You were involved in research that looked at the fact that too much oxygen, as somebody might be exposed to, for example, in hyperbarics with a higher percentage of oxygen, something that we were certainly cognizant of, can induce seizures, but what you're saying is if you could enhance the metabolism of brain cells, that that might prevent or lower the risk of that event from occurring. And then you came upon the idea of enhancing brain metabolism by pursuing a ketogenic diet.

Yes, that's right. I was primarily looking at drugs, and oxygen toxicity seizures are experienced by Navy SEALs that use a closed-circuit rebreather. And anti-epileptic drugs are not a very viable mitigation strategy. They're not viable for someone to take prior to a mission because of the impairment of warfighter performance and all the side effects associated with it. So in the efforts to understand oxygen toxicity and to mitigate it, we went down the path of like, what do epileptic patients, children with epilepsy, or now even adults do when drugs fail, and discovered the ketogenic diet and its its accepted application for drug-resistant seizures. And then I went down the path of doing ketogenic diet research and then developing strategies that could acutely induce ketosis to provide ketones to the brain for neuroprotection and for anti-epileptic effects, and later actually with cancer in some of the work that I did with Professor Seyfried.

So you've learned then that a ketogenic program is really very effective in enhancing the efficacy, how brains utilize fuel in terms of efficiency, in terms of reduction of free radicals, in terms of more bang for the buck, in that you're harvesting, making ATP from fat as opposed to glucose. And it seems to me that in your writings that you've really been able to throw a wide net now in terms of the brain in general, well beyond oxygen-induced epilepsy. So what are some of the kinds of things that may, you think, be areas where we could apply your findings to in terms of a more ketogenic diet?

Yeah, that's what's really exciting to me is that when I got into this field in 2008, Johns Hopkins, the group there, it was John Freeman at the time. who's passed away, but his colleague, Eric Kossoff, had written a book and the title of the book was The Ketogenic Diet for Pediatric Epilepsy. And that was really one of the only books out there at the time. And there was some work by— more of a mechanistic book by Jeong Rho, delving into the mechanisms of ketones and how ketones can Impact neuronal energy metabolism to reduce the production of oxygen free radicals, or reactive oxygen species. And it was— the theory of oxygen toxicity is that there's a breakdown of cellular energy metabolism and an overproduction of oxygen free radicals from the oxygen itself. So we know free radical production is proportional to the level of oxygen. Uh-huh. in the brain, and that was some work that I did as a postdoctoral fellow in hippocampal brain slice preparation where we exposed brain tissue to graded levels of oxygen and saw a proportional increase in oxygen free radicals. But what became apparent as we're studying metabolism is that if you preserve brain energy metabolism and supply energy in the form of ketones, that there's proportionally less— Yeah. So you're

getting the best of both worlds, it seems, that are being produced— energy metabolism, and at the same time—

And that's a consequence primarily—

Yeah, at the same time, you're diminishing the reactive oxygen species.

Yes, that's right, just by enhancing ATP production in the cells.

You know, one of the concerns of hyperbaric oxygen has always been enhancing the production of these reactive oxygen species. There's been some work that has indicated that these ROS actually enhance activity of pathways like the NRF2 pathway that actually ultimately enhances the body's production of protective antioxidants, detoxification pathways, and reducing inflammation as well. It seems that there might be some sweet spot then, a fine line whereby we do get this epigenetic benefit while at the same time, uh, we have to be cognizant of the potential downsides.

Yeah, that's right. So the therapeutic ranges of hyperbaric oxygen therapy, the limit is 3 atmospheres of oxygen. And when we study oxygen toxicity in the models in the lab, we actually go down pretty deep, uh, to 5 atmospheres of oxygen, which would be 132 feet of seawater. And if you or I were exposed to 5 atmospheres of oxygen, it would give us a seizure in about 10 minutes, whereas if we were in a state of deep ketosis from therapeutic fasting, the ketogenic diet, or even synthetic ketones, we could stay at 5 atmospheres of oxygen for like an hour or more. So it's a very dramatic— and there's no anti-epileptic drugs that can actually provide the same neuroprotection.

Okay, then let's extrapolate, if it's fair to do so, from the notion of protecting the brain from this artificially induced environment of high atmospheric pressure oxygen toxicity to more general ideas in terms of protecting the brain from free radicals, whether they're oxygen or nitrogen based, day to day, with the understanding that Really, it is the effect of these radicals long-term compromising mitochondrial function that activates apoptotic pathways. What can we say to the common man then in terms of the notion of engaging ketosis as being good for the brain?

Yeah, well, there's emerging data to indicate that a state of ketosis is beneficial for the brain, not just because ketones are an energy metabolite that have maybe superior bioenergetic effects as far as making ATP, but they have signaling properties that are independent of their role as an energy metabolite, and that can be actually having epigenetic effects and activating genetic programs that, for example, enhance endogenous antioxidant systems. One of the studies that we did at Yale University with our colleagues there and We published it in Nature Medicine about a year or so ago, was that it suppressed inflammation through suppressing the NLRP3 inflammasome. And that inflammasome is tightly linked to many age-related chronic diseases, autoimmune diseases, so— and it's suppressing that inflammasome independent of its effect on metabolism. And 10 years ago, we did not Even understand that these energy metabolites had effects independent from energy, but it makes sense that you would want to have epigenetic regulation or suppression of inflammation, that these metabolites are linked to

that. Correct me if I'm wrong, but you were very careful to delineate the effects on the inflammasome of beta-hydroxybutyrate versus acetoacetate. Am I correct in that?

Yes, so beta-hydroxybutyrate had a more robust effect, a significant effect at inhibiting inflammation. And it's really interesting that these 2 ketone metabolites do— beta-hydroxybutyrate actually needs to get broken down to acetoacetate to be used as energy. Acetoacetate, on the other hand, was vitally important for the seizure protection. Okay. And we think acetoacetate spontaneously decarboxylates to acetone, and that can impact a potassium channel that hyperpolarizes the resting membrane potential and can suppress glutamate-associated excitotoxicity that's associated with oxygen toxicity. So it can get kind of complicated. I don't want to get too much in the weeds, but beta-hydroxybutyrate and acetoacetate have similar effects on many systems, especially when it comes to exercise performance and maybe some other pathways with neuroprotection, but they have distinct regulatory effects independent of their roles as an energy metabolite. And that's really the area that our research is going in.

Let me segue to another area of your research and your publication. You mentioned just now glutamate, for example. And there is this glutamate hypothesis that relates to ALS, or Lou Gehrig's disease, that there is a deficiency of uptake of glutamate from the astrocytes, and therefore higher levels of glutamate that might be responsible ultimately for the neurodegenerative pathway in the motor system that's involved in ALS. And in fact, we'll talk about your study looking— evaluating the decrease in I'll glutamate uptake in the motor system. talk about the Yana Protocol in just a moment. It's very interesting then that when we look at research in the laboratory animal that has studied survivability and motor functionality in the ALS model of the rodent model, but enhanced being on a ketogenic diet, that you seem to be narrowing it down then to possibly involving this glutamate toxicity idea. Yeah. With the subsequent mitochondrial toxicity brought on by this NMDA stimulation by glutamate, enhanced by glutamate rather, with influx of calcium and ultimately proving toxic to the mitochondria?

Yeah, glutamate is involved in every neurological disorder or neuropathology or degenerative disease that I can think of. I can't think of any that are not, where you don't have glutamate-induced hyperexcitability and excess stimulation of AMPA receptors, and also with depolarization, you can also activate NMDA receptors, and overexcitation of NMDA receptors can then trigger a cascade that can lead to cell death and apoptosis and things like that. So energy metabolism is intimately linked to glutamate excitability simply by Preserving the membrane potential, which is an ATP-dependent process. Ketones, which can come from the diet or fasting or a supplement, is a very powerful strategy in our hands from reduced model systems, whether it be in vitro dissociated cell culture preparations, a brain slice preparation, an animal model, to a human patient. Right. Ketones have been shown across the board to provide energy that can help really preserve brain energy homeostasis, and that is linked to glutamate levels in the brain and glutamate homeostasis. So we are targeting that. That's part of the Deanna Protocol and many other things that we do.

This is great. I'm loving this because over the years we've looked upon this NMDA receptor and pharmaceutical attempts to modulate that using Namenda. Yeah. And now we're looking at a far more physiological approach to its regulation and its transmembrane issues that you mentioned in terms of influx by using a ketogenic diet. Let me go back, if I could, just to emphasize for our viewers, many are talking about beta-hydroxybutyrate, as you are, in terms of providing an adequate or a superior fuel and its breakdown products, superior fuel for cerebral metabolism. But you'd mentioned it, not— we'll get to signaling molecule in just a moment, but as an epigenetic player through— I don't know if you mentioned, but it would be one of the considerations as a histone deacetylase inhibitor.

Yes.

So, I think just that really opens up an interesting area of discussion. That one thing that you are doing by going on a more ketogenic diet is to enhance, through this epigenetic pathway, the expression of genes that have positive effects in terms of enhancing antioxidant coverage and reducing inflammation. So can you expound a little bit more on kind of the epigenetic role of the ketogenic approach through the actions of beta-hydroxybutyrate? Yeah.

Yeah, it was thought for many years that many of these effects of calorie restriction and therapeutic fasting were derived from the suppression of blood glucose and, I guess, more importantly, the suppression of the hormone insulin. And then that would kick on a variety of things and autophagy is another thing. that may or may not, are probably not influenced by ketones alone, but tend to be happening, well, we haven't shown that yet. But it is work by Eric Verdin and colleagues demonstrated that the ketone beta-hydroxybutyrate specifically functions as a class 1 and class 2 histone deacetylase inhibitor. And that HDAC inhibitors, as you know, and maybe your audience is aware, They are probably one of the most intensely studied class of drugs out there. They're used for a variety of applications as anti-cancer agents. They're being studied for a broad range of disease pathologies, and it's remarkable that we have an endogenous metabolite that is a powerful histone deacetylase inhibitor, and it works very specifically. Yeah. specifically in a way that's independent of its role as an energy metabolite. And there's ongoing research now to really figure out what pathway it's working through as a histone deacetylase inhibitor. And I think it's perhaps doing it through a number of pathways, but it's doing it independent of energy metabolism. And a consequence of that, at least in the models that have been studied so far, is there's a fairly robust increase in endogenous antioxidant capacity, which helps to protect the cells from a variety of challenges that would otherwise cause cell death and inflammation and excess oxidative stress, most importantly. So, it's remarkable that we have an endogenous metabolite that we can make via an eating regimen like that advocated by Mark Mattson from the NIH for years now, intermittent fasting, carbohydrate-restricted ketogenic diet, and perhaps even supplemental ketones in the form of ketogenic fats like medium-chain triglycerides or even ketone esters, which are being studied now.

So we've talked about beta-hydroxybutyrate as a fuel. We've talked about it as an epigenetic player, as a gene expression modifier. We also know that it acts on G-protein receptors as a transmembrane initiator influencing intracellular activity. So, you know, there's some positive outflow of that as well. Could we look at that for just a minute?

Yeah, well, it's not something that we directly study in the lab, so I can't really talk about our research involved in that, but I can talk more about its anti-inflammatory effects. That's what I'm a little bit more familiar with, especially its role in suppressing the NLRP3 inflammasome, but I think the jury's still out on its specific roles on receptors. So it may be mediating it not as a direct kind of ligand to the receptor but through redox control. So there's many proteins that are on, or amino acid residues on ion channels that are impacted by the redox state of the cell, the oxidative reductive state, and we know that ketones have a pretty dramatic impact on that. So just like oxygen, Studying oxygen was my background in my PhD and my postdoctoral work, and many of the oxygen-sensitive systems in our body are not really sensing oxygen, they're sensing reactive oxygen species. Uh-huh. And I think— and it's been demonstrated in our lab in numerous model systems that you have a pretty profound shift in the redox state of the cell. And intracellular reactive oxygen species and even extracellular, which would be hydrogen peroxide because it can permeate, you have pretty big shifts in these reactive oxygen species that impact G-coupled protein receptors. The NMDA receptor has a redox sensitivity to it, as do many of these others. So it's kind of a whole— Yeah. interesting field to study. It's very difficult to study it from a mechanistic standpoint, but I think that may be conferring some of the neuroprotective effects that we see with ketones. And I think it's an underappreciated area of research. And I say that because we're kind of studying it. And we know the impact of it because we do experiments where we simultaneously measure free radical production in the cells and neuronal activity with and without ketones. So we see these big redox shifts and we understand that we're not just impacting metabolism, we're impacting all the redox-sensitive pathways that are intimately linked to that neuronal excitability or suppression of excitability.

Well, I think the take-home message then would be That it's a much more comprehensive picture, much more pervasive influence that things like beta-hydroxybutyrate have on regulatory systems, well beyond serving just as it happens to be an efficient fuel. Yeah. As you would expect, though, as we move forward and recognize that things have roles to play across many spectra. So that said, let's get back to ALS for a moment if we can. And you had mentioned, in fact, you published a paper on the assessment of the Deanna Protocol. I knew Deanna and her father as well early on when— why don't we— you know the story, or if not, I can recount it.

Oh yeah, I know it pretty well, but I came in a little bit later into the story than you did. I think I met Dr. Tedone in maybe 2012 or '13, or '12 I believe, or maybe as early as 2011. And he described the supplements that he thought were having a therapeutic effect and described many supplements. And so I went to the literature and just kind of teased out, well, what can we extract out of what he's using that have scientific support? support behind it as a therapeutic agent. And we basically chose a variety of supplements that had research support behind it. And we incorporated those and tested that in the S51G93A mouse model, which is the familial form. So Deanna has sporadic ALS that's with unknown etiology, although Dr. Todone now thinks that Lyme disease may be part of that, and that's something that he's looking into. So we just He just chose to study the Deanna Protocol supplements, but the Deanna Protocol is kind of more comprehensive in what is being applied.

And again, for our viewers, this is a general— I believe he was a general surgeon whose daughter became affected with a sporadic form of Lou Gehrig's disease. And the discussion that we had years ago was that this is ultimately a mitochondrial event That ultimately triggers these pathways that are involved in pre-programmed cellular death, or apoptosis, which are initiated, in fact, by mitochondrial dysfunction. And we were exploring, even back then, the use of a ketogenic diet, extrapolating from early rodent studies demonstrating increased longevity, without really fully understanding all the pathways that you were just— Right. able to enumerate for us. But that said, so he, you know, he took it upon himself to do the literature work and come up with a protocol for his daughter. And now you have actually used, you know, similar approach in the rodent model, and your work does demonstrate increased preservation of functionality as well as longevity, I believe, in the rodent model using That's right. An approach designed to enhance mitochondrial function, which is really founded, I think, on first supplying that really efficient fuel, and now with the understanding of the various other pathways that are being utilized by the various ketone bodies to further preserve mitochondrial function, reduce inflammation, and enhance antioxidant coverage.

Yeah. Yeah, so that's right. We saw an improvement in neuronal function, or the neurological score, I should say. And there was an increase in motor function, and which has not been shown in a whole lot of ALS therapies that have been tested, but extension of life that was significant, statistically significant, in this ALS mouse model. That's a very aggressive mouse model. Working with these mice is kind of tricky because they have, many copies of the gene that result in the mutated SOD1. So, it's not a deficiency of the enzyme, it's an overproduction of a mutated form that causes it. And there's more copies that would probably— than in the mouse model than would probably be present in the human. So, the deterioration happens very rapidly. So, it allows— Kind of for a useful model to screen out and vet out various therapies that may have an effect?

There is a bunch of research happening now looking at the microbiome in ALS patients. One study's underway at MGH. And interestingly, there is the thought that there are certainly changes, if not a unique fingerprint in the microbiome, that is characteristic of ALS. And it's interesting to try to kind of fathom how this might relate to the discussion that you and I are having right now. And I will tell you that, you know, what we understand about loss of bacterial diversity and changes in the microbiome is often a hallmark of that are changes in the ratios of the short-chain fatty acids. So, You know, we know that butyrate acts in many ways similar to beta-hydroxybutyrate in terms of cell signaling and also in terms of serving as a histone deacetylase inhibitor. With changes in the microbiome and changes presumably in butyrate, that might be a unifying point between the work that you're doing and the research that goes on with reference to exploring the microbiome. And that said, It might open the door to both reestablishing a healthy gut bacteria, which is not part of the DNA protocol, as well as specifically through supplements and dietary changes targeting mitochondrial function to upregulate mitochondrial health and resistance to initiating apoptosis. So, I think we're going to see a convergence of these 2 seemingly disparate areas. Therapies for mitochondrial function and changes in gut bacteria actually sharing a similar butyrate-based mechanism, and that I think may open the door to some real potential for recovery, or at least stabilization for these individuals.

Yeah, that's a really good point. The fiber that's part of the diet produces these short-chain fatty acids and the colonocytes really thrive off of these short-chain fatty acids like butyrate, and a disruption of that can impact a number of processes including the tight junctions that are associated with the barrier that's needed. And there's a very similar theme in people who get ALS is that many of them are exposed to an environment or a toxin or perhaps a pathogen that— and all these things can disrupt the gut microbiome or have links to disrupting the vascular permeability and impacting these tight junctions. So I see a kind of a unifying theme there among, at least with people contacting me, and even within the military. You tend to— these guys get moved around all over the place and we know that our gut microbiome changes in response to You know, our geographical location. And if we're moved to multiple locations and stressed at the same time, I think that can predispose us to a number of neurological disorders, including MS and ALS. So that's been observed. But the link is very difficult to make, a conclusive link, because I think there could be— with familial ALS, we know the cause, but for sporadic ALS— The etiology is largely unknown, and I think it's really important to look at the microbiome as being part of that, especially the barrier function.

That the SOD model really does help us because it's clear where that lets us into the mitochondrial dysfunction. We get that. But having said that, as you mentioned with the military individuals who are exposed to jet fuel or whatever, or Yeah. Soccer players, professional soccer players in Europe, and they're exposed to pesticides on the soccer field, that there are other ways of inducing mitochondrial dysfunction, even via disruption of the microbiome, that can also get you on that carousel to lead to this feedforward process, whether it's inherited or otherwise. So I think it still allows us to, as you say, use that SOD model in a very effective way, because it's much more rapid and defined. This is our problem, and how do we go about fixing it? Now, there was a study, I believe back in 2005, in the journal Neurology, that looked at a ketogenic, a hyperketogenic diet in treatment of Parkinson's patients, humans.

Yeah.

And demonstrated really a profound improvement on the Unified Parkinson's Disease Rating Scale in the various parameters that were looked at in terms of medication response, mobility, et cetera, really profound changes that rivaled medication even to this day. Why is there such a pushback in clinically relevant journals to explore— I wouldn't even say embrace, but to explore The utility of a ketogenic diet, for example, in the neurodegenerative conditions. Why such reluctance?

Well, I mean, there's a lot of reasons for that, especially in regards to cancer too, which is an area that we study. But the one study that you mentioned with Parkinson's disease patients, I know one of the authors very well. Dr. Theodore Van Itallie, and I believe he's in his late 90s, mid to late 90s now. And I talked to him and various colleagues of his that are trying to advance this idea of nutritional ketosis as being therapeutic in many ways. But with Parkinson's disease and other diseases like Alzheimer's disease, I think there's There's a major emphasis from at least the funding agencies like National Institutes of Health and even the Alzheimer's Association, although they did fund a ketogenic diet study with a mouse model. There's a big emphasis on a magic bullet and targeting tau and targeting amyloid plaques and creating antibodies that can prevent the accumulation of these— Amyloid plaques. Plaques and tangles that we see. And that's where the research is really going, whereas research with nutrition is just a little less tangible and there's just not a lot of support in mainstream medicine for nutritional interventions for treatment or, you know, probably most importantly, prevention. Right. The support is not there from the funding agencies. And I think that is part of it, right? Because the National Institutes of Health really fund the research that get high visibility in the academic system. So, and that's where top-tier researchers are expected to get NIH funding to develop and maintain the research program. And if there's not funding available from the NIH to do basic science and clinical science with nutrition, then that becomes a problem because it becomes difficult to validate. And even running a clinical trial with the ketogenic diet, it's quite difficult for these things because you have to get a clinician who understands the ketogenic diet, which is sometimes difficult. You need to get— Dietitians, many of them don't understand the diet in a way that they could get patients to comply, so they need to get a nutrition dietetic team to work with the patients, and then the patients have to comply, and the institute has to be welcoming to the idea of using this as a therapy for these diseases. And on top of that, The IRB, the Institutional Review Board, the ethics committee, has to approve it. So you have many, not just the funding, but you have many different hurdles to make this happen. And I think that limits the amount of quality, high-impact peer-reviewed publications that come out to support the ketogenic diet as a valid metabolic therapy.

Well, we in clinical medicine, I think, are all You know, gun-shy of the word ketosis.

That too.

You know, up in the middle of the night dealing with a diabetic in ketoacidosis, you know, that would be about the worst thing you could imagine. And yet it's so unfortunate that that experience is the tag-along with the whole notion of ketosis being a very positive experience. So I just want to applaud you for the great work that you're doing. This is the foundational work that those of us who are involved in looking at interventional types of medicine really, really need to be able to hold up and say, here's why. Here's why we recommend for an ALS patient a ketogenic diet. I mean, there's no downside, and here's the potential upside. Here's at least what the animal research shows. So, I want to thank you for my— For me, as well as for all of our viewers, for all of your great work. And I want to encourage you that there are a lot of us out there who are following you and who desperately depend on every bit of work that you do. All the work that you do is really, again, very supportive of open-minded clinicians who are willing to go ahead and make these changes in recommendations to patients. So thanks.

Thank you for giving me this platform to speak. And I'd just like to say, in the short time that I've been studying this, I've seen this field grow tremendously and the amount of clinicians that are coming into it and basic scientists supporting the research is really growing tremendously. And we hosted the 2nd Annual Metabolic Therapeutics Conference and had the Johns Hopkins ketogenic diet team down here to talk and many other— we had hundreds of people at it. So there is a lot of interest in this field and I think it's serving people in a tremendous way. Yeah. And I think whenever you're doing that, people will recognize kind of the value that this therapy brings to them. And I think it's just going to gain more traction and get bigger.

And I think, you know, just from a recommendation perspective for our viewers who may be interested in looking into this further, even for themselves, that is that it's not just a question of adding in the appropriate fats, but you've got to restrict the carbs and sugar. Yes. In order to let your body selectively utilize these fats and your endogenous fats available through liver being processed as well to manufacture these ketones that we're talking about and therefore have them available. But it's not going to work when there are— when you continue to give your body the carbohydrates, it's going to preferentially use sugar and carbs. So to make it happen, it's not just the addition of the fat, but it's the restriction of the glucose and the carbs. And what would you say to people who want to explore this further in terms of what they should be looking at, what conference they should go to, or what book should they be reading?

Yeah, well, your book, of course, is a great primer. Yeah, and great introduction into brain health and the importance of not just macronutrient profile, but food selection. The go-to resource that I usually direct people to, especially clinically, is the Charlie Foundation website. And I think it's a fantastic website. The Ketogenic Diet Resource has also been— I mean, there's a book on there written by a medical doctor that's a type 1 diabetic that describes the use of the ketogenic diet for type 1 diabetes, which is unheard of, right?

Yeah.

One of my PhD students is a type 1 diabetic and does remarkably well on a ketogenic diet. He requires far less insulin and can keep his glucose in tight control using that. And that would be unheard of just 10 years ago. So the ketogenic diet resource I think is great, the Charlie Foundation, and I have a website, ketonutrition.org. Okay. And on that website, if you click on resources, it will bring you to a list of dietitians and registered dietitians and consultants that can help patients. There's a, you know, clinical trials are listed there, a number of books, ebooks, and other books that are listed, podcasts. So I try to provide, you know, my website as a link to— there's nothing for sale on there, it's just information. But a lot of information that I think can be helpful to your listeners.

So again, ketonutrition.org. It should be—

.org.

Bottom of your screen, you should see that.

Yeah.

Dominic, thanks for joining us today. Really, really interesting conversation. And again, thanks for all you do. It's great stuff.

Thanks for having me. I appreciate it.

Bye for now.

Bye-bye.

See that I was very taken by today's interview. What an amazing researcher! What a dedicated individual! He is exploring again the the real nuts and bolts as to why ketosis matters, and the very powerful potential that a ketogenic program has, especially as it relates to the brain, brain function, brain preservation, and even from an interventional. perspective in the treatment of existing disease. Well, thanks for joining me on The Empowered Neurologist. I'm Dr. David Perlmutter.