The Melanie Avalon Biohacking Podcast
The Melanie Avalon Biohacking Podcast

Episode 1 · 5 months ago

#150 - Dom D’Agostino: Ketogenic Diets, Exogenous Ketones, Measuring Ketosis, Long-Term Keto, Fasting & Caloric Restriction, Metabolic Flexibility, The Dawn Effect, And More!

ABOUT THIS EPISODE

GET TRANSCRIPT AND FULL SHOWNOTES: melanieavalon.com/domdagostino

2:25 - IF Biohackers: Intermittent Fasting + Real Foods + Life: Join Melanie's Facebook Group At Facebook.com/groups/paleoOMAD For A Weekly Episode GIVEAWAY, And To Discuss And Learn About All Things Biohacking! All Conversations Welcome!

2:40 - Follow Melanie On Instagram To See The Latest Moments, Products, And #AllTheThings! @MelanieAvalon

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5:20 - FOOD SENSE GUIDE: Get Melanie's App At Melanieavalon.com/foodsenseguide To Tackle Your Food Sensitivities! Food Sense Includes A Searchable Catalogue Of 300+ Foods, Revealing Their Gluten, FODMAP, Lectin, Histamine, Amine, Glutamate, Oxalate, Salicylate, Sulfite, And Thiol Status. Food Sense Also Includes Compound Overviews, Reactions To Look For, Lists Of Foods High And Low In Them, The Ability To Create Your Own Personal Lists, And More!

6:00 - BEAUTYCOUNTER: Non-Toxic Beauty Products Tested For Heavy Metals, Which Support Skin Health And Look Amazing! Shop At beautycounter.com/melanieavalon For Something Magical! For Exclusive Offers And Discounts, And More On The Science Of Skincare, Get On Melanie's Private Beautycounter Email List At melanieavalon.com/cleanbeauty! Find Your Perfect Beautycounter Products With Melanie's Quiz: melanieavalon.com/beautycounterquiz

10:30 - NASA's NEMO

12:50 - The Aquarius Habitat And Hyperbaric Effect

17:55 - Performance Ketogenic Diet

19:15 - CNS Oxygen Toxicity

21:25 - Dom's Research Into The Ketogenic Diet 

23:45 - Anti Seizure Drugs Vs Keto

26:30 - What Makes Keto Beneficial?

28:50 - Seizure Control With Other Low Carb Diets

29:45 - SUNLIGHTEN: Get Up To $200 Off AND $99 Shipping (Regularly $598) With The Code MelanieAvalon At MelanieAvalon.Com/Sunlighten. Forward Your Proof Of Purchase To Podcast@MelanieAvalon.com, To Receive A Signed Copy Of What When Wine!

31:00 - Root Cause In Seizure

34:00 - The Spectrum Of Ketosis

35:30 - Becoming Fat Adapted

37:20 - Higher Resting Blood Glucose On Keto

38:00 - The Dawn Effect

41:50 - Cryotherapy, Ketones, And Blood Glucose

45:00 - Why Do We Enter Ketosis?

48:30 - Acetyl CoA

50:20 - Starvation And Metabolic Disorders That Prevent Ketosis

55:10 - The Inuit

56:30 - Long Term Ketosis

58:40 - Is Chronic Ketosis Healthy?

1:00:25 - Fat Adaptation Through Restricted Carbs Vs Restricted Dietary Fat

1:04:40 - Ketones And Mitochondrial Uncoupling

1:12:30 - Lactate

1:15:20 - Ketones To Fuel The Brain

1:18:00 - Strict Keto With Carb Cycling Vs Moderate Carb Keto

1:20:45 - NUTRISENSE: Get Your Own Personal Continuous Glucose Monitor (CGM) To See How Your Blood Sugar Responds 24/7 To Your Food, Fasting, And Exercise! The Nutrisense CGM Program Helps You Interpret The Data And Take Charge Of Your Metabolic Health! Learn More About Nutrisense In Melanie’s Interview With Founder Kara Collier At melanieaalon.com/nutrisense. Get $40 Off A CGM At nutrisense.io/melanie With The Code MelanieAvalon

1:24:15 - Ketone Bodies And Measuring Ketosis

1:30:30 - Acetone On The Breath

1:34:10 - Acetone For Anti Seizure Effects

1:35:50 - Personalizing The Ketogenic Diet For Our Genetics

1:38:15 - Exogenous Ketones Vs Endogenous Ketones

1:40:40 - Salts Vs Esters

1:44:10 - Can We Become 'Ketone Resistant'?

1:45:55 - Chasing Ketones

1:47:45 - 'Metabolic Memory'

1:51:00 - Is Keto Pro-Cancer Or Anti-Cancer?

1:55:00 - Pairing Keto With Cancer Treatments

I embarked on this idea of developing a ketogenic diet in a drug which led me to develop keytone esters and Keyton salts. The ketogenic diet is the only therapy that we know of that you can follow it for a period of time. It may be repairing and rewiring the brain and balancing brain neurow chemistry and the tablist. We don't know if reducing fluctuations in Glucose and non diabetic people will have long lasting benefit, but you get a hunch that it will. Welcome to the Melanie Avalon biohacking podcasts, where we meet the world's top experts to explore the secrets of health, mindset on jevity and so much more. Are you ready to take charge of your existence and biohack your life? This show is for you. Please keep in mind we're not dispensing medical advice and are not responsible for any outcomes, and we experience from implementing the tactics. Mind nearing. Are you ready? Let's do welcome back to the Melanie Avalon biohacking podcast. Oh my goodness, friends, I am so honored, so excited about today's episode. The concept of keytones, the Ketogenic Diet keytosis. Obviously that is a topic that I am thinking about all the time, especially with the intermitted fasting podcast and with all of the work that I've done on this show. And who is the go to authoritative figure you're on Keytones, but Dom di Augustino. It was honestly thrilling to bring him on the show and on top of that, he is just one of the nicest, kindest human beings. I don't know if we talked about this in the episode, but we actually had to trouble shoot for about an hour prior to recording because the connection wasn't working with his computer. So not only did he put up with that for an hour, but then he still continued to talk with me for almost two hours on all of these topics. I so enjoyed it. I got to finally ask all of those nitty gritty, granular questions I have about keytones. I think you guys are really going to learn so, so much and I can't wait to hear what you guys think. These show notes for today's episode will be at Melanie avaloncom Dom di Agostino, that's doom Dagostino. Those show notes will have a full transcript, so definitely check that out. There will be two episode giveaways for this episode. One will be in my facebook group. I have biohackers intermitted. Fasting plus real foods plus life. Comment something you learned or something that resonated with you on the pinned post to enter to win something that I love, and then find the announcement post on instagram on Fridays also comment there to again enter to win something that I love. Supplement update for you friends. Magnesium is coming. Are you on the email list? That is avalon x dot US email list. 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I am here today, honestly, with a legend, especially a legend probably that a lot of my audience is very familiar with, especially with me hosting the intermitton fasting podcast as well and talking all the time about the key toogenic diet, key tones, metabolic flexibility, all of that, and I was actually thinking about this before we started recording. I think when people think key tones, probably the go to source of information I think would be dom D Augustino. So it is no surprise that ever since I started this show a few years ago, he was at the top of my list of somebody to interview. So this is really a surreal moment right now, and it's actually kind of funny. I don't know if remember this, Dom, but I've been like trying to find my way to you. So I've been like asking all different people for an intro and I think to people the same day emailed you almost the exact same email connecting you or like offering to connect you to me, which was funny. Yeah, I Kirk Parsley and I forget who else? Brad currents? Oh, Brad Current. Yeah, yeah, I did his podcast recent. Yep, it's funny. It's guys that I know. Ye, yeah, it was just funny because I've been asking Kirk for a while and then I asked Brad and Kirk just happened to do it like the same day that Brad did. So you got hit with it with all the emails. But in any case, for listeners who are not familiar dom diagues, you know he's an associate professor with tenure at the University of South Florida and he teaches students of the Marsani College of Medicine and the Department of Molecular Pharmacology and physiology, and he focuses on an array of really...

...incredible topics like neuropharmacology, medical biochemistry, physiology, neuroscience and neuropharmacology. That should be a test for like young kids learning how to read and pronounce things. He is also a research scientist at the Institute for Human and machine cognition and he has a lab where he just does a myriad of incredible things that I'm sure we will talk about, and this is super cool. You are a research investigator and crew member on NASA's extreme environment mission operation. Where was that? Yeah, so the Nemo. NASA loves these ACRONYMS, right. So, and NASA extreme environment mission operation is a space analog research project that they use for training astronauts and it's in the aquarious habitat, which is off the coast. It's in the bottom of the Atlantic Ocean and it's off I le Marada. You have to boat ride about an hour out and then then you go underwater and then the habitat is actually it's hyperbaric. So it's at the same barometric pressure as the water you're down under. So you stay in a hyperbaric environment and you live in what's called saturation and it's, you know, it's extreme environment. Takes takes like seventeen hours for us to come back up from that level of pressure. So yeah, it's off the coast. It's the aquarious habitat, if you google that, and NASA uses that habitat for for training and they also use the neutral buoyancy lab at NASA in Houston to train astronauts underwater because it simulates neutral buoyancy. How long are you at that pressure? My mission was the Nemo twenty two mission and we were underwater for ten days and we have to do a variety of different, you know, task that NASA has in regards to your testing, different types of equipment, different procedures, you know, were I did a lot of medical testing, microbiome changes and things like that, skin microbiome, blood measurements, things like that. So and then my wife Actually was on Nemo Twenty three, which was an all female crew. Her commander was Samantha Christopher Eddie and Jessica Watson, who will actually be going up to space station and doing a launch in April along with my commander, she'll lingren, who was medical doctor and astronaut. He was my commander for for that. So it's weird. It's like the whole nemo crew is like reuniting and they're going to space. We're staying all wrong because my wife and I are just scientists and we assist with the project and organizing the research on the project and we became the crew members to you become aqua knots when you stay underwater for more than twenty four hours. So we officially became Aquadat. That is so cool. Okay, I have a question. Actually it's a parallel question for the keytogenic diet related to that. So ten days at that hyperbaric pressure, the findings that you find, because normally people are doing hyperbaric oxygen therapy or pressure chambers, I'm not using our terminology. Only were they doing that? They're during sessions, more cute sessions. So the findings that you get doing an elongated session, do they apply to the benefits that you can get from acute sessions, or do things happen at a longer session that you can only get if you're doing a longer session. With hyperbaric oxygen therapy, you get inside a chamber and if it's a monoplace chamber, the Chamber is flushed with the air which is twenty percent oxygen, is flushed with a hundred percent oxygen, and then that's pressurized typically to like, you know, above one point five atmospheres, to two and then up the three atmospheres maximum, and then you usually, you know, sustain that for about an hour or so, maybe maybe ninety minutes or depending on the pressure, and and then you do that. If it's for wound healing, for example, which is like an FDA approved application, probably one of the most common applications, you do that for like five days a week. And then if you're recreational diving you have things like decompression sickness, then you would just do like, you know, one exposure. But the aquarious habitat your breathing hyperbaric air. You're at about just about three atmospheres and what you're breathing is the air. There's like air that's that's pumped down into the habitat and that are is at. It is that, you know, we're at like sixty, depending on sixty to ninety feet of sea water, depending on what we're we're if we're doing the mission outside or inside the habitat. But hyperbaric air is, you know, not as high concentration as hyperbaric oction therapy, but you still have that pressure. So your body is saturated with nitrogen and you live. You're living in something called saturation, which means it takes a long time to decompress to get to the top. It's easier. My commander at the time actually before we decompress, he tweeted it took...

...longer for him. It only took like five hours to get from the International Space Station back down the ground, but it took seventeen hours to get from this extreme environment to the surface. Wow, because you have to do is what's called the stage decompression, like overnight in this habitat to get back up to the top. Or if you were to just shoot up to the top after the end of the mission, well, what happened? Your blood would boil and you would like have a freaky painful death, but that's from something called decompression sickness, so that the nitrogen would want to come out of solution and then that would get into your blood vessels. It would cause embolisms in your brain and your heart and your pulmonary system and you would die. So you have to do a very, very calculated stage decompression where the first hour of the decompression you pre breathe oxygen to help with the de nitrogenation. And astronaux actually do and oxygen pre breathe before they do a space walk. A space walk is when they come out of the International Space Station or whatever ship they're on. And then you know they'll work in space wearing a suit and but the suit is only pressurized to a quarter of an atmosphere. So what they'll do typically, and the Astro night after naut Mike Gernhart, who I know actually worked on this protocol, they get on a bike and they breathe oxygen and that helps them get more nitrogen out of their system and then they suit up into the space suit and then they go outside of the space station into space and do what's called the spacewalk. And but but that oxygen pre breathe is serves the same function. It helps to denitron in and the De nitrogenate the body so you don't get decompression sickness. Or the bends. Did you experience any side effects from any of it? No, I did, and part of the reason I stayed in a deep state of keytosis where my key tones were like elevated above my glucose almost for the entire mission and I took like Saliva, took R and samples to look at my nerve transmitters, I took tons of blood work to see how that environment environment changed me. Also wore the or ring, which we have sponsored it. Yeah, and so all the crew members, the ash from notts they had there were in the or ring and they also wore the Polar v eight hundred to get like deep heart rate variability, which is a little more complex than the ore ring, but it was good to compare that and it basically validated aura as like a great device for heart rate variability. And Yeah, we did tons of other measurements who looked at psychological measurements and microbiome and skin microbiome and all these different things. But yeah, the extreme environment. Well, a lot of research that I do is actually creating a state of Keytosis, whether dietary or supplemental, to preserve performance, resilience and environments where to make to make it more safe to operate in the environment and also increase your performance, whether that be cognitive and physical performance, which I have so many questions about. So is just fantastic. Out of curiosity on that mission, were you just following a dietary approach to achieve that ketogenic state, or were you supplementing with exhaustionist keytones, or what were you doing? I did both. So they have like this astronaut food tape things, which is like camping food that you can make. So the crew, the rest of the crew, was the idea was to like get see what happens to our bodies in extreme environment, eating what we normally eat. So the crew basically gets to pick from an array of foods, you know, aligned with what they typically eat what. But I was following a Ketogenic Diet. So when I was in this actually it was probably a little bit more ketogenic than normal and I was eating a lot of Sartine. or No, I couldn't bring Sartines, that's right. I wasn't allowed to bring startins because the smell actually, so I brought chicken. I know, it is like funny. I had a little things and they contacted me and they're like now sorting why. It was like an email back and forth. Okay, can you explain why? I can't. Brings are so apparently, you know, the smell could be kind of in that particular undersea habitat this smells are amplified. So yeah, I had a lot of chicken and olive oil and coconut oil and I brought ketones supplements down with me and I would consume the keytones supplements, for example, like before the oxygen pre breathe, because we actually study sing US often toxicity which when you're in Keytosis, it protects against that and we've published quite a bit in that area. And I would take the keytones before, for I did what was called an Eva, and eva is extra vehicular activity where you go outside of the Habitat. In the habitat you're dry but you're pressurized, and then with an eva you sued up and then you work in the water outside that habitat and four hours on end. So you and and you can sometimes you go down deeper to so you're at a higher pressure and you're also under a very you're very task loaded cognitively and then you're also there's pretty high physical demands too,...

...because you have to pull a cart and you have to like drill into the ground and get samples of coral and and build these coral I remember a big project was the coral refoundation, where you would get samples of coral and then bring it back and do like genetic analysis, but then you also you you basically make these coral trees to propagate certain types of coral that are endangered. I think citter Astrea was one of them. There's a few different types of coral that we were working with. That is so cool. We have the only one doing a Keto Diet. Yeah, the other everybody else was pretty interested and there are astronauts that I communicate with that, you know, follow a low carb ketogenic approach even on the station. But for me I was the only one doing that and the idea was to get baseline data. It's like what does because we had a whole bunch of experiments. You know, what does? This extreme environment due to our physiology, and then in other crews that were planning or the experiments, we can we can do an intervention like change a dietary parameter, you know, lower key tones and or lower carbohydrates and elevate key tone levels and things like that. But I got. I got a lot of data and some of it we've published and we've got a couple of their manuscripts working on. One other question, just to get my audience more familiar with your work and for me personally, I'm super curious what, if me, do you interested in this whole world of the key to Shnick Diet and key tones and what you're doing today? Was it like an epiphany one day or I did my Ph d in neur science and physiology and then my post doctoral fellowship was funded by the Office of Navy Research and they were essentially funding me to develop technologies to understand oxygen toxicity seizures, which is a limitation for navy seal divers that use a close circuit rebreather under like stealth operations. Right. So the advantage of these rebreathers is that there's no bubbles when you're swimming, but the disadvantage is that that's it's high oxygen because it's close circuit and it was pure oxygen. So we knew that if you go down more than fifty feet for even like ten minutes, your have you could potentially have a seizure. So we wanted to develop and understand how to predict these seizures and how to prevent them. And in the process of doing that I was very interested in different antioxidants and combining like even like Melotonin. I did some studies on Melotonin, which is actually a really, really good antioxidant has some interesting effects in and other more you know, antioxidants we use and they tend to work good in like in the lab, but in practice they don't seem to have good antiseizure effects. And then there's antiseesure drugs, but then they can dull your senses and make you sedated. So I didn't you don't want to load up a warfighter with antiseesuer drugs. So discovered that the Ketogenic Diet was actually used when drugs fail. So I became interested in implementing a high fact Ketogenic Diet, but the military did not like the idea of giving a navy seal a diet that was like eighty ninety percent fat. So then I embarked on this idea of developing a ketogenic diet in a drug which led me to develop keytone esters and keytone salts, and now I mean, we have like dozen two different molecules that were kind of playing around with to formulate the optimal therapeutic keytosis approach. And Different Ketogenic strategies can be employed for different scenarios, whether it be, you know, anti cancer effects or anti sesure effects or ner protective effects or blood glucose lowering effects. So there's there's different approaches for that. So, speaking to the the seizures and the drugs did normally to treat it and all that, I was reading your book the origin and future of the Ketogenic Diet that we're talking about before recording with Chavis Christopherson, and it was really upsetting to read, and not the whole book but the concepts that you discussed about how, you know, how these anti Caesar Drugs Typically worked and their success rate compared to the Ketogenic Diet success rate. But basically, the doctors and the pharmaceutical companies kind of you know, they're not going to really suggest the Ketogenic Diet because there's not funding behind it, there's not a pharmaceutical mode of there and then, on top of that they say that it's, you know, hard to follow. So they're kind of making the choice for especially like parents with kids with epilepsy, they're making the choice for them that the Keyo diets not really an option because compliance is too difficult. When the success rate is, I mean looks like, way, way, better than those drugs. Yeah, and and actually works. And like seventy percent of the patients where all were multiple drugs have failed in combination. So it's working through a mechanism that's independent of any particular drug. It's interesting because there's it's plaeotrophic, we say it's the key Jek Diet...

...is working synergistically. It's like many different mechanisms working synergistically together to enhance your brain function, balance your nerve transmitters and really protect you from seizures. And the ideology of epilepsy and many seizure disorders is largely unknown and the Ketogenic Diet works remarkably well for controlling seizures from a broad array of etiologies you know, or causes like a could be temporal little epilepsy, it could be absent seizures could be upilepped or seizures from Metabolic Disorders like glucose transporter deficiency or PDH deficiency. And there's genetic disorders where there's a persistent genetic problem, but the Ketogenic Diet works even in the presence of a persistent genetic pathology, which is very interesting. So you're not like correcting the gene, although we are looking at epigenetic changes. By following the Diet it changes your metabolic physiology, which changes your brain neuropharmacology and changes nerve transmitter systems. That can then you know it has an anti sesure effect and we don't know all the reasons why has such a profound antiseizure effect, but that's a lot of what we're doing in the lab now. It's investigating that. Yeah, that actually speaks to a question I had, which was a more general question, but it's what you were just talking about, because the Ketogenic Diet is linked to so many different health benefits with an array of issues, so not just seizures in general. Is it mostly the benefits from the keytones, from the keytones signaling, from the low carb aspect of what you're cutting out, the weight loss on a Ketogenic Diet? Like is there one thing that's more than the other, or is it just a myriad of things, and is there a for each different disease? Is like is it a similar effect for all the different conditions, or are some things it's at the specific aspect of the keep genet diet or keytones that are creating that help benefit? Such a good question. You know, this has been the topic of, you know, workshops and seminars at the American epilepsy society, which is largely a huge event with thousand, tens of thousands of people's mostly sponsored by drug companies. Right. But but they have within the American epilepsies society conference they have the special interest group on dietary therapies, which is the Ketogenic Diet. They don't even like to use a word, Kejek Diet. They call you know, special interest group on diether therapies. But within that all the experts come and we discuss this and in some cases it does appear that the seizure control correlates with the level of keetosis. But you can also say that that seizure control, that that the level of Keytosis also correlates with decreased glucose availability. The level of keetosis will be inversely correlated with insulin. So the lower we suppress the hormone insulin, the more our body is in fat burning mode and as the liver burns tons of fat, then we make more keytones from that fat. But there's certain disorders like glucose transporter type one Deficiency Syndrome, where the glucose literally can't get across the blood brain barrier. So when a child has this disorder, they could be relatively catatonic and not be able to get up and move at all. But when they enter a state of Ketosis this it's like it fires the brain back up again and they there, they become aware, they become alert and they can regain function again. So the keytones function as an alternative energy substrate, because the glucose cannot literally cross the blood brain barrier because the glut one receptor is deficient in that. So that would be a case where keytones definitely matter. And then there's other disorders that are being studied, like absent seizures and even like autism, things like that. We're something called a low glycemic index diet, which is like, you know, the high fat, moderate protein and low carb but not low enough in carbohydrates to really produce high levels of key tones. They're just like a just a moderate level of keytosis and then this has anti sesure effects to not as much as a classical ketogenic diet, but what's interesting and establish is that it's been shown that people can have seizure control with a lower carb diet that that's not necessarily keytogenic. So that's kind of interesting to you know, in that it doesn't necessarily need to be, you know, highly keytogenic to have anti sizure effects for some disorders, whereas other disorders you really need to get the keytone levels up high to control the seizures. Hi, friends, one of the most valuable things that I do every single night of my life is my infrared sauna session. The brand that I use is sun lighten. I did a lot of research on Infrad Saunas before deciding on them. Their SAUNAS are so high quality, their low EMF...

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Will also put that in the show notes. All right. Now back to the show. Would whether or not somebody with epilepsy who goes on a Ketogenic Diet and then goes off and you know, is okay, like they don't have to go back on it, versus those who, the teachers, come back, would that be indicating, I guess, if it's a different type of seizure or a different root cause, like are the multiple root causes for seizures. There are. Yeah, you know, Charlie Abrahams is probably a really good example. His Father Jim Abrahams to Hollywood producer who made the movie airplane and Naked Gun. He actually did that story and fired me to study the Ketogenic Diet and actually look at it when I fall. I saw the movie first do no harm with Meryl Street. So Meryl Streep did a movie about the Ketogenic Diet, which is kind of interesting and I saw it in two thousand and eight and as a science as. I was unaware of that the Diet was used for seizures. I just thought it was like in the fitness and bodybuilding circles, you know, people talked about the Keyto Diet, but I didn't. I didn't even know. I went through a nutrition program and I at ruckers university and we did not even really talk about the Keytogenek Diet as a medical therapy. But Charlie, Jim Abraham's found the ketogenic diet by going to the library and Got Charlie administered at Johns Hopkins where he got off all his medication was which had horrible side effects and Charlie was put on a very calculated ketogenic diet four to one ratio, which is like eighty eight to ninety percent fat, and then his seizures were controlled. He followed the Diet for a couple years and then weaned off of the Diet and never got seizures again. So the keytogenic diet is the only therapy that we know of that you can follow it for a period of time and you're able to wean the patient off of the Diet over particular time in some patients and then the seizures never come back. So whereas if you stop drug therapy, then you have a rebound effect and you have more seizures. So the Ketogenic Diet with that was telling me is that when you follow the Diet, it may be repairing and rewiring the brain and balancing brain neurochemistry and metabolism their way. That's actually fixing the brain and crying epilepsy. And then you could come and it seemed pretty far fetched, but that's what the literature was suggesting and that's you know, the researchers at Johns Hopkins and Mayo Clinic and Duke and other places show. These are called super responders. Not Everybody's like that, but about I think about anywhere between ten to twenty percent. Around like fifteen percent may have are what considered a super responders, which means they have rapid seizure control and they adhere to the Diet and then it they it never comes back. They're able to manage it with the Diet and then gradually been off the Diet and then the seizures never come back. So another question, because you're talking about, you know, people and moderate levels of keytosis and potentially seeing benefits. So there's definitely this idea. We definitely with me being the host of the Internet fasting podcast, a lot of the questions we get there's this idea that you're in Ketosis or you're not, like it's an on and off switch. Is it an on and off switch or is it more like a dimmer? Yeah, it is like a dimmer Rheostat or whatever you thinking like far as electronics. Yeah, it's a spectrum right. So, which is largely a result of the carbohydrate restriction. So as we dial and for our current clinical trial, we were using continuous glucose monitoring with the levels health app what we do with patients who are non diabetic. We put CGMS on them and we measure a whole bunch of parameters, including psychological, you know, depression. We look at anxiety and things like that and how that changes, in addition to lots of blood work. And then you titrate the carbohydrates down over about four weeks and we find we have better compliance, better adherents, and then people are just not and also less side effects, because if you rapidly induce someone into into keytosis with you know, if they're on a low fat diet and they go to eating like seventy eighty percent fat, that can that can cause some side effects from fat and tolerance. So a gradual approach,...

...just reducing carbohydrates from like two three hundred grams a day, which is like kind of normal for the standard American Diet, down to a hundred per day, produces a really nice effect on Glucose and insulin and you become more metabolically flexible. You know, that defined as being able to use all fuel sources. You know, fat, Keytones, glucose and you know it, and that as you become more fat adapted, it's easier to transition someone from a lower carb diet into a state of keytosis, like nutritional keytosis, where you have pretty profound suppression of the Hormone Insulin. Your glycemic variability, if you look at it, your continuous glucose monitor trace roughout the day, it's essentially flat, much, much different than what you get with the standard American Diet. And you know, we don't know if reducing fluctuations in Glucose in non day of people will have long lasting benefits if you do this all the time, but you get a hunch that it will because if you look at the data for type to diabetics and type one diabetics, the wild postprandial glycemics, excursions, if you want to call that, are directly correlated with like longevity. Right. It's like the more your you have these wild glucose fluctuations, highs and lows. You know too you can go too low if your type one diabetic, especially if you're adminished during insulin, then that becomes a problem. So we're of the opinion that if you can manage your blood glucose within certain parameters, you're also managing insulin and you're optimizing your metabolic health and that's going to pay big dividends you know, as we age and we're decreasing inflammation or decreasing glycation, were improving a whole host of metabolic bio markers that are tightly coupled with, you know, healthy aging and health span. But the data is not you there's not a whole lot of data using these continuous glucose monitoring devices and non diabetics. So that's I'm pretty heavily involved in that research now. I love ctms and we talked about it all the time on the shows and yes, I'm definitely team CDM. What are your thoughts on people who are doing ketogenic diets but they don't experience the swings as much, but they experience higher resting blood sugar levels than they might be otherwise? We don't see this that much with our current group of people, are current cohort, I think because we're transitioning them and I think that might it might be helpful to transition them. My views of that have changed a little bit. I think it definitely for compliance and and people do get side effects when they follow caject Diet. So I'm of the opinion now, if you're not doing it for epilepsy, of course, where you need to get rapid seizure control to kind of ease into it more. My thoughts about that have have changed. So the dawn effect. And The dawn effect is sort of when towards in the morning, before we wake up, and especially it's like as soon as we wake up, we get a pulse of Cortisol which usually peaks in the morning and the body is wants to be primed for, you know, the taking on the day, whether that be physical or connect a task, and it's a bit of a stress response, you know, when you wake up. So glucagone, which is the counter regulatory hormone of insulin, can be elevated and cortisols higher, also in the morning, and that can contribute to Galcogenalysis, which is the breakdown and Glankogen for glucose in the liver. So we tend to see in some people, especially if they've eaten like a lot of food at night or carves at night and they have maybe higher glycogen stores in the liver, they'll have this this sort of spiking and in some people it's higher and and other people they don't see it as much, but I would say about more than fifty percent of people do see a morning elevation in glucose, but it typically we'll taper off during the course of the day. I mean I've been looking at dozens, if not hundreds, of CGM traces and I do see this, this elevation of a baseline insulin in the morning, or basine glucose rather, in the morning, but the insulin levels go down. So if your insulin levels are down, then the insulin helps to facilitate glucose disposal right and if your insulin levels are suppressed, then you know, more of that glucose may may float around in circulation, but it's still within sort of physiological ranges. You know, typically not. I think the important thing is like it. You want to look at it over the course of the whole day. You know, and generally speaking, if you look at average glucose levels on acutogenic diet, it goes down, or hemoglobin, a one see, will go down. Surprising, glucose is not good at zero because we have all these counter regulatory mechanisms to maintain homeostatic mechanisms to maintain blood glucose and some tissues and cells like the Red Blood Cells, need glucose.

So we have and then we can make glucose from the glycerol backbone of triglycerides and some immuno acids can make glucose to so glucose levels unless we really restrict total calories or we do things like intermitten fasting and that can bring it down. You know, over time glucose levels don't change a whole lot on a eucoloric ketogenic diet and in some people they may trend up in the beginning, but they will typically if you have someone who's type to diabetic and hyperglycemia, those typically comes down. So it may be a case where, especially with people not having as much access to things like C GM's until now, where this idea that the higher resting blood sugar is happening on Ketogenic diets might be more that people historically on Keto giets we're doing a finger prick, you know, just getting a snapshot a few times a day rather than getting the whole picture. Yeah, for our current like cohort what we encourage it and we just had another meeting about this and I talked to a bunch of investigators doing, you know, low carb Q Jank Diet Studies. They have them measure glucose before dinner, like later that day and kind of a semi fasted state before dinner, and then that's kind of a better way to go about doing telling yeah, the thing is it to measure it, you know, at the same time every day and multiple times throughout the day. I think it's going to be important, you know, because these things change, like true. Triglycerides fluctuate throughout the day. Hormones fluctuate throughout the day. If your glucose bumps up a little bit high in the morning, if you start a key chank diet, it's might be lower in the afternoon, as it was with me, like I'm usually like in the s in the afternoon and like low s and s throughout most of the day in the afternoon after twelve. Have you done any studies on cryotherapy and how it affects blood sugar and keytones? I use the hot at home. I get finally got my hot TUB. We have this like old, ancient like pool concrete structure and I got the hot tub and I tweaked it so it goes higher than normal instead of one or four which would so I cant therapy and I noticed my CGM gets a big spike. But the sensor in the CGM, if you heat it up, it's going to give you a positive effect. And then I jump into the pool water, which is pretty cold, and I go back and forth and I noticed when I jump in the water I wear a dexcomon. I can't turn the alarm off the thing. The alarm goes off like crazy all the time. When I go in the pool and I come out the things being like crazy every single time. So I think that's more of a sensor anomally, because if I prick my finger in check, I do have lower glucose when I switch back and forth. So you're specifically talking about cryotherapy. So going in cold water kind of does the same thing because it's bringing your core temperature down to and if I do heat therapy and I bring my core temperature up, the nice effect I see from that is that it lowers my blood pressure when I get out. I've been doing a lot of blood pressure measurements. But the cold therapy will stimulate what's called your catacola means, like your dopamine epenefer in nor EP and Fern, and by stimulating catcolamines you do two things. You're facilitating more fat burning effect. You know, adrenaline will liberate fat from Adipose, so you'll burn more fat, but you will also you might increase your glucose levels because adrenaline will stimulate glycogenalysis, which is the breakdown of of Glycogen for Glucose. So as a stress response, you might see that. That was the reason I was asking because we were talking about spikes and then I do ac cry out therapy almost every day. I did some before this actually, and when I'm wearing a CGM its spikes so high I didn't know if it was actually from the Cryo or if it was from the sensor freaking out. But after it would go down and then ultimately go to lower levels than pre cry oh and stay lower throughout the rest of the day. So yeah, it could be just your sympathetic nerve system activation from the Cryo, depending on how how low that is. But the sensor does you can the sensors operate within a particular range, temperature range. So to test that you could just sprick your finger and use something like an avid precision extra or the Keto Mojo device and then measure your blood glucose and keytones. To and see Blu Glucose to see to check your sensor. So when I put the sensor on, it's always running high relative to my fingerpric device. So then I usually kept the calibrate it. But then I calibrate it so it's about five points over. I have to bring it down because usually like ten or fifteen points high relative to my finger prick device for me. But I usually calibrate so it runs a little bit high so I'm not getting these alarms all the time for local ghost which happens quite often. If you oh que jective, that would make sense. That's smart, that's funny.

Okay. So stepping back a little for a bigger picture of I love the question why, and I have a lot of why questions about why the body does ketosis and creates keytnes. And one of the biggest epiphanies I had recently, and you can tell me if I'm correct with this, but people often think that the reason the body enters ketosis is because we run out of glucose. So we don't have energy because we don't have glucose, so we have to make key tones, basically that we need to access our fat, and so that's why we create keytones. But my new understanding is that we're always probably burning fat with carbs in the creb cycle and the reason we enter Ketosis isn't because when we run out of CARBS, isn't because we don't have carbs to burn, it's because we can no longer burn fat because we don't have carbs to burn fat. Is that correct, because that was like a mindblown moment for me. Well, to biochemically, what happens is you are the simplest way to explain it is that when you enter state of Keytosis, whether it be fast and keytosis or the Ketogenic Diet, through the Beta oxidation of fats are so high in the liver, you accumulate Aceetal Coa and the accumulation of Aceetal Cooa gets directed into the path of key to genesis, where two PSEUTAL COA molecules will condense endomatically to what's called the CETOACETATE, and that's a key tone body and then through another enzyme, DC to actate, can convert to Beta hydroxybuter rate, which is another keytone, and then they both enter circulation and in the blood. It's an about a three to one, three to one or four to one ratio by a hydroxubeuterrate to a setolas state. But the reason that happens that your body makes keytones is it's well to preserve energy flow to the brain. That's probably the evolutionary reason why. But biochemically what's happens is that the level of Beta oxidation of fatty acids in the liver is so high you got to do something with the Acetal Coa and the crib cycle gets a bit backed up and and the a setal Coa then gets condensed and forms goes down the keytogenesis path. and that's almost entirely dependent upon the suppression of the Hormone Insulin. So if you were to get even just a little bit of sugar or anything that increases insulin, insulin can quickly insulins a storage hormone, and you go quickly from a catabolic state, fat catalogic state primarily, to an anibolic state. And so if you're fasting, for example, and you you're in a high state of Ketosis and you inject the hormone insulin, it kind of can cause a dangerous scenario where your your keytones will start to come down after a period of time. You probably be protected from the hypoglycemia and that has been shown in some early work. But that production of keytnes is primarily a result of the lowering of the hormone insulin and that stimulates your fat burning so much so keytones are a really good indicator that you are burning fat. So in that case you know Atkins was right. Like you know you, you get your keytones elevated and you and you know your your body is in a fat burning state. You can't make keytnes without burning excess fat. That's that's a statement that no metabolic physiologists would argue with. So to clarify, so the ASETO COOA building up in the liver is coming from fat stores on our body or our diet? Yes, Yep, are when we fast or we go into a state of keytosis, whether it be diet or fasting, then you're getting fatty acids to the liver. You know, through your adipose your you activate, for example, if your sympathetic nervous system is activated, it can activate hormone sensitive light pays and then the adipose tissue or like cells that that contain the fat right, and then you're liberating the fatty acids, the trigly strides of fatty ass from your system and these fats go in circulation and the fats are an amazing source of fuel for skeletal muscle. The heart preferentially burns fat for energy. The liver, you know, relies on fat for energy, many organs systems do. But the long chain fatty acids that are typically dietary and the facts that are stored in adipose do not readily cross the blood brain barrier. So what happens is that these long chain fats are broken down through a process called Beta oxidation, and too their constituent molecule, which ultimately is Acetal Coa. And then the ACETYL COA is a breakdown product of fat, which is occurring at a very high...

...rate in the liver. The liver is chalk full of Mitochondria and there's just like massive fat oxidation the liver. Interestingly, the liver cannot use key tones as an energy source. So the the key tones that are produced in the liver gets spilled into circulation and then they become fuel, most importantly for the central nervous system, but also the heart so if a person was actually starving and did not have excess body fat, what they stopped being Ketogenic, because they won't have the fat to create the Keytnes, I guess, and they won't have any fuel. But, like, would there be a level where they're just burning the fat to run their metabolism and they wouldn't actually go through the KETOGENIC process? There is. You know, even a lean person has a really high amount of energy stored as fat. Like I mean you have to get towards you know, contest body builder, which is becomes dangerous when you're tapping into your essential fat right you get down to like two or three percent, which is extremely rare. You know, only in starvation effects do we see that, or people who are manipulating it chronically to achieve certain body composition alterations associated with, you know, bodybuilding, or and the use of bodybuilding drugs and stuff to to achieve that. So it's unlikely that you'll ever, you know, lower your body fat so low that body fat won't be available to to make keytnes. So it becomes really rare. I mean it happens in extreme athletics things like that, but it's for the normal person, for nine nine point nine percent of population that that's not going to happen. We do have a variety of you know, people have. There's different disorders where you can enter a state of keytosis. So some people are better than others. There's like, I think, like thirty different enzymes associated with Beta oxidation of fatty acids and keytogenesis. There's Beta oxidation defects where if someone fast they literally can't make keytones and then they can go into a seizure. There's Carne teine deficiency syndrome, CPT one, CPTTWO. There's medium chain acid deficiency syndrome, which is called M Chad. Then there's l chat and s Chad, which is long chain fat. There's a lot of different metabolic disorders that, you know, we teach and and there's various disorders where that are contraindications, where people would not want to do a keytogenic diet. It can actually be deadly with someone with a cpt one or carnatine deficiency or something like that, or even Beta oxidation defects, so they have to be on a high carb Diet. These are rare disorders, but it happens and I think it's also on a spectrum. Like we may have some snips where we may not make as much you know, certain fatty acid oxidation enzymes as the next person, and that that's that could be the person who just does not feel well on a Ketogenic Diet. And then there's a variety of different, you know enzymes too that are associated with the keytogenesis process and in some people can quickly get their keytones elevated and other people just cannot seem to get their keytones elevated as high, and that could be a consequence of the bodies just using the keytones for fuel, so they're cleared from the blood and they're not really picking it up. But you know, you could have like thilase deficiency, which is one of the keytogenesis enzymes. It's you know, that's a potential disorder contributing that. But these are kind of rare, or their thought of as being rare, but I do believe that people have, you know, it kind of like it's not an on or off thing. I think we have varying levels of these and but I do think we can train our metabolism to be a better fat metabolizer, a better key tone producer and a better key tone utilizer. Simply by putting our body into a state of high fat oxidation and Keytosis is actually changing the transporters, where the monocarboxylic acid transporters, which gets the key tones across blood brain barrier, across cell membranes and across mitochondrial membranes, were stimulating in an even an epigenetic way, the the production of keytolytic enzymes, the enzymes responsible of basically converting keytones into our our energy currency ATP so we can, we can do that. So so when we when we when we just dial back the carbohydrates, that's actually increasing our fat oxidation. And then when we we become keytogenic, then a whole slew of metabolic processes occur, including the increased production of proteins that actually become, you know, transporters and keytolytic enzymes can be elevated. So this is all. I'm kind of referencing animal studies, but we're that's why I you know, studies are ongoing now taking muscle biopsies and there might be the adaptation may be different in some people and it might be different in the liver, it might be...

...different in the calf muscle verse, like you know, the Bi Sep or the lack or something. There's probably tissue specific alterations that cur the cur to that we need to appreciate. What do you think are the implications of is it the inuit that actually don't? They have a genetic predisposition to not intererketosis despite being on a low carb, I fad diet. There's different genetic predispositions for some people. That essentially happens is that they're very good at Lucinia Genesis, so they can convert more gluciniogenic amino acids like alone into glucose. And I don't know if someone is done really a comprehensive study to show that in the inuit or basically carnivores but eating whale blubber and seal fat and things like that, and it's pretty close to a ketogenic diet, but probably not even as high as in fat as a classical Ketogenic Diet. But yeah, I think they have evolved to basically convert protein and maybe even the glyceral backbone of triglis rides into more glucose and that they become insulin resistant if you if you put them on higher carbohydrate diet. So they have a just as American Indians, do you know they have a predisposition for type two diabetes. I brought that up because I've heard that use as an argument to say our bodies don't want to be in long term ketosis because if you look like this population that historically would have been on a long term Keto Diet, they adapted genetically to not do that. Yeah, so basically I just heard that argument. I don't know if you have thoughts that about that. I would argue that the still be, yes, still be in a mild state of keutosis. And you know even you know in from the Ketogenic Diet Literature, even the people who study it that are big advocates for the Ketogenic Diet will say that a medical ketogenic diet is not natural and it's not a healthy diet. Like they will say that right up front, like the leaders at Johns Hopkins, for example, Dr Rikossoff and Mackenzie Servenka. You know they that's, I think, a quote out of the book. But at the same time that diet is optimal and super healthy for someone with epileps here I because it's controlling that condition without drugs. And then now there's modified variance, which the Hopkins crew has really spearheaded, the modified ketogenic diet, which has more protein and allows for more fiber and a little more liberal with carbohydrates and things like that. And you know, you have the spectrum of Ketogenic diets. would be the five to one keytogenic diet, which is like over ninety percent fat, to the modified Atkins Diet, or the low glycemic index diet, which is a one to one ratio, one being in grams fat and the other one would be in grahams, protein carbohydrates. And if you work out the ratios, it's like, you know, like sixty seventy percent fat or something like that, but it just allows for more fiberus carbohydrates and a more liberal with protein. So I would argue that, you know, a keytogenic Diet that was used clinically, a classical keytrogenic diet, is really so high in fat. I don't very few, you know, only very limited geographic regions, would people follow a diet that was truly ketogenic. So chronic keytosis is probably not ideal when when you're following like a medical ketogenic diet. It might not be optimal and I guess the question is, is it healthy? You know, if we look at the community of patients that had to follow it, like glucose transported deficiency, and then there's also people with Epilepsi who have been on it for up to three decades, their blood work and they're like carotted arteries and everything look fine and it look great. So you would think that, you know, we demonize saturated fat and high fat diets and stuff and there's very few people that are that don't have epilepsy that follow the Kud it, but there are people that truly follow a medical keytogeneic diet which is extremely high and fat and they've been following for decades and their blood work looks remarkably great. So one could argue that that's pretty good. There is a couple studies actually that shows the distensibility of the arterials are a little bit reduced in some kids that follow the Ketogenic Diet and then when they get off the Ketogenic Diet that distensibility comes back. So, you know, I think that's kind of people will point to that data, but I think it's kind of weak. Also, some of the earlier studies with the kittajank Diet and kids showed their triglycerides go up really high and lbl. But these early diets were basically like hydrogenated soybean oil mixed with like caseine and and you know, our knowledge of the keytogenic Diet went from just it, just from a macronutrient ratio. I mean literally it was like Chrisco, like the the majority fat would be Chrisco,...

...like hydrogen age fats and thin so our knowledge of the types of fats has dramatically increased over time and we know that. You know, switching out some mono when Satura is switching out saturated with more mono when saturated and getting more of a balanced fatty acid profile can have pretty big effects and improving lipid profile. So speaking to that, so the dietary fat and then also looping it in with what you were talking about with, in a way, teaching our Mitochondria to burn fat. Is there a difference in quote, teaching our Mitochondria to burn fat in just from going low carbs, so like not really adding fats, so them just burning in dodginess fat compared to actually taking in fat? Does that like teach the Mitochondria to burn fat faster. Yeah, for it's like adapting metabolically to Burnie fat when we were strict carbohydrates. Then the process to make energy that's independent of the Mitochondria is glycolysis. And there's a reduction in glycolysis and sugar metabolism for a number of reasons. One, you're just limiting glucose availability, so glycolysis goes down and when you lower the hormone insulin, that hormone is really the driver of glycolysis. So so the metabolism of sugar, which is independent, which occurs in the site as all, independent of the Mitochondria, goes down. So the Mitochondria are stressed and actually can in the beginning create some oxidative stress and the Mitochondria need to adapt to make energy to compensate, so that you get a little bit of an energetic crisis which triggers a robust increase in mitochondrial function and also mitochondrial biogenesis. And we know that chronic calorie restriction can increase the number of Mitochondria and we call that mitochondrial biogenesis. And then over time the Mitochondria become more efficient, which in regard to their energy production, relative to their reactive oxygen species production. So when we burn energy, some of the exhaust of the energy, so to speak, is reactive oxygen species or oxygen free radicals. In the Mitochondria, the primary one is superoxide and then that can go to hydrogen peroxide and then more reactive intermediates like hydroxyl radical and that can oxidize membrane lipids, proteins and nucleic acids. But when we follow a ketogenic diet or calorie restriction, we first stimulate the METOCON, it becomes a mitochondrial stress and then, you know, maybe the word hormesis comes in here, where it's a hormetic effect, where there's an adaptation to the chronically low levels of glycolysis in the adaptation produces more energy through something called oxidatid phosphorylation, which is exclusively dependent upon the Mitochondria. So under normal conditions, like the skeleton muscle, I think, derives about eighty to ninety percent of its ATP from the Mitochondria. But like a cancer cell, for example, has defective mitochondrial function in regards to energy production, so will default back to sugar metabolism for energy but also for biosynthetic processes. So, like cancer cells may rely almost eighty to ninety percent off sugar metabolism independent of the Mitochondria, and so this there's there's, you know, big, big differences in mitochondrial function and mitochondrial health. Healthy Mitochondria help to keep the energy status of the cell very high. And if you have chronic damage to the Mitochondria, the nucleus sense is that there's an energetic stress and that energetic and that that energetic stress perceived by the nucleus could may also be associated with excess reactive auction species and that could potentially kick on oncogenes and transform a normal cell to cancer cell. Like under certain conditions, for example, you know, if you drink alcohol a high concentrations and you're hammering your liver with alcohol, a little bit of alcohol can have a hormetic effect and be very healthy, healthy and beneficial. But like chronic consumption of a toxin can damage the Mitochondria and Mitochondria senses in energetic crisis and it's the dam it's from that that actually can kick on, can to transform a normal cell into a cancer cell, and that cancer cell has a widely different metabolism well to the healthy cells. I just finished reading Dr Steven Gundry's new book called cracking the Keyto Code, and his thesis about Keyte and Keytnes and the Mitochondria is that keytones are not a super fuel, they're not efficient. It's not about how they quote burn cleanly that it's basically all about how they do part...

...of what you're just talking about with stimulating the Mitochondria to create more Mitochondria. Like it. His whole thesis is about Mitochondria uncoupling. To what extent is the role of key tones in our Mitochondria about encouraging the Mitochondria to one couple and create energy that way, versus the keytones themselves being a fuel source? Well, we need to appreciate keytne bodies, but Beta hydroxybuttery ANCY, to ask a Benadroxybuttery is a very good energetic fuel. So that's why, in a fasting state, keytones become the primary source of energy for the brain and early work done in different model systems, for example the working heart preparation work done by Dr Richard Veach, had trained under Han's crib and did a lot of work in cardiovascular system and on the energetic effects of keytone bodies. And when you metabolize as keytones as an energy source in the Mitochondria, it produces a favorable energetic profile relative to glucose. Biochemical terms, the Delta G of ATP HYDROLYSIS is higher for Keytones relative to Glucose. So in a working heart preparation what that translates to is about a twenty five percent increase in the hydraulic efficiency of the heart if you're burning keytones relative to glucose. So this is I mean, this is wellknown. I don't know he knows about that, but we know that this is well known. In the heart a little bit hard to do a working brain preparation. Working Heart preparations a little bit easier experimentally. I can tell you from if you take keytnes and give them two cells, you know, and then you remove glucose, normal healthy cells with good mitochondria can function in the absence of glucose, which is really remarkable. Right. If you have cancer cells and you're growing cancer cells with glucose and key tones and then you remove the glucose and leave the keytones, all the cancer cells die. So at least the brain cancer cell lines that have that. People look at. Some cancer cells May Bee metabolically flexible to use keytnes as an energy source or biosynthetic fuel, but as cancer becomes more aggressive, it's sort of defaults to a more glycolitic phenotype and not only relies on glucose, it needs high levels of glucose to stain life. You know, I we believe, I think the field at large kind of believes, that keytones are superior energy source in many ways in regards to producing ATP with a less reactive oxygen species production. So that that is pretty much wellknown, at least in the heart and in other tissues to but keytone bodies are also powerful signaling molecules that can change the activation and expression of different enzymes called histone dacetallase enzymes. So they can function through histone dacetallase inhibition and that can actually activate genes and hold gene programs which confer protection to cells, and it can actually upregulate and dodges antioxyd enzymes like superoxyd dismy tase can be increased and catalase, which are enzymes that have in dodges antioxidant function. We also a project in the lab that we're working on now that is a PhD dissertation project is actually looking at the direct effect of keytnes on the his stones, which are basically his stones can prevent the activation of certain genes and through interaction of Beta Hydroxy buttery with the his stone, it can actually activate different gene pathways. And we're actually looking at keytone bodies as epigenetic regulators for certain diseases, is one of them being Kabuki Syndrome. So yeah, keytones have a wide there's a key tone receptor, the GPR one or nine. A receptor is a receptor for for keytone bodies. keytones have a plethora of different signaling effects that we're just starting to understand. The literature is pretty nascent on this and, as we understand more pharma circle companies are becoming increasingly interested, especially in the ability of certain keytone bodies like Beta hydroxy bettery, to inhibit inflammatory pathways. There was a paper published in nature medicine showing that Beta Hydroxy bettery can suppress the NLRPTHREE inflamazone. When that signal protein complex gets activated, that sets off a cite a kind storm and in an activation and elevation of things like Isle One, Beta, TNF Alpha and I'Le Six and things like that, it's thought that the effects of fasting and the elevation of Beta hydroxy better eate. It's that elevation of Beta hydroxybewer eight that contributes too much of the anti inflammatory effects of...

...fasting. Yeah, I'm interviewing him on Monday and he basically tries to dismantle everything that you just said about keytones. You know their role actually as a fuel and their benefits, and he just focuses on that, the signaling aspect of them, and how that's really what's going on. So rather than it being additive, he makes it like this is what's actually happening. So this this is helpful. Well, I think it's. Yeah, I mean I'll have the the look at his book, but I mean we've known, for example, the early work by Dr George Cahill from Harvard Medical School, where they fasted subjects for an extended period of time, forty days, and they injected them with Insulin to rapidly lower blood glucose, and the subjects were asymptomatic for hypoglycemia because their keytone bodies were elevated in their blood. So if keytones were not functioning as a remarkable alternative energy substrates, substrate, all those subjects would have died. So that you can't live if your glucose is one millimolar and you don't have, you know, keytones elevated that your it's going to be universally fatal. So that was in one thousand nine hundred and sixty seven actually change some of the medical text books and because at that time we thought that the brain was exclusively dependent upon glucose and we knew that the levels of glucose largely remained relatively stable, even when you're fasting like it could drops down to like three millimolar. Maybe dips a little bit here and there, but one way to basically dispose of glucose and not make it available to the brain is to do an insulin shock, which is in the case of the KHILL study. They injected twenty I use of insulin which rapidly caused what would be fatal hypoglycemia. But because keytones were elevated and sustained at like about four or five millimolar, two subjects are asymptomatic for hypoglycemia and and this is really, really important, and when I read that, you know, I had to talk to him, I had to talk to Dr Vach and I realized that I would like to leverage exogen a key tones as a way to bring people back from hypoglycemic shock, you know, and that's it's kind of what what's happening to and diabetic keytoasidosis, and that's another thing that we could talk about. But the keytones, do you serve as a function to preserve their warning sign? Definitely, but yeah, but there's no doubt, I think every metabolic physiologist would agree that keytones are a very remarkable alternative energy substrate. LACTATE is to I think lactate is kind of under appreciated. I agree. Sorry, I'm fascinative. I lactate. I was too, and actually lactate was the before I focused on keytones. I focused on lactate because I was into mountain bike in and I used a product called cite amax and it had Alphae l polylactate and, you know, I became interested in lactate as a fuel is back in the early S, like one thousand nine hund ninety two. So it's kind of dating myself, but I was back, you know, in high school, got into mountain biking and I would go to the library and look up lactate as a fuel and then I became interested in administering exogenist lactate to protect the brain from hypoxia. If there was like stroke or brain injury or, you know, infants become hypoxic, you'd give them lactate. So that was like the original idea I became interested in and then somehow I and then I did some studies with lack tate, but I eventually got steered into keyto tones because it interested me that keytones could get elevated into millimolar concentrations. LACT tape too. But you have to exercise really hard to bring that up, and that that the Lactate, keytones and glucose are all super remarkable fuels for the brain and if anybody argues it against that then they're just they don't understand physiology. So it's interesting because one of the people he quotes, he quotes Oh and in Khill, one of their studies where they found that after a threeday fast, the muscles were using, switch using free fatty acids instead of the keytones. And so the argue muscles, yes, YEP, because you're sparing it for the brain. Okay, so that when it really apply to the know that the keytones are for the brain. Really, I think you know muscles are incredibly metabolically flexible. So you know, you get into a state of keytosis and then your muscles will start using keytones. But it's like we got it, we got to spare these keytones for the brain. The muscles are incredibly hungry for fatty acids, to for fat as fuel. But yet it's like that. It's really, evolutionarily speaking, it's the keytones. Really their primary focus is to preserve the central nervous system and to make it so we are lucid, that we have brain energy so we can go forge for food and resources in the face of starvation. That's why we were able to live. Dr Stephen Kunine wrote a great book on this. It's called survival of the fattest, or fat it's he would be a great...

...person to have on. He has a whole book on the evolution of fat as a fuel for human metabolism. I didn't actually read the article, but I sought reference in an article that I was reading and it was saying that it's actually possible that the brain could fuel completely on keytones, but ethically we can never do studies to test that. Do you have any thoughts on that? I don't believe that's the K I think glucose is so such a ubiquitous fuel and we have so many the homeostatic mechanisms that our body has to maintain glucose levels are very, very robust and that's why we can fast for forty days and our glucose is still like two or three million molar and that's that's a significant amount of energy in the blood. But yeah, so I would I get ask that question a lot. Could you know the keytones be the hundred percent fuel? And I think there's certain organ systems to think maybe the kidneys, and maybe maybe there's organs that probably need a certain percentage of fuel. Red Blood Cells. They don't have Mitochondria because it makes them a little bit small. If they had mitochondria, they'd be bigger and they wouldn't be able to get into the little, you know, tiny nooks and cranny blood vessels where they need to get to so they leverage exclusively glycolysis for their energy systems. So if we went to Zero Glucose, I think it would be toxic to the body and a good example that there are drugs that are trying to mimic the Ketogenic Diet and one is too deoxy glucose, and that inhibits glycolysis and it becomes cardiotoxic. If once you increase the dose, unfortunately the dose that becomes a very effective dose for controlling seizures and also for inhibiting cancer growth. It then it then you get to the dose that becomes CARDIOTOXIC, although it's a useful tool, and I think it like twenty five milligrams per kilogram or something like that, if I remember correctly, has a pretty profound effect. But then you start when you're inhibiting glycolysis, you know that's not a good thing to do. And also chronic keytosis inhibits a rate limiting enzyme associated with glucose oxidation. That enzyme is pyruvate deadrogenase complex. So athletes, you know that are chronically doing keytosis when they go and do sprinting exercises or anaerobic you know exercise, they could be somewhat limited. Their glycoltic systems are compromised because they're inhibiting, you know, pyruvate deadrogenase complex. So it might be good to just, you know, I think, to bring that enzyme system back and to keep glycolytic flux functioning. Just keeping your you know, just adding a little bit of carbs in, like I typically do fifty to seventy five grams of carps today. Yesterday I probably did a hundred. We went to a Mexican restaurant. But I think adding some carbs in here and there is probably good for the person who's just doing ketogenic diet as a lifestyle. What are your thoughts on so that option? Option A, the ketogenic diet as a lifestyle with slightly more carbs versus super low car but doing the the cycling, so having like a carb upday. I think either option, it becomes very context dependent on what your goals are. The ketogenic Diet really shines in the context of color deficit. I think that if you're on a Keutajek Diet and trying to gain weight, like muscle I guess, or gain muscle size getting surplus amount of calories on a keytajank diet is probably not very good because it's going to be fat and you're probably going to back up in the liver. But if you were seeking to reduce your to lose weight, to lose fat as fast as possible and to retain your strength, I think there are advantages to a ketogenic diet for that context. And that becomes I mean, it seems like what a lot of people want to do right is like maybe they've gained some weight and they want to follow a dietary pattern and that could be, yeah, keytosis during the week. And maybe I don't like the idea of just carving up but I think to refeed carbohydrates with a calculated amount, likes maybe keeping fifty grams of carbs Monday through Friday but bumping it up to like a hundred fifty on the weekends or something like that, which I think I've done in the past, worked kind of well for me. So there's different ways to go about doing it, but it depends on your goals and I also encourage people to to measure, do blood work and in figure out what makes them feel good like and then measure then, like I remember testing the key to Jank Diet was like, man, today I feel really, really good and I will actually, you know, take measurements and it's like, okay, this is how I feel when my blow glucose is like this. And you know, before I was wearing a CGM and I follow the real strict key to Jank die and I just didn't feel well. I felt like a little bit of a headache, and then my keytones were higher like three or four. I was really strict and I realized that I had to be less strict with the Keytojenek diet and I was a little...

...bit more liberal with a protein and even adding back in some carbohydrates, mostly in the form of fiber like salads and some fibers vegetables, and then I felt better. But my keytones level dropped to like one million molar, which is really like the sweet spot for me where I think I'm getting the benefits of getting, you know, fiber in, which is probably good for your gut microbiome and got health, but but also, you know, adding more protein in, which I needed. When I first started experimenting with the Keyajank Diet. Is I had the book from Johns Hopkins so I was doing the medical keytjank diet to understand what it was all about, and then I migrated to the modified Atkins Diet, and then was started just formulating my own personalized key to Jank Diet based on my blood work and how I felt. Hi, friends, I'm about to tell you how you can get forty dollars off one of the most life changing revealing biohacking experiences that I have had. That would be the Nutri sense CGM program. 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It's helped me realize, for example, how low car versus low fat affect my blood sugar levels, how Berberine has an amazing effect at lowering my blood sugar and so much more so if you'd like to get a continuous glucose monitor, go to nutricence dot IO. Melanie. That's in Utri Sein Se dot Io melaniem Ela and ie and the cupon code Melanie Avalon will get you forty dollars off any subscription. That's nutricence dot Io Melanie with the Cube on Code Melanie Avalon, for forty dollars off any subscription. If you haven't tried a continuous glucose monitor, you are missing out. Now is the time and I'll put all this information in the show notes. All right. Now back to the show. Yeah, I have experienced that as well. So if I go very low carbon, even add in lots of MCTs, I can get my blood keytones up really high, but I feel much better actually doing intermitt fasting with a pretty high carbon take at night. I feel really good with that. But speaking to all of that, I'm so excited you brought this all up for people actually wanting to measure this, that you know there's so many options. There's well, there's not so many, there's so we can check blood keytones, breath keytones with acetone, urinary keytones. Can we walk through the three keytone bodies? And I guess I should clarify because I guess there's lots of different types of keytones right, but keytone bodies would be the three that we be looking at. Acetoacetate, BHB and Acetone. Yeah, Yep, and beach. Be's actually not a key tone. Oh it's not. Is it a transporter mechanism the physiologist to physiologists. Yet it's a key tone body. And but the keytone is basically like...

...a type of chemical bond between molecules, and there's keytnes sort of everywhere throughout the body. But when we're talking about the Ketogenic Diet, yes, it's right. That's primarily Beta hydroxy butter rate, acetoacetate and then acetone, which is a breakdown product of Acetoacetate. It can spontaneously what we call decarboxilee and lose a carbon and then becomes acetone. And Acetone is volatile, which means that, like when it's in solution, it gets into air, goes into the gas phase. So it tends we can blow it off in our breath. So traditionally we in epilepsy world, you're in, keytone measurements were used, and then blood keytone monitoring systems became available and and now I've been using a breath keytne device made my biosense or made by readout health, rather the company is read out health and in the product is biosense. I've had them on this sell yeah, yeah, and and there's and I was skeptical, very skeptical, especially the first couple units didn't work or the batteries running down. But then you know, I've used these things for years now and I feel breath as a tone really correlates with your fat oxidation state, and more so than Beta hydroxy beauttery, because if I'm sitting at my desk all day, like working and I'm fasting and I've done threeday fast and different versions of the key to Gye and things like that, my Beta hydroxy battery will be elevated. But then I start moving around and become active and I feel like I have very quick and robust tissue disposal. At hydroxy battery because you're using that as fuel. Ace atne not so much. So it tends to be a little bit more stable. And I noticed that I could taste acetone when I'm really in a deep state of keytosis and I know my body is just pulling off its fast doors, and then that's registering very high on the biosense device. But if I'm active and I'm in a calorie deficit, my tissues are sucking up the Beta hydroxybut rate for fuel. So it's not really showing on the meter as much as it should. And what I have learned over the years I see this in athletes like this. I just can't get into a state of Keytosis, but their bodies are so hungry, especially if they're in a calorie deficit, that the keytones are being sucked up into tissues and use as fuel. And especially if you're in a resting state. You know that's when your keytones were elevated, but if you're moving around and your metabolism is fast, there tends to be this disconnect over time. As you and then Peter at tea, I think, also reported this and we had an email kind of going back and forth, and we're like almost identical in the way our response is like, you know, Beta hydroxy beutter. Eight will start to come up and it'll be like one million molar and that will correlate two, three are that will correlate to ten aces or AC's. It'll they're reading on the biosense meter will be ten and that will correlate to one million molar. Beta hydroxy beutterate on the blood meter, but as you prolong you're fast, or if you're in a calorie deficit, the Acetote, my asstone levels went to a maxed out the meter to forty and it just it literally couldn't go any higher. And then my blood keytone levels were like the highest they got during like a threeday fast, or like two point two, two point five. I think couple times they bumped up, you know, because it fluctuates to like three or four, but largely, I mean they stayed, you know, they were there wasn't a tight correlation between Beta hydroxybuttery and breath ac a tone. And that's my interpretation and it might be more complex, but my simple interpretation is that my body was using the keytones for fuel because I could quickly lower Beta hydroxybuttery, which just some, some, you know, mild activity. I can see it drop down. I could be at my desk and I measure it and I'm like three and then I take a brisk walk just around the House and I'm back down the one with a brisk walk, whereas my ass tone levels will stay elevated, which makes sense because you're burning more fat. I also like the biosense device because I've literally taken thousands of measurements on it and that would have been thousands of strips, which would have been multiple thousands of dollars. So yeah, I've done many experiments and you can puff into this thing, you know many, many times throughout the day and then it goes into the APP, which is a great the APP is fantastic that they have for that device and it just becomes more cost effective because your key tones fluctuate dramatically. So you really need to measure like three to five times a day, three minimum five times a day to really get an overall picture of what's happening during the day in regards to Keytosis, and that that would be expensive and even painful if you're pricking your finger all the time, which I do anyway. But I think for people that just want a keytone monitoring system to as an index of their fat burning state,...

...and if they're I'll put it this way. You can't have elevated breath keytones and not be in a high state of fat burning. So I think it's reassuring to me to see that and rewarding, I guess, is the word to see that breath keytone so high because the carbons from that acetone are really were in the fat in your body. Acetone that you're blowing off is completely a result of fat from from your body or from your if you're fasting, or from dietary fat if you're eating. So what's actually happening? The Acetone, you said, is coming from the ACETO acetate in the blood stream. Yeah, in circulation. Be Hydroxy boutyrate is reduced and more stable in circulation, whereas a Cuto acetate. And we have to figure, you know, figure out resourceful ways to measure this because it can be kind of tricky and and acetones also very tricky to measure in the blood. But we've done it and we've published on it. So you your body's producing the hydroxybutary and Acetolactate in about a four to one or three to one ratio and that acetoacetate in circulation will spontaneously decarboxylate to acetone. And this is pretty it's pretty similar in in in everybody. Like I think most people have. I think physiology is met about physiologies in regards to this is pretty similar in most people, although I've across some people who just they don't they can't get anything on the meter and they claim that they're in Kytotosis. That was going to be my question, like does the environment the thing that makes me not nervous, but it's like if it's random, then isn't it sort of random? Like what causes it to create acetone? So yeah, I guess the word spontaneous. So it's spontaneously decarboxylating, but it occurs at a very stable rate all the time and there's a couple calculated a couple papers that look into this. So the the best estimate is about twenty percent. Twenty percent of the acetoacetate and in circulation will spontaneously decarbox late to acetone and then it makes its way to the lungs, which is a huge surface area. So we can pick it up in our breath and barely high concentration, you know, parked promillion, it's it's pretty high. So it becomes a very reliable, you know, means to to monitor keytosis and breath acetone not only correlates very high with fat oxidation, I became very interested in in in Acetone and we started measuring in the blood, although it's a tricky protocol to really get it reliably. But I saw I would became very interested in breath acetone because acetone correlated with seizure control and it seemed do. Is a lot of arguments about saying keytones don't correlate the seizure control, but the data with acetone seem pretty strong, stronger than the other keytone bodies. So I became very interested in acetone as a means to as a correlation for Anti sesure effects. So actually that that led us to developing keytone esters that elevated Beta hydroxybutury and Acetoacetate. So the one Keyton Ester that I've put a lot of time and effort into is one three buttane dial Acetoacetate di Ester. So you know that's a real long name, but when you ingest it it produces a one to one ratio of Beta hydroxybuury and a stoactate in the blood and then that acetoacetate spontaneously decarboxylates to acetone and then we get a blood measurement of acetone about one millimolar. And you know, if keytones get get up to like five millimolar and then that in that state that's incredibly anti sesure and your protective in that state. It at least in the model of auction toxicity, and then we tested a couple other models too, so it was important for us. I guess the message was it was important for us to not only elevate Beta hydroxybutyate but to also elevate acetoacetate to get the anti seizure effects, because it seemed to correlate very well with with acetone. So is the acetone in that case completely correlational or is it actually having any of the beneficial effects itself? Well, it's generally thought in the field that acetone is like a byproduct and we just blow it out and it doesn't really have a physiological effect. But there's paper showing that acetone can be incorporated to go back into like a CETAL COA and go into other biosynthetic processes, and I'm of the opinion that acetone affects many different things and probably probably the gating function of certain ion channels which play a role in excitability of cells like neurons. So yeah, like in particular, maybe a potassium channels. So I've been kind of interested in this and I don't I've got certain theories that are more speculation. But acetoacetate and bad hydroxyputerate are fantastic fuels and...

...they also have some interesting signaling effects. And Acetone was always this like thought of as this byproduct that we just blow off. But I'm of the opinion because of its high correlation with anti sesure effects, which is also could just point back to a CEO Astate, I think it has some biological function that's important for the things that we're studying and I'm trying to figure out figure that out. And well, there are studies showing that if you inject just small amounts of acetone it has anti sesure effects. So there's there's a direct, you know effect like Acetone, when it gets real high it will start to proce like a narcotic effect, but when you're on a Ketogenic Diet you have sub narcotic levels of acetone and there's still a strong anti sesure effect. So you're saying earlier how some people just don't seem to ever register the the acetone as much. Could they have high acetoacetate but not have high acetone? And then in that situation, and do you think they might not see the beneficial effects that they had seizures. That's a lot of hypotheticals. Yeah, I don't know. It would be well that the way to really answer this is to do metabolomics and I think, you know, we do have some metabolomics data. We're sitting on some some blood data. Now, I didn't got a lot of data engine didn't know how to make sense of it, but bioinformatics processing is improving, but I do in some ways. I think you know, we are a unique metabolic entity and we may have different metabolic response to the same ketogenic diet and I think it's going to be important to personalize low carb diets and keytogenic diets to not only our lifestyle but to our genetics. And we're not there yet, but I think different tools and technologies are emerging that will allow us to adjust our nutrition, which is the most important thing for our health. I think you know, I teach to the medical students and it's unfortunate that nutrition is not part of the medical curriculum per se, although we do have a course scholarly concentration nutrition, where we kind of get into the importance of nutrition, like for Health for lifestyle. It's like the biggest I mean we kind of all agree it's one of the most important things to keep people off drugs and out of the clinic right and the immense burden on our healthcare system is due to for nutrition or over nutrition. So I think it's going to be important to understand the utility of keytogenic diets and utility of just, you know, low carb diets and and to have tools to be able to personalize that. So the National Institutes of Health, they fund a lot of the you know, they fund nutrition research and their big focus, the federal government focus. They've actually are steering more money towards nutrition, but with a focus on personalizing nutrition. has been like the big thrust and we'll see where that goes, I think. I think it's a good thing to focus on, but I do think they should focus more on low carb diets and looking at the utility of low carb diets and directing more funding towards that well. Speaking to that, so the role of Diet versus exogenist key tones versus pharmaceuticals and things like that. Does the body know at all? So if they're like the key tones, does it know if they came from what you ate versus from exogenist key tones? And does it matter, or is it literally just once it's there, it's there? Well, good question. I was extremely skeptical about this idea of just like drinking key tones and then getting getting benefits. But I did study with immense enthusiasm the the keytone Ester literature, which was, you know, Dr Richard Veach and Dr Henery Brenning grabber and a few others, Dr Theodore Van Italy, George K Hill. You know, these are all just like icons and metabolic physiologies. There's not like a whole. There's not like really iconic metabolic physiologist. Now they're more like biochemist, but you really need to understand physiology to understand like the role of keytnes in metabolism. I think that, in your question is a good one. In regards to is it all just about the keytones? There are certain things that happen when we're fasting and go into keytosis, there are certain things that happen with a eucoloric Ketogenic Diet, as it means to produce keytosis, and then there are definitely things that happen when you ingest exogist keytnes, whether that be keytone Esters, and a lot of my research now is going towards keytone electrolyte salts. So having an electrolyte array that's beneficial to the body and those electrolytes are bound to key tones. So we're really formulating things now and the keytones salts and there's overlapping things, but this also distinct. Right. So when you're fasting you're in a calorie deficit and that produces...

...a coloric restriction effect. But interestingly the keytogenic Diet suppresses insulin and IGF one and some pathways that mimic coloric restriction. And then you have exogenist key tones which interestingly lower blood glucose. Keytne esters and high concentrations will will actually increase insulin. So I am of the opinion that that's probably not a good thing, unless you know medically the rise and insulince pretty small. But and you need a keytone Ester at a large dose. I try to double dose keytone salts and I don't I see only a little blip in my blood insulin. So and what are salts for successors? Just for listeners that are not familiar yeah, sure. So you can make a keytone Ester by taking keytone bodies and then binding them to a molecule with an Estra bond. Typically they're a couple. One is one three but tan dial, which is a molecule in and of itself. It converts to keytones. But you can take one three but Taine dial and then do a transesterification and then you can bind Beta hydroxy betery and a Cetol Acetate, either one to one three but Taine dial, and when you ingest that, it gets broken down in the gut and the liver and it releases the keytone bodies, Beta hydroxy bottery and a stactate, and then the one three but tane dial gets metabolized in the liver to Beta hydroxy bet rate. So that's that's a keytone Ester. You can also take glycerol and add a cutoastate or Beit Hydroxy beery to glycerol. So and then I'll produce a mild acidosis and actually it's able to get your keytones elevated higher. It's almost like a dose dependent effect. And then a keytone salt is actually we're taking an electro late like sodium potassium, calcium and magnesium. So these are electro lights and these will ionically bond to the keytones bit hydrox s beater rate. You can bind them to a CETOACETATE, but it's less stable. So they're not they're not very common. So you can have a sodium Beta hydroxy beterate salt, you could have a potassium Beta hydroxy beterate salt, calcium or a magnesium Beta hydroxy beeterate salt, and then you can put these in certain ratios. The formulation that we use is similar to the electrolyte formulation of the Product Element which Rob Wolf has. Okay, so, like I love that. I've had them on three times. Yeah, it's like one of the first things I drink when I get up, and maybe this is to his credit. Like we found that that electrolate ratio is actually the most tolerable in that specific ratio. So we bind the Beta hydroxy betery to the electrolytes in that ratio and then there's pretty tolerable and you can get levels up into like the one million molar and even to million molar range, and I think that's ideal. I you know, I have access to all different types of keytones. And I can elevate mine up to like ten million molar, but I feel sick, like I don't feel well once I get up to three or four or five million molar, but I do feel enhanced and optimized. So it's all about biohacking right. I do feel that I am like truly biohacking just by bumping my keytone levels up to about one to one point five with like a keytone salt, and you're also delivering electrolytes, which are probably a little bit deficient if you're low carb anyway, because you tend to excrete more electroltes if you're on a keytogenic diet or low carb. So that's that's my typical regiment. I take a couple servings of keytone salts per day and basically to deliver electrolytes and keytones at key times during the day. After this podcast I might go work out and I'll just have usually like a half a packet of keytone salts and I'll make some creatine in with that, and I do think there's some supplements to that are important with the keytogenic Diet, because we see it come up in blood work. Like Carna Tine. So I'll usually put some Carna Tine, a CDL Carna Tine, in with with the mix and drink that and that's a good zero sugar pre work out actually, especially with a little bit of caffeine. Could a person become keytone resistant, like they become insulin resistant, like the equivalent of having too much blood sugar all the time having too much keytones all the time? I would say no. I think the if you have robust mitochondrial health and metabolic activity, your body is going to be hungry for keytones what we see in sedentary people. If you do I like to call it a keytone tolerance test. If you take people who just don't exercise as much, like couch potato people, and you you have them in just keytnes, the keytones get elevated and they stay elevated in the blood a lot longer than someone who's an athlete. especially if you ingest the key tones and then get on a bike and ride or you do some kind of physical activity, those keytones get cleared very fast and elite level athletes. So it's just indicative of high key tone disposal into the...

...tissues were as a sedentary person would did not transport it as fast and that could be due, you know, the keytone transporter is a monocarboxyl gacid transporter, which may be up regulated athletes if they're making lactate, because it also co transports lactate. So yeah, we probably have much more robust keytone transport systems and keytolytic enzymes and people who are more metabolically flexible and adapted to key jank diets. So that actually speaks to because a lot of my listeners on the internted fasting podcast feel like they have to chase keytones, like they really want high keytone levels. And we were talking before this about how I was listening to Ronda Patrick on Joe Rogan and she was talking about doing keyto and really needing to keep eating fat to keep her keytone levels up. So is that something people need to be need to be doing? Yeah, run and I had that conversation. I'll be meeting with her next week and doing it put some podcast with her. Yeah, you do. A lot of people are chasing keytones and I don't. And you know, unless you're using it to manage a chronic disorder or something, I'm not of the opinion that everybody should be in a state of chronic keytosis. But say you're going to like pull the ketogenic trigger and do one one week out of a month of keytosis or modified fasting diet or fasting mimicking diet. You know, if Alter Longa, and it is, it is very remarkable in the day to kind of supports that. If you do that for one week out of a month, then you have this like extended benefits over a couple weeks. So theoretically, yeah, you can kind of follow I wouldn't follow any diet, but you can follow a more relaxed diet and then periodically go into keytosis. And you know, I tend to do a modified version of a ketogenic diet just because I feel I have higher productivity, higher more stable energy levels and I think there's a lot of health benefits. I incorporate a level carbohydrates that would typically maybe put most people out of Ketosis, like between a hundred to seventy five grams or day, but the cards are usually higher in fiber. But then I supplement keytones, you know, periodically throughout the day, just in a drink of keytone salts similar to the electrolytes you get from element or something like that. So I think of the salts have having two important functions of restoring electrolytes and just delivering a high energy source of fuel at the same time. And do you think people have any sort of metabolic memory, like if they've done a ketogenic diet once, is it easier to do it again? Yeah, yeah, I do. Yeah, that's an important point and I think just like muscle memory, when you build up and get to a certain strength or conditioning cardiovascular and you take time off, you can get back to that point, you know, like two or three times faster, and I think the same holds true if we train our metabolism to be a strong fat burner or keytone producer and we take time off. I know anecdotally we would hear people they would get into Coote keytosis much faster. I know I do by take time off, which I usually don't, but in in animal models we see this too. So if you put animals on a keutogenic diet and then take them off and then put them back back on again, the levels of keytone, keytones will be elevated quite faster, a lot faster. So so it's it seems that doing keytosis for a period of time makes the body more metabolically flexible. When you revisit that again, and you'll talk with to people who diet down for, you know, a contest or to make weight for a certain sport, and the first time they do it is kind of hard and the more they do it, and there could be a learning curve thing to this too, but I'm of the opinion that, you know, the more you do a Ketogenic Diet and the more you do low carb and train your body to burn fat, the easier gets and probably the more benefits you derive from it too, if you don't take it to extremes. Speaking of the the animals, I just finished reading the forever dog Dr Karen Becker. She's going to come on the show, but she talks in her book about the cancer retreat for dogs where they do a lot of studies with dogs and cancer and keytogenect diets. Yeah, I have that book. My wife is reading the book now and they have an amazing free ebook that you can just download and it tells you step by step on how to make the ideal food, you know, low car Kadjenek food for your dogs. Yeah, so a big fan of Karen Becker and the keytopet sanctuary and what they've done to really promote lowcar nutrition for for dog, especially dogs that have cancer. Right. So we know that it's a very powerful adge event, you know, when you add it the therapy and it could be a way to manage cancer...

...and reduce tumors eliminate them all together. You know, occasionally, you know there's when I got into studying the ketogenic diver cancer, there wasn't too many people. Thomas Seyfried was doing it, Dr Adrian check was doing it and there's a few clinical trials pediatric patients. But now if you go to clinical trialsteck of and just type in Ketogenic Diet and cancer, you get dozens of studies and you know, a new animal model study showed that there's checkpoint inhibitors. Ones PDONE and showed that the Ketogenic Diet can enhance sort of the the effects of some of these immune based drugs, to which is a whole new direction that I didn't think about toward until more recently. Yet a lot of potential for ketogenic diets in veterinary medicine and, you know, and expanding application for different types of cancer too. Are there some cancers that are likely to be exacerbated by a keygenect diet, like they'd say, like the tumors that fuel on keytones? There's no doubt that there's probably some cancers that would not be responsive. But when I think about a key jank diet, I don't think about, you know, starving the cancer of glucose or elevating keytnes as an IT. So when I think about a Ketogenic Diet for cancer management or as an Adje event, I think about it as suppressing the hormone, insulin, m TOR PI, three kinnees pathway. So I think of it as a way to change metabolic hormones that would marginalize and restrict tumor growth and then by, you know, limiting glucose availability, suppressing the hormone insulin and insulin related signaling and elevating keytones too, because they have, I think they do have, some anti cancer effects that can put, you know, put the brakes, or at least let the foot off the gas petal of cancer growth, and then the cancer becomes more vulnerable to other modalities that can kill cancer cells. And that could be chemo and radiation or immune based therapies like these p one inhibitors, checkpoint inhibitors, you know as a new area, and also the Pi Three kynees inhibitor drugs. Dr Luke Cantley has been researching drugs that target cancer metabolism, including pathree kynees inhibitors, and when we take these drugs they tend to have a counter regulatory effect and they increase these insulin unfortunately that was one of the side effects. But they these drugs work not so great in and of themselves, but when they're coupled and combined with the Ketogenic Diet, the Ketogenic Diet suppresses the hormone insulin and actually unleashes the therapeutic potential of Pi Three kindees inhibitors. So there's some evidence for that and and and that could be a new direction. So I view the Keytogenk Diet as a foundational sort of dietary approach that can be used for a wide variety of cancers and my original interest was to just use it for brain cancers, because people would brain tumors have seizures. So it made sense and I knew I communicate with patients that had a lot of side effects with anti epileptic drugs. So and then, as I started researching this topic, I stumbled a upon papers by Thomas Sayfried and Adrian check, and they would be great people to have on your podcast, that showed that they had these keytogenic diets had remarkable anticancer effects. And then that actually set off my enthusiasm for researching this. And then I had PhD student come along, Dr Angela Poff, and she was like, I want to do my peahd dissertation on this. So so the more research we did looking at keytogenic diets, keytone supplementation and also hyperbaric oxygen therapy, which seems to energize with the Ketogenic Diet, we saw remarkable effects in our model system. So it it's still we do quite a bit of research that we currently do is focused on cancer. So I have an idea for how pharmaceutical companies could turn this into a drug, sort of, sort of. Well, definitely for Keto from fasting, maybe Keto from Diet. They could make a pill and instead of all of the reasoning going into the actual makeups at the pill, it would all go into the instructions so, for example, you have to take this pill on an empty stomach with a certain eating window. That actually would be prescribing fasting. or it could be like for the Diet, they could say that you have to have this pill with this certain type of Diet. Yeah, so the EXOSGREN is key tones produce many of the the effects of, you know, keytogenic Diet. So they lower blood glucose remarkably low. So work done by Thomas Seyfried has have looked at the glucose keytone index and if we look at all the different cancer...

...studies that have been done in animal models and humans, the most beneficial effects seem to be achieved when you get the Lowest Glucose key tone index right. So what that translates to is the lower the glucose and the higher the key tones, the better that therapeutic effect that diet intervention had at restricting eliminating cancer, so cancer growth. So yeah, and a pill would do that. We know that a when you and just a ketone Ester or keytone salts, that you're lowering glucose and elevating key tones. And with the keytone salts, if the total rise in keytones are not above two millimolar. Then you're not increasing insulin, and I think that's going to be important too when we deliver. And then there may be drugs that could just stimulate fat oxidation and keytone production in the liver and there there's a couple drugs that may do that, but the drugs maybe have side effects. So I think that work needs to be done. But I do think I've actually I'm not going to name the pharmacutical companies, but I've traveled and went to a variety of different pharmascogul companies, like the more popular ones, and they they want me to give summary of the keytogenic dion all the mechanism so they can kind of make the keytogenic diet in a pill. And it's hard to do that because you know, the summary Slide is showing a dozen different mechanisms potentially working in synergy to produce the effects we see in the clinical endpoints right which is like lowering a blood glucose, reducing inflammation, having anti sesure effects. It's doing it through a variety of mechanisms. So it's going to be hard to make a drug that does that. I was thinking the pill could actually be a place bough. So the instructions for taking the pill. It would make the people fast. So they would think the pill was a pill, but actually it's just placebo and it would make them fast every day and then that could be the treatment. So the pill then would be like an appetite suppressant. That doesn't mean anything in the pill. It would just be like like has to be taken on empty stomach. It can't be taken within four hours of food either way, like taken the morning on an empty stomach and then wait like four hours eat. So then you're forcing people into a sixteen hour fast. That's that's a good idea. It's really good idea. Yeah, they don't figure it out, but yeah, there's I mean there are remarkable effects to placebos. Were just discussing this in one of my classes that, you know, the placebo pill. Yeah, and I also believe, just in following people over the years, you know, that if the the person implementing the approach truly truly believes that it's helping them, then it's more likely to help them. You know, and I don't I think there's like neuropsycho in Munology and you know, I know our brains can change our physiology and many, many hormone systems and things like. So I do believe there's a major effect belief in whatever you're doing. You know, if you believe that it's beneficial and having a therapeutic effect, it's more likely to work. I've just seen and enough patients that I've communicated with that that's the case and I think it goes above and beyond the science of what I know it should like I've seen. I've seen cancers kind of go into remission and like doctor saying, wow, this diet seems to be working and it in pretty much all cases the patient it was like completely convinced that it was going to going to help them. So just through the communications and you know, I guess there's of some where they believed it and it didn't help or but it just seems like the feedback that I'm getting like over the years that when patients really implement it and follow through and they believe it, then just you get these remarkable effects, therapeutic effects. Yeah, I just interviewed Shimani Jane. I think she wrote a bout called healing ourselves, and it was all all about this. Like the Biofield, science and the Pussy Buff Act, and she talks about studies looking at all of that and people's belief definitely plays a huge role. It does need to be study to and also when we get on a Chitogenic Diet or low carb or dietary intervention, ideally low car it's changing our psychology. So there's a whole field emerging called Metabolic Psychiatry, and Dr Christopher Palmer from Harvard was a speaker at the metabolic health summit and and we also have a number of speakers and are going to really increase this theme at the Metabolic Health Summit, which is like bringing together clinicians, basic science, researchers and companies to that support this kind of field, this idea that you know, there's not too many of. The tool boxes are not very good for things like bipolar disorder and depression, anxiety and things like that, and dietary interventions have very profound effects and they could be used as an adge event or maybe even, in...

...some cases, of standalone intervention for some people. So there's a lot of really cutting at red edge research going on right now for psychiatric conditions and using this dietary approach for that. What do you think the biggest barrier to like they're actually being a paradigm shift where conventional medicine is, you know, using these therapeutic dietary approaches more. I do think it's possible. Yeah, the big, the big purples. Implementation is hard. Most you know, doctors don't have a nutrition team. They don't have richistered Dietitians at their fingertip that can put patients on a Ketogenic Diet and make them comply and we don't know if they are complying. You know, you send them home with a diet, diet instructions of pamphlet or even have them go through a workshop to understand the Diet. But that's where I actually think. Continuous glucose monitors, or abbot came out with a lingo device or Lingo that measured glucose, keytones, lactate and alcohol. Oh really, I want that. Levels needs to make access to that. Yeah, the consumer electronics conference, the keynote was on that by the CEO of apple or CEO of Abbot Rather. Yeah, putting putting these monitoring devices on patients, sending them home so the data just goes to a cloud and actually you can just look and see if they're following the Diet or not. Yeah, it's going to be super important. It's going to be a game changer, I think. And then for them to you have an APP like you know the levels help APP. I use that, where they can just press a button and have access to a nutritionist and they and they can see the effect of a particular diet or amount of food on their glycemic response and they say okay, well, I shouldn't do that or I'll eat another eat another meal instead of that and they learn. It becomes very rewarding to them. They game a by the whole process and then it inspires them because they have more control over their condition. So I think these biowarables and these emerging technologies were there's multianalyte sensors, are going to be game changers for managing disorder, managing people with epilepsy or, you know, type two diabetes and other disorders where the key Jank diet is that therapy. It's going to be super important to monitor them to make sure they're complying, but also to optimize the approach. Just say Oh, you might add a little bit of fat or your keytones are actually too high. Maybe you can add a little bit more protein. To have that data is going to be really important. Hi, friends, so what I'm about to say may include some disturbing content, so if young ones are listening, you may want to skip ahead. On Valentine's Day, two thousand and twenty two, I experienced sexual battery by a man at a massage parlor. I felt so helpless and so scared while it was happening and afterwards I was really, really scared to tell anybody. I'm so glad that my friends encourage me to tell the police, and I'm so glad that the police believed me and that the man is now in jail. And ever since sharing my story, you guys have been so supportive. So many people have applauded me for telling the police, saying that something like that had happened to them too, and they never told anybody. I started looking into the statistics and they are pretty shocking. So sexual assaults are most likely the most prevalent crime in the US and they are also the most underreported. Every sixty eight seconds, an American is sexually assaulted. So I was one of those. Every nine minutes that victim is a child. Meanwhile, only twenty five out of every one tho perpetrators will end up in prison, and only five percent of sexual assault reports filed have ever been proven false. Eighty two percent of all juvenile sexual assault victims are female, ninety percent of adult rape victims are female, and in two thousand and nineteen over six hundred and fifty, two thousand, six hundred and seventy six women were raped and nearly one million women were victims of sexual assault. I believe this is a huge, huge problem happening in our society. It's one of the crimes where there's not usually evidence. It's not like a physical object was stolen or somebody outwardly injured or killed. It's basically your word against the perpetrator, and so it can be really, really scary to tell somebody and stand up for yourself, but I want to encourage you that we can change this, we can speak up. So if something happens to you, I encourage you. Please, please, tell somebody. I promise you you're not crazy. The thing that really convinced me to go to the police was it wasn't so much about me, but about stopping this man from doing this to somebody else. If you feel like someone crossed a boundary. They probably did. People don't usually question things that are appropriate and normal, and as parents, I encourage you to have these conversations with your children and whatever time and way you feel comfortable. I think we can make change here. It's just about spreading awareness and taking a stand and speaking out. So thank you everybody so much for the support. I love you all. You are amazing and let's change this. So, like I always say, you got this. Okay,...

...back to the show. Well, I am very excited and wow, thank you. This has been so, so amazing and for listeners, we even had to figure out for like half an hour before this we were having technical difficulties. So thank you so much for your time. I cannot thank you enough. I can't thank you enough for your work and all that you're doing is just really, really profound and life changing. Is there anything else you want to touch on? Any resources you want to put out there for listeners, anything else on your mind? No, I want to thank you for giving me this platform to speak and thank you for the invitation. I really appreciate is people like you that are getting the information out there and people are hearing it, and because you know, I do these podcasts and so many people, you know, respond back to me saying, Oh, I heard you on this and I started, I started doing this and yeah, it's really made a difference. So thank you for that. If people want to find out more about what I do, I have an informational website called kido nutrition dot org, keyto nutrition data work. People always ask me about, you know, what keytones supplement should I take in this and that? The one that I personally use is by audacious nutrition. It's called Ketostart and it's just an electrolyte formulation that's bound to keytones. So I like that. And Yeah, I'm a big advocate of using continuous glucose monitoring devices and and I think people could just, you know, sign up and just use it for four weeks and then that will give them like a ton of information. Like I wear mine all the time because I'm always testing things, but I'm a big advocate for that. And Oh, one last thing, because I get a lot of questions about diabetic ketoasidosis. Diabetic Ketoasidosis will not occur if you have, if you're not type one diabetic. So Diabetic Chuto astidosis occurs in the absence of insulin. So I just want to throw that out there because it's usually I get a lot of hands when I give toxic conferences and people are like, well, what about Diabetic Ketoastosis? So that becomes only a problem in the context of type one diabetes. But at the same time the key to journey diet is actually being used as a therapy now for type one diabetes, and you can look that up. There's like literature and studies going on and even a group that's advocating low carb diets for type one diabetes. This group is on a facebook group that goes by the name of type one grip. So my student, or former PhD student, Dr Andrew Koutnick, was a member of that and kind of network to that community d but it's kind of funny because when I used to give talks on Kid jank diets, I would say first and foremost, if you're type one diabetic, don't even think about you know this approach. But now low carb diets and kid jank diets are being used to manage type one diabetes, to reduce the amount of insulin that they need to manage their glucose within the tight ranges. So yeah, I field is changing a lot and I never thought that would happen. But we do have publications now supporting the use of these diets and type one diabetes community. Very exciting. So for listeners again, the show notes will be at Melanie avaloncom Dom Diegostino there. We a transcript there and I'll put links to everything we touched on. I'll put links to my interviews with levels and biosins and element and aura and faulter Longgo and all of that for people who want to learn more. I promise. This is the very last question. I ask every single guests on the show this question to end it, and it's just because I realize more and more each day how important mindset is. So what is something that you're grateful for? Oh man, so many things. Yeah, we had this discussion last night with friends. You know, I like to I do a gratitude practice every day and I like to focus on something like very, very specific every day and then gives me appreciation. So I'm just super there's many different things, but the health of my parents. So my parents are getting up in age and they'll be visiting very soon. So I'm super excited about that because haven't been able to see them with covid and other other issues. But yeah, I'm just really grateful for the health of my family and my friends who who also support the read the work that we do too. So I just I'm just trying to pick, you know, one thing. But as soon as I get off on this podcast, my wife is cooking dinner and I smell it now. So I'm grateful for the meal that she's cooking me right now and super grateful to enjoy the KATOGENIC meal I presume. Well, she doesn't meet Ketogenic, but dinner is usually pretty cutogenic. But I'm super grateful for the smell I'm smelling now and the meal. Never about the half together. So and the walk that we do with our dogs after the meal each night. I love that. Well, thank you so much, Tom this has been amazing. I so, so appreciate it. I will eagerly continue to follow all of your work and this just been amazing. So hopefully we can talk again the future and just thank you. I cannot thank you enough. I enjoyed it. Thank you for having me, Melonie. Thank you, bye bye. Thank you so much for listening to the Melanie Avalon biohacking podcast. For more information,...

...you can check out my book what when wine? Lose weight and feel great with galeo style meals, intermittent fasting and wine, as well as my blog, Melanie avaloncom. Feel free to contact me at podcast at Melanie Avaloncom and always remember you got this.

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