#825: Dr. Dominic D’Agostino — All Things Ketones, How to Protect the Brain and Boost Cognition, Sardine Fasting, Diet Rules, Revisiting Metformin and Melatonin, and More

0:00 Hello, boys and girls, ladies and germs. This is Tim Verris. Welcome to another episode where it is yet again my pleasure, after more than a decade, to deconstruct world class performers from all different disciplines to tease out The news you can use, the tactics, and specifics that you can apply to your own life. My guest today is a very popular and repeat. Guest on this show, Dr. Dominic d'Agostino. He is a tenured associate professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida, Morsani College of Medicine, and a visiting senior research scientist at the Institute for Human and Machine Cognition. He's also one hell of an athlete and if you were to ask me to name one person To ask any question related to ketosis

0:46 Exogenous ketones, in other words, supplemental ketones, anything at all related to the ketogenic diet, metabolic psychiatry, if I had to choose someone who is a decathlete of the highest order across all of those, it would be Dominic or Dom. He teaches medical neuroscience, physiology, nutrition, and neuropharmacology, and his research focuses on the development and testing of nutritional strategies. We'll talk about that, and metabolic based therapies for neurological disorders. Whether it's depression or chronic inflammation, cancer, and human performance optimization. He has served as a research investigator and crew member on NASA's extreme environment mission operations, and his research has been supported by the Office of Naval Research, the Department of Defense, the National Institutes of Health and Nonprofit Foundations among Others. We get into a lot in this episode. We get very much into the weeds. So I thought I would do something that I rarely do and just share a few of my takeaways. And these are just a small sampling, but I wanted to mention a few things. For instance, I have been taking various types of supplemental ketones, and they come in many different types.

1:53 You have ketone salts, sometimes combined with electrolytes, you have ketone esters of different types. They're Are many. different types of supplemental ketones that you can take. A ketone is not a ketone is not a ketone. And I learned, for instance, that if I am consuming something like ketostart, which is a ketone salt that also includes electrolytes, Or if I'm consuming, say, a mono ester or something like that, that I should add MCT oil to the mix, which you can get as an oil, or you can get it powdered. Now, why would you want to do such a thing? Well, straight from Dom, we had a lot of texts before and after this conversation, exogenous BHB. That's Beta hydroxybutrate plus MCT increases BHB higher than either one taken alone. MCT sustains the elevation of BHB salt and esters by slowing.

2:43 Absorption. So you want to take them together. The beta hydroxybutyrate is what is measured when you do, uh at least with Most devices a finger prick test for ketones. Now why should you care about ketones or the ketogenic diet at all? Let me give you a couple of reasons, and these are straight also from my notes with Dom from past and this conversation. So ketones are not just something your body produces. when you're on a ketogenic diet. Which was used for a very long time, a very long time ago for epileptic children.

3:15 You also run into ketosis if you're say in a starvation state where your body begins to pull from body fat and use that as fuel, which the brain and the heart love, for instance. But why should you care about them otherwise? Couple of reasons. If you think of some common neurodegenerative conditions, such as Alzheimer's, which is sometimes referred to as type three diabetes, you have an energy problem. And if your glucose, right, sugar, the carbohydrates, the normal stuff that people depend on, is compromised, you can sometimes circumvent that. and helped mitigate a lot of problems by using ketones. And ketones can furthermore be thought of as hormones in a sense, or at least signaling molecules. And so let me just read straight from my notes. So Dom explains that ketones are far more than just fuel, even though they are a really, really interesting fuel, especially if you're doing training like zone two training and so on. Citing a key paper he states that beta hydroxybutyrate, that's the BHB I mentioned before, is an H DAC class one and class two inhibitor. We won't get into that. It's histone deacetylase, but a pathway of great interest to the pharmaceutical industry for cancer therapy.

4:22 So what does this mean? By inhibiting these enzymes, ketones can activate genes that enhance the body's own antioxidant and cellular defense mechanisms. And Dom and I have talked at length in the past about the application of the ketogenic diet or ketones to different types of cancer. Dom goes on to describe a paper from colleagues at Yale. For whom Dom's Lab developed a diet protocol showing that ketones have a direct anti inflammatory effect. This is really important, and this is why I'm also paying so much attention to this. They were shown to inhibit a specific inflammosome. Okay, that's a word you should look up in flamazone linked to many chronic age related diseases, not just something like Alzheimer's. This effect was demonstrated to be completely independent of the ketone's role as a metabolic fuel. So it's a lot more than just an alternate fuel that you run into. when you say fast for a few days or go on a ketogenic diet or a fast mimicking diet. Other things we talk about. We talk about some risks of common

5:21 ketone supplements that are on the market. And I'm going to try to get the wording very carefully crafted here. And the way I'll put it is that There is potential for liver toxicity when certain types of supplemental ketones are used. Chronically. So I'm being very delicate in how I word that. But if you're taking anything with, say, one three butane dial based ketone esters, those are very, very common. Chances are if you get something at retail, or if you just search around casually and find something that it's based on one three butane dial in some fashion. If you use that chronically.

5:59 And not at super high doses either. Let's just say that's above a hundred milliliters a day. Now, if you're taking like high performance ketones and you're training as a cyclist, that's not actually a crazy amount. If you look at certain case studies where people have taken monoester for Alzheimer's, let's just say, in the hopes of mitigating symptoms. you get up to that level. So Got to be careful with the ketones that you are taking. And as always, cycling off on occasion and moderation, I think are the keys to success, as is true of so many other things. Otherwise. For instance, looking at the much

6:36 Touted and discuss. Metabolic zone. with respect to ketones. This can be done through fasting or the ketogenic diet, where you pull in something called the glucose ketone index, GKI. And uh sure, one to two might be ideal. One to five is still great. And uh what Dom and I discussed a little bit is that The Goldilocks amount of ketones, let's just call it 1.2 to 2 millimolars, and you measure that with fingerpricks, for instance, there are other ways to do it.

7:07 is anxiolytic. It reduces anxiety. But what I've noticed is that if I take a lot of exogenous ketones and have it spike far above that, then I actually have significantly increased anxiety. Row. Don't want that. And a subsequent crash, which may or may not be related to insulin and its effects on insulin. So let's look at a couple of other things. And I'll just emphasize again that some people are transitioning away from using one three butane dial. just a dialcohol and one three butane dial based ketone esters

7:40 because of these potential liver toxicity effects with chronic use. And that's gonna be coming out in publications in the not too distant future, I would expect. All right, looking at a few other things, some other usable tidbits. Dom explains that soluble fiber in foods like artichokes is fermented by gut bacteria into short chain fatty acids like butyrate, which are themselves ketogenic. So here's a little known fact that cows are naturally catotic due to this fermentation process. So when you're on the ketogenic diet, why not have some artichokes? There's one. And then I would say another Technology that I've implemented based on conversations with Dom is hyperbaric oxygen treatment, HBOT, H B O T. There's a lot of literature on this. There are a lot of fly by night kind of

8:27 bullshit operations out there. But if you're using a hard shell medical grade H bot facility that can get you up to let's just call it two point four or higher atmospheres ATA. Then you can apply it to all sorts of things. And I'm using it right now to hopefully enhance surgical recovery after elbow surgery. And uh one of the enhancements you can add to hyperbaric oxygen treatment is taking ketones beforehand. So taking supplemental ketones to reduce the potential

9:01 for oxygen toxicity and there are a host of other benefits. So Dom is, as I mentioned before, a real to cathlete across so many different fields that are touched. by ketones, by his knowledge of training. We even talk about, I believe, the use of Androgens or anabolic agents in cancer, believe it or not, which would be very counterintuitive, I think, to a lot of folks. We get into the weeds. So if you are listening, you're like Oh my God, I cannot make sense of all this terminology. Just skip ahead five minutes and chances are something will pop up that you can certainly apply. And

9:38 That is, I want to say, maybe the longest Intro I've done but I'm gonna make it just two minutes longer. 'Cause I noticed a few things that I've written down. One is that Dom is taken. a pretty substantial doses of melatonin nightly for ages, and I was always

9:54 concerned based on some animal studies showing endocrine disruption. And we discussed that. And long story short, I'm back on melatonin after having that conversation. And he also tells the story of Dr. Fred Hatfield and sardine fasting. So using one can of sardines per day. for a week of each month. which is very similar to in some respects the work of Valter Longo and the fast mimicking diet. But apparently, and I'm I'm pulling this from memory since I recorded all of this about it. few weeks ago that Fred was able to extend his

10:30 runway after a serious cancer diagnosis by years. Following this protocol, which was one week per month of what he called sardine fasting. So we get into all of that. We discuss Lots of different takeaways, different brands X, Y, or Z that Dom trusts. And I will leave the rest dumb. For God's sake, that's a long enough intro. So without further ado, maybe just a few words from the sponsors to make this possible. Please enjoy a very in depth conversation with the one and only Dr. Dominic Dagostino.

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14:18 Optimal minimal. At this altitude, I can run flat out for a half mile before my hands start shaking. And I'll answer your personal question. No seen. I'm a cybernetic organism, living tissue over metal endoskeleton. Me too.

14:37 Yeah. Dom. Nice to see you again. It's been a few years. Thanks for making the time. Yeah, it's great to see you, Tim.

14:48 Yeah, we've stayed in contact here and there with texting, but yeah. Lots of texts and Why not? This is one of the text threads I could probably actually make public in my life without some type of mutually assured destruction with many of my friends. I have been revisiting everything. ketogenic and certainly looking at exogenous ketones for a number of reasons.

15:10 And one of which We were chatting a little bit before recording is that I have a number of relatives who are deteriorating from neurodegenerative disease. including Alzheimer's. And one of them Is Apo E three three.

15:25 And my siblings and I are Apo E three four. Which would seem to indicate we would have Potentially. A Let's just call it two and a half X.

15:36 higher probability of developing something like Alzheimer's, even though Data might change. Who knows? Nonetheless, I'm looking to throw as much possible at this from a preventative perspective.

15:49 What data do we have? And if there's a little bit of speculation involved, I'm fine with that too, in terms of future directions of for research and what might come up. for applications of, say, the ketogenic diet and or exogenous ketones to something like Alzheimer's, whether it's From a preventative perspective, a mitigation of Or slowing of progression of symptoms or anything else.

16:13 Yeah, that's a a rapidly emerging area. Of research and I think you're aware we talked kind of previously of the case reports that are out there that kind of got put this on everybody's radar. I would say You know, they're early adopters of this idea.

16:29 were the people who understood that brain energy metabolism was pretty central. to Alzheimer's disease. Sometimes called type three diabetes, if you're getting that right. Mm-hmm. Yeah, that was coined back in two thousand five or six, I think.

16:45 And uh that was brought to my attention actually by Doctor Mary Newport and her husband. Steve Newport was The subject actually in the case report for the use of the beta hydroxybutyrate monoester. Or that and Dr. Richard Veach of the NIH was also on that. And Mary was near and dear to my heart. I actually coincidentally.

17:05 Hosting her for dinner. Last night at the house and had her over here and she's a a close friend of mine. We co teach together. at USF, she's a guest teacher. Interestingly, you know, I saw Steve Newport in two thousand eight or nine. I witnessed the observation He is a three four. He has Alzheimer's use three four for Apo, E four.

17:26 And He also had he had Lewy body dementia, but confirmed Alzheimer's disease too, uh when they looked at the brain. I was questioning this idea of Ketones rescuing the brain in the context of Alzheimer's disease. Symptomatically there was no doubt in my mind that it did because He wasn't using the Keto Nester at the time, but we

17:44 quickly transition to that after a meeting, but he was taking coconut oil and M C T oil. And he would bring these little shot glasses. Mary taught my class, we went out to dinner, he did the shot glasses His tremors stopped, he became animated, and he talked. And after about four hours he started to decline and started getting fine tremors again, and then he would become reanimated upon Increasing its ketones to about one to two. Which we'd give him like a thirty milliliter shot of M C T plus coconut oil.

18:12 That was mixed in there. So she was really and doing that three to four times a day with meals. So that was my you know first observation. And it was clear to me that there was at least a metabolic within the Alzheimer's spectrum. Alzheimer's is kind of a fuzzy Diagnosis. Sure.

18:31 Very fuzzy. I'd just kinda like to call it, you know, dementia, cognitive dementia. There's vascular dementia and there's A beta and tau and my wife was working on tau at the Alzheimer Center when we met. She was working under a guy who studied tau. Then there was people at their who studied amyloid beta and there was like the Taoists and the Beda and there was kind of like argument as to what was More profound, but a universal feature of Alzheimer's is amyloid plaque accumulation, but also now

19:01 We know that glucose hypo metabolism is central. to that. And as we age our ability to use glucose as an energy source decreases over time due to they thought maybe vascular reasons, but Come to find out it's a constellation of things, including the glucose transporter, the glute three is on neurons. Chyruvate dehydrogenase complex, which is like really the governor or the rate limiter of glucose metabolism in neurons.

19:28 That's PDH, pyruvate the hydrogenase complex in If you look at that protein for that, that decreases over time. as does the sort of catalytic activity of that enzyme over time. So we know that And then there's neuroinflammation, there's a vascular component. So all these things kind of contribute to metabolic dysregulation, but also a big driver is neuro inflammation.

19:52 And I do believe, as does Dr. Mary Newport, who is the author of that paper kind of with a case report and a number of other leaders in the field, including I'm blanking on his name, the chair of neurology at Harvard just gave an NIH seminar. on infection as an etiological agent for Alzheimer's disease. So Epstein Bar virus, cytomegalovirus, herpes simplex virus.

20:17 HP V, you know, can contribute to things like So we're probably talking about if w I mean Fifty, sixty percent of the population. having one of these things. Sure. Yeah. Well Steve Newport, the subject in that case report had bouts of herpes uh HSV around the eyes and and got hit pretty hard with that, but also people who have shingles I think they're at risk too. We know like Epstein Bar virus, you're

20:44 four or five times more risk for things like MS. You know, it's triggering the immune system. So I think there's a renewed interest in looking at Alzheimer's disease, you know, looking at the root cause. And I think metabolism is central. But the metabolic hit that may be contributing to dysregulated metabolism and neuroinflammation could be an infection, and I think there's accumulating evidence for that. I was skeptical ten years ago, probably when we talked However, this cat

21:13 putting on my radar and then I was in a NIH sponsored workshop on this, you know, looking at various aspects and The data presented by a number of different labs was very compelling. for this. So what does that mean? Our immune system is

21:29 There's the four horsemen, right, that our friend Dr. Peter Tia talks about. I think the fifth horseman is really the immune system. I like to add the six horsemen as our physical form, our skeletal structure. our bones, you know, and that that will give over time too. But the immune system is really central to longevity and the metabolic control.

21:50 of epigenetic regulation and metabolic control of immune system function is of very high interest. I know the Buck Institute has kind of refocused on that. And many longevity clinics are now Looking at that. What is your preferred device for measuring ketones these days?

22:06 For publications we've used the Abbott Version Extra because historically We've used that. However, when I recommend A meter to people, I generally recommend the Keto Mojo device because that has Kito Mojo. The glucose ketone index and so the glucose ketone index is the millimolar concentration of glucose over ketones. And the strips are about nowadays still less. I was gonna say, I don't know, a few years ago, they're about half the price.

22:35 And we've tested the Keto Mojo. So we have a human clinical trial where we did Breath, we did urine and we did precision extra and kitemo. All together and then subjects go into the chamber and We did metabolomics and everything else. The Kito Mojistently

22:51 gives us numbers that are more in line with our biological assays that we run in the lab, like the aliases on that. Yeah. Well let me just tell you what I'm up to. And you can tell me how ridiculous I am and off base or fact check as needed. Can you remind me of how to pronounce this? Dr. Thomas is it safe read? Am I getting that right? Yeah, he's a good friend and colleague. Doc uh Tom Seyfried. Yeah. Tom Seyfried. All right.

23:17 So In terms of Fasting. We've talked quite a bit about fasting. It still is very interesting to me and I'm Wondering just in brief. If you could

23:29 Without getting too too much in the weeds, but I'm wondering what the ketogenic diet does that Exogenous ketones. Do not achieve. And then I'm wondering what fasting does.

23:40 That the ketogenic diet does not do. But the way I want to get to that. Is to ask you Because for a long time I was doing a one week We could call it a water only fast, but let's call it a calorie free fast, black coffee and black tea and stuff I was consuming, but a week long water long fast a year and I was doing maybe a three day fast every quarter. I couldn't quite didn't really want to do like three to four week long fasts a year.

24:05 Just didn't want to do it. But in terms of potentially Purging precancerous cells and so on. I was like, you know what? I like the aesthetic practice. Seems like a bit of autophagy and cellular cleanup is a good thing.

24:18 Why don't I do that? Do you do any fasting anymore? Or is that something that you have omitted from The current version of Dumb schedule. Yeah, I do it situationally and I think There's situations where

24:32 I think I'll benefit from fasting or from just inducing a state of an energy deficit, right? So you could do Caloric restriction, time restricted. feeding, dietary restriction, uh you could do a restricted ketogenic diet. Cicly ketogenic diet, modified supplemented ketogenic diet, I guess, which is what I do. I like to do what I call I mean kinda

24:54 coined it it's like sardine fasting. And I had a cancer patient a long time. One of the first that I sort of engaged with actually you might his name was Dr. Fred Hatfield. So he was like kind of a famous Doctor Squat? Yeah, yeah, Doctor Squat. Back in the day. Wow. Yeah. We were good friends. He was a mentor to me in many ways, but He had advanced metastatic

25:15 prostate cancer and it went to the bones where they did like a pet And I was just getting into this area of research, and I was like, Here's what I would do. And I would go to his house and I'd bring him things and he was testing things and He loved sardines, so he kinda I think he steered me onto sardines in like maybe two thousand seven or eight or something like that. That was my love for stardings kind of was probably from him. But he would do

25:38 Low carb, he called it ketogenic, but I think it was just more of a low carb diet. And then he would do five days, he would do a fasting mimicking diet. That Valter Longo has advanced, but he has more of a plant based approach, but Doctor Hatfield would do, Fred would do like one or two cans of sardines, like maybe one can of sardine per day for a week. So we called it like sardine fasting. And that was Just as I was getting into this and Essentially what happened is that he went into rapid remission and the doctors didn't really know

26:08 Fred ended up passing away maybe Eight years later of something completely unrelated to his cancer. As a a non oncologist, I have to pause and just say, I mean, it seems like Prostate for a lot of people, they hear that, they think death sentence, metastasized prostate cancer. They think, No way, you're done. Am I Exaggerating? I mean how

26:28 frequent is it that people have complete remission of something like that. Maybe I'm Exaggerating things. Yeah, there's a lot of factors like the Gleeson score and his was, you know, not good and and a number of factors. So he was given I think he told me like three months to live. I mean, but he went years and years after that and he was like no evidence of disease. Uh

26:49 How often was he doing the Sardian fasting? Was that once? So every month. What did his cadence look like? He stayed ketogenic and then I would go over there and encourage him to do that. And he loved to do it. He was like, Okay, I do this and now I feel better like when I'm doing. Fred also, surprisingly, would smoke a little bit, and I got him to maybe stop that we

27:11 Got him to dial back on some other behaviors and maybe you drink a little bit too, but not that much, but His health improved dramatically when he adopted a low carb and then ketogenic diet. And then for years he did the sardine fasting and We communicated and I just encourage Hey, keep sending me your medical reports and maybe there is something to this. So that actually steered me into We did started Alzheimer's research because of Dr. Mary Newport. I studied Seizures because of

27:38 Mike Dancer. Just Google Mike Dancer Epilepsy and you'll find some remarkable stories. I kinda steered them to the ketogenic diet and it And it was a remarkable you got off all meds and it worked way better than the meds. But that was prostate cancer, but then I started engaging with other patients and then connected with Thomas Seyfried.

27:57 How frequently was Fred doing the week long sardine fasts, if you had to guess. Once a month. Sorry, yeah, I meant to yeah, it's analogous to the fasting mimicking diet. I think Valter Longo can do that, you know, he advises patients based on situationally their situation, but I encourage Fred to do it every month and his feedback to me was that he would do it once every

28:20 month to two months. He enjoyed doing it, so it was something that he kind of Like look forward to doing Sardine fast. I can't wait for that to become a thing. That's gonna spread. Yeah. I don't want to gloss over what you personally do. So for you, for instance, I found out recently and Everybody get your checkups, right? Do not skip colonoscopies. Do not skip in my case, I got an endoscopy.

28:44 because I was having some trouble swallowing every once in a while. I thought it was like, ah, maybe it's just like I'm eating too quickly with dried chicken or something. And suffice to say, putting that aside, that was sort of the symptom that catalyzed It but I end up having very unexpectedly A hiedal hernia. Hiatal, I think also related to the word hiatus. etymologically, but basically I'm gonna get the definition wrong, I'm sure. But

29:07 Basically From your esophagus to your stomach, typically there's a nice Kind of sphincter ring and basically The stomach is kind of pushed out of that ring and there's actually a lot of scarring in my throat.

29:21 From acid. So I was told that, you know, maybe not this bluntly, but that that puts me at some increased risk of throat cancer or esophageal cancer, some type of cancer. And I was like, shit, that's not typically what kill people in my family. Usually it's the cardiac stuff. And I feel like I have that. My lipid profile is very well under control. And Which is why going back and doing research for this conversation and I've also done fasting over the years.

29:47 I've thought, okay, well, in addition to taking the proton pump inhibitors and everything so that I'm not Accumulating more scarring. Yeah, is there a place? for doing the fasting since I don't mind doing it anyway, just to further hopefully decrease the risk.

30:03 And you were saying you fast Episodically, was that the word that you used? Situationally episodically. Situationally situationally. What does that mean? If My wife is traveling and I, you know, it prevents me from being anti social and I have a lot of work to do.

30:20 And I have the I have a grant deadline. It's five days away. Okay. I'm starting fasting for five days until I get this grant submitted. If I'm traveling by myself. I'll do it if I get for any reason occasionally, you know, I'll get like sort of An inflammatory flare up and I don't know what it's I'll feel a little bit off, like brain fog or my joints or something like that. It's pretty rare now'cause my

30:42 H S C R P is like non detectable, right? Before I did k it was always like one or two. So on a higher carb diet. Yeah, so people might recognize CRP, right? I mean uh C reactive protein is a marker of inflammation. I mean if you get Your annual blood test or whatever, chances are it's on there somewhere. Yeah, I'd like to draw attention to that real quick because HSCRP is a better indicator of cardiovascular disease than LDL cholesterol.

31:10 Like we know that now. Like if you s someone said that like ten years ago, they're just like, You think you're crazy. But yeah, HSCRP is what we call a cardiometabolic biomarker, including, you know, triglycerides and insulin and things that should be included. But that is a really important biomarker, I think, to keep low. For Alzheimer's and for cancer and All the other I call six horsemen now.

31:32 So things that I mentioned. Yeah, so occasionally I'll use it situationally just if I feel in my body if I feel like something is coming on. Like I'm getting a flu, but The sardine fasting is And I I advise it for cancer patients

31:47 I want them to avoid A water only fast in the context to prevent cancer caquexia. Yeah. muscle loss or muscle wasting. Yeah. And omega three fatty acids are very potent mitigators of cancer cachexia. So you have the omega threes and basically you have everything your body needs, especially like nutrition wise.

32:07 in sardines, you might want to add a little bit of vitamin C or magnesium or something, but essentially it's like you have adequate nutrition and then you have you create a caloric deficit. You create caloric restriction and then with caloric restriction come a whole host of beneficial things. The protein's low enough that you're suppressing insulin, mTOR, and probably activating AMP kinase. And if you do that in a protracted way and you can achieve a glucose ketone index of one to two for about three to five days. the constellation of things that if you measure that would sort of correlate with inducing and maximizing autophagy. So that was sort of the rationale for me to do that. And a lot of people talk about autophagy and it's kind of a nebulous term.

32:51 We measure it. We look at the autophagosome. So we're like a lab that actually does kind of look at Things like that. And there's like P sixty two and other things that you can measure, but There's no commercially available. I think the best

33:03 Way to measure the Suggest your in autophagy is a glucose ketone index. Yeah. Which Kyoto Mojo will do automatically. It'll do the calculation for you. I did have a quick question. When I compared

33:16 my keto mojo to a oral glucose tolerance test, where I was having Blood drawn every thirty minutes. The glucose readings I got from the Keto Mojro were substantially higher. Then the blood test.

33:32 the blood draw itself. And I was wondering if that's something you've observed. I mean, who knows? Maybe it's a bad device. Maybe I had too much alcohol still on the finger and I didn't dry it properly. I mean Who the hell knows, but Maybe it doesn't matter so much, but uh it seems to matter, right? Because uh regular spikes above a certain kind of nanogram per deciliter.

33:52 seem to be indicative of all sorts of things. Have you run into any issues with the device or any caveats related to specifically the glucometer side? What I do like What's nice about it is it does give you that glucose ketone index, the GKI As a read out. Right there on the device.

34:08 Or in the app at least that accompanies the device. Are you talking about measuring glucose at the exact same time point that a phlebotomist pulled blood? That's exactly what I'm talking about. Okay. And what was the difference between what Was measured that let's say the peak at

34:25 thirty minutes out after drinking this not so delicious, dexterous water. It's something like this. Like I was bumped up to probably one forty on the phlebotomist drawn blood, and it was like one sixty five on the Kito Mojo. And the return was much faster and much better on the phlebotomus drawn blood than it was on the Kito Mojo device, which is not to throw them under the bus because it could be operator error or just a single bad device.

34:54 And I have friends who have used it very successfully on the ketogenic diet, which is why I ended up buying it, because precision extra is kind of a pain in the ass to get a hold of at least On Amazon. So That was my experience and I was like, Okay. Well.

35:08 Tricky. Tricky tricky.'Cause I You know, if I'm if I'm really trying not to pop above a certain level. If the device I'm using day to day is twenty points above Where maybe it should be, then that's a problem.

35:21 What's your hemoglobin A one C? I'd have to go back and look. It's trending down. But I would have to go back and look. If you wear a CGM, you're under maybe a hundred, like with a CGM. So the meters tend to trend a little bit high, like about ten percent high. The Kito mojo was ten percent higher than our assays and the Precision extra was twenty percent higher than our

35:46 The assays. That we that we do when we pull blood from the animal. So if that helps. You want to look at your insulin levels, your hemoglobin A one C, H. Yeah, we we we we got it all. And just for people public service announcement. Do an oral glucose tolerance test. Ask your doctor, talk to them, get your insulin measured because my relative's metabolic dysfunction. was

36:09 Missed for a very long time. in part because they were looking at fast and glucose. And you can get really lucky with fasting glucose depending on when you get that snapshot. And I mean the docs weren't great to begin with who were tracking these relatives. But uh as soon as we looked at OGTT, the oral glucose tolerance test and insulin, oh my God, it was like Sky high out of range. Yeah, or put a CGM on them. That's what motivated me to be I guess, you know, one of the first advisors for levels and I've worked with them on a research front.

36:40 I think you've interviewed Sam. Right. Yeah, Sam. I mean, that's like the ultimate kind of, you know, metabolic optimization. platform. I mean there's others too, but simply wearing I mean now they have the Stella Stella device that came out, so CGMs are over the counter.

37:00 Now but the analytics from that and also the biomarkers that if you're part of that program that you can measure, which include, you know, many things that we could talk about. But that would capture your relatives if your relatives put a CGM on. You know, that's Really important. But What you observed is pretty normal and I not to probably be of concern.

37:21 Okay, cool. Yeah, I just wanted to check it out. Just a quick thanks to one of our sponsors and we'll be right back to the show. Many of you know how deeply I love Japan and its culture of unwavering dedication to craft, refinement, commitment to continuous improvement. But why do I bring this all up? Well the same focus.

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38:35 Tim. If someone uses just to tie this up for me and I maybe just missed it. If someone is using exogenous ketones on a continual basis, are there longer term adaptations? And part of the reason I'm asking.

38:51 Is that In the most recent s kind of set of experiments, let's just say I was strict keto for three weeks. And then frankly just got bored. to death of the diet. It's hard. So I did like Yeah. I did three weeks of let's just call it kind of textbook.

39:06 Protein also quite low, like ten to fifteen percent, let's say. So maybe I bump it up next time. But just got so bored of it after three weeks, but I want to do enough that there might be some upgrade of the metabolic machinery and we could talk about that, because I know for athletes it might be like six months to twelve months. But went from that to then sixteen eight intermittent fasting. Still in ketosis.

39:30 For maybe a week. So sixteen hours off, eating between let's say two PM and ten PM. And then I went to a more Paleo ish diet, let's just call it. Within that feeding window.

39:43 And I'd say did that for a few weeks and then started layering in exogenous ketones. in my fasting state typically eleven AM, one PM if I'm doing podcast recordings and things like that. And

39:59 Part of what I'm trying to figure out is Given um Ape OE three four. Scared to death of Alzheimer's. And maybe there's nothing to be done about it, but if there is something to be done, in addition to exercise rights and s kicking out the cloth, though and BD and F and all that good stuff.

40:16 From a dietary perspective Trying to figure out like okay, how long does Keto memory last. If there is a Expiration date?

40:25 And If you were in my shoes, how you would think about Not just the exogenous ketones, but fasting and ketogenic diet. Do you have any any thoughts on that?

40:38 Well yeah, you're you're d doing a lot of stuff there. And I would recommend following a protocol that you could do kind of day in and day out that should ideally almost be effortless and kind of mesh With your schedule, which may be variable if you have podcasts and things like that. But I also I'm of the opinion that, you know, you could follow like a baseline diet, which is A low carb Mediterranean like diet. Mediterranean's kind of a fuzzy term, I hate it, but Low carb Mediterranean style diet that essentially keeps biomarkers in check and then situationally going

41:12 Dicetosis now and then. To just Optimise it. You want to Follow inter

41:18 approach therapeutically that keeps your GKI into that one to four range. Tom Seaford is very adamant about one to two. But the normal GKI of a Person in the US is like fifty, right? Twenty five to fifty. So just

41:33 Living in a state of having a GKI of even five would be I think trending towards being more metabolically flexible, having greater fat oxidation, and then you want to As it sounds like you're doing just keeping check of your metabolic biomarker. So comprehensive metabolic panel, CBC, of course, if you're using. You know, different agents on that. But insulin, HSCRP, hemoglobin A one C, triglycerides, Apo B, you want to measure to LP little A, it's good to know. So unfortunately

42:07 Thirty percent of people. And this is probably important when navigating what protocol to use. I have a mutation. I did GB Health Watch. Which looked at my genetics for dyslipidemia. So GB Health Watch, Dr. Spencer Nadolski reached out to me because he was I was posting my numbers online and he was like, Hey, you need to do this test. So he's a very smart

42:28 aggressive er Proactive. Kind of Yeah, and suggested this Tess. He's like, I think you're a hyperabsorber. And it's like isn't like one percent of the population a hyperabsorber? But come to find out, about thirty percent of the population hyperabsorb cholesterol.

42:44 That's me too. I'm in the same boat. Okay. I have an MPC one L one receptor mutation that's a gain of function mutation. So I use a Zetamide monotherapy. For that. So a Zetamide, it was sold as Zetia, and I can get by with half of a tablet, which is five milligrams, and it half my Apo B. It put my Apo B They cut it in half and also half my LDL. So I can follow a ketogenic diet.

43:08 And I had the skyrocketing LDL Ape O B, but then I put that back in check. I am of the opinion that I need more data to come out. There's a group of people that think, you know, LDL in the context of optimal metabolic biomarkers that it's uh not to be concerned about, but that data is emerging and there's groups of people that I believe are credible and then working on that front, looking at the lipid energy model. With the lipid energy model, LDL and APOB is sort of a carrier for fat to peripheral tissues, but we don't have to go there. Yeah. Let's dodge it for now. Yeah, yeah.

43:42 If your LDL pops up, then a pescatarian Mediterranean like diet that's low carb. that ideally under a hundred grams of Carbohydrates per day. That's no sugar, no starch.

43:57 fibrous vegetables and fruits. So my rule of thumb is twenty five percent of what Carbohydrate you consume should be fiber. And then that'll essentially kind of make it non glycemic. What percentage did you say? So what I do personally is about fifty to a hundred grams of carbs a day and ensuring that

44:14 the carbohydrates that you're consuming, about twenty five percent of that carbohydrate is Fiber. So for example. Broccoli. You know, asparagus, of course, cauliflower, green leafy vegetables, but even fruits, like I trend towards Wild blackberries, raspberries, blueberries, and buy them like in combination. And then wild blueberries are about half the size and they have more fiber, less sugar.

44:37 So I have like a cup of that per day. That's probably my carbs come from Mostly broccoli. Wildberries. Dark chocolate and maybe a few other Where do you get wild berries?

44:50 Is that something you can buy or do you have to go out and f steal from your neighbor's patch? Surprisingly, blueberries grow great in Florida, but we have a blueberry farm right by us and they make it's a winery, so they make Yeah. Grow blueberries and then make blueber wines and

45:05 Things like that and have huge festivals. But we get from there, but Yeah, you can go to Walmart and get, you know, the Walmart blueberries, which are like the size of grapes, and then next to that now Costco. And Sam's and and even Walmart now have the wild blueberries. Oh, no kidding. Okay.

45:22 C Just because you mentioned LDL. I might be hallucinating this, so please correct me if I am, but Didn't you at one point dramatically cut down your L DL

45:33 Labs. By swapping dairy out, I think maybe heavy cream and using coconut cream or something else in its place. Or am I making that up? I took out heavy cream but put sour cream back in, but maybe about half. of the sour cream, but also just switched out.

45:49 The eggs. I think the eggs were getting to me,'cause eggs have a lot of cholesterol and I was eating like a dozen a day, so When I prepare my food in the morning, my dogs get my food. So I I'll make ten eggs, but I will do I'll have like three yolks and then I divide the other yolks between my two dogs. And then I also instead of like ground meat, which I was eating a lot of, I get chub mackerel. I do sardines, occasionally tuna fish, but I get Cases of uh chub Chub like the insurance company? C H U B. No. How do you spell that? Yeah, uh C H U B. So a chub ma unlike a king mackerel, which are bigger, chub mackerel are small fish and they Yeah, they don't bioaccumulate as much garbage. Yeah, so they're Really low on the sp

46:34 On the um the heavy metal list, which I I tend to check because I eat so much of it. So one can is almost a pound and there's three fish in each. I take a fish and give my two dogs each a fish. Then I pour it's got a lot of Fatty water in it. of omega threes and I pour that on their food. And they love it.

46:51 Where do I sign up to be reincarnated as one of your dogs? Yeah, yeah. Yeah, they get yeah, this morning they got my wife Audacious has an audacious canine supplement. So we give them and that's got spirulina, ketones, and a few other things. We give'em that creatine monohydrate. Hold on, I can't skip over that. Why give ketones to your dogs? Well The brain boosting effects, the anti inflammatory effects, the neuroprotective effects, and the anti cancer effects. So these are all things I worry about with my dogs. They are fixed. I do give them a SARM.

47:23 This is an anabolic, right? I do, yeah. I transitioned. They got attacked by a big pit bull and they, you know, kinda immobilized for a while. So it was like I was gonna use it for a cancer cachexia study. And it's osterine, I think. So I yeah, started giving it to them and it seems like yeah, they are leaner, stronger. We have a great dane that's twelve years old that makes them like ninety to a hundred human years, and he runs thirty five miles per hour. Like he has like no sign of slowing down. Yeah, he's like He's a great dame that should have passed away years ago and he's just like a machine. You mentioned audacious nutrition just for the purposes of

47:59 Transparency. You do have family in the business involved with Audacious, right? Just to confirm. Yeah. I can't have any company. I don't sell anything personally, but yeah. My wife decided to create a product that sort of use the ketones that we actually used in research. So evolved out of that was various salts and the idea was that if that product was created, then we can use it for research.

48:22 And that was the initial part. And that's kind of what I I was using it anyway. I was like, Well, why don't you just make a product out of this? I can't do it. But it actually was a an I Corps NSF program. through the university that got that Started. Question. Do you give Wrap a mice into your dogs, or would you?

48:39 Or to yourself, do you currently or Take or give your dogs rapamycin. I've went back and forth. I follow Matt Camerlin's work, you know, pretty closely and go back and forth and I've decided not to just Because of the immune suppression. And I got about a handful of

48:57 people that use it and I would say half of them get sores in the mouth. Yeah. That's super common, the mouth source. Yeah, the data's too early for that. And I think the same thing can be achieved. A bigger lever would be sardine fasting for one thing. And uh just beta hydroxybuter H.

49:16 You know, and a well formulated, low carb Supplemented. ketogenic diet, by definition, a diet that elevates ketones. And exercise, right? So exercise and a whole host of other lifestyle things. I'm not ready to pull the wrap of mice and Trigger.

49:31 Anything I do with my dogs, excluding the SARM, I haven't used that, but seeing the effects and looking at their blood work, it looks perfect. So There are no no side effects with that and it seems to be helping Can you take just a paragraph explain w what this Sarm refers to for people. Yeah, there's a specific androgen receptor modulator that is sort of hits the androgen receptor, but doesn't

49:57 have the androgenic Like Qualities. It's not gonna give you a third Adam's apple, but but it'll help with muscle growth. It helps to stimulate

50:09 Skeletal muscle protein synthesis in the context of this drug also bone metabolism. And both of our male dogs are fixed too. So We have a discussions with various vets that are of the opinion they're more progressive that your dog should be on like TRT if they're fixed because that'll increase the quality of their life, especially as they age. I can't detect any loss of skeletal muscle mass, even when I look at pictures. And for for clarity, your dogs are all male? Yeah, we have two male dogs and both of them are considered advanced age and the the black lab is showing it a little bit. He has hardware and has two back legs. We had two knees put in with him, but he was a little bit heavier and now we've dropped his weight.

50:53 With what why feed him now, which is essentially Fish, meat, eggs. ketones and we give them a mushroom supplement that's a lion's mane and a a rishi maybe cordiceps and a few other things. And then I give them creatine, monohydrate. So they get yeah, they're pretty optimized as as dogs. And I think the the big thing is that we live on a farm and they get a lot of activity too. They get two non negotiable walks every day. And that's I do that for for me too. That's part of like my creative downtime is to do a non negotiable walk like morning and night. So

51:27 Uh and they get a lot of that and they chase our animals around too. So what are your current feelings on let's just say on the Sardine Fest? when you're doing a week long sardine fast. And maybe you're so adapted at this point that you don't experience this, but Certainly when I've done water fasts and even if I'm doing Lower calorie. ketogenic following a lower calorie ketogenic diet.

51:48 I can have a really tough time sleeping. At least for A handful of days. have just kinda rapid heart rate. I don't know if that's trying to compensate for lower blood pressure because I'm Just losing so much water and electrolytes, who knows?

52:01 I have found supplemental electrolytes to help a bit. With that. But What type of supplementation Do you take or advise people take? if they are trying a ketogenic diet for the first time or fasting. Maybe the answers are different.

52:16 Let's just say it's a sardine fast, like a Man. Falter long. Coming for you with the sardine fast. So the what supplementation makes this Easier or

52:30 more productive. Just from an adaptation perspective. I will use sardines and also ketostart, which is essentially, you know, the electric sodium, potassium, calcium, magnesium, beta hydroxybutyrate, and that will be used like two to three times per day. At night time, yeah, when you go With a caloric deficit, your sympathetic nervous system is activated a little bit, especially with a water only fast. So you get a little bit hyper or

52:57 Dysphoric even for some people. Yeah, feel like you just ran up Three flights of stairs when you're trying to go to sleep. Yeah, it's unpleasant. Yeah. So that's less with a sardine fasting instead of like zero calories. So the sardines would then be eaten at nighttime typically. I remember doing this repeatedly and what I would do is take a little bit of GABA at night, and on one or two fasts I took just twenty five milligrams of diphenhydramine.

53:25 I think that's exact or close to the exact dose of One or two Benitry, right? I'd have to look at it. But isn't diphenhydramine. Yeah, diphenhydramine is uh histamine It tends to be lipophilic, which means when you take diphenhydramine, uh, it quickly crosses the blood brain barrier. You can be a little bit groggy the next morning. The studies show that fifty milligrams of diphenhydramine can decrease, you know, memory recall if taken acutely, but twenty five milligrams, there's no effect of that. So I'm comfortable with taking twenty five milligrams of diphenhydrame at night and then giving a lecture the next day in the morning. I feel raised are sharp and because also

54:02 It reduces sleep latency, so I get better sleep. I would not use it more than like once a month or something. And I do think diphenhydramine and these over the counter sleep aids used every night by various people that are emailing me, I mean, is creating dementia. I think. Yeah. I think the data's pretty clear on that. You have an older person getting fifty milligrams every night, every week is bad. So melatonin, magnesium. A small dose, I guess for my size it would be a half dose of diphenhydramine, and then GABA.

54:31 So you could take GABA in the form of GABA that you can get over the counter, or there's also Fenny But Gab, so which I have but tend to haven't used in a while. Fanny but I just want to put out there can be a really nasty drug for people. It could be addictive, you build a tolerance real fast, and coming off of Fenny Butte can be very problematic for people. I mean it's like coming off their G H B, I think. But it could be a tool in the toolbox because I mean we're talking about taking like two, three grams of FentyBut can give you euphoria.

55:01 And you have it's like a benzodiazepine kind of, but if you take two hundred and fifty milligrams or two hundred milligrams of Finibu, which is a small dose I mean theoretically you could take that two or three times per week and never really build a tolerance or get, but I would not advise people to do that. But if you're going to fast, like say once a month one way to avert that and I get the same exact thing, I get super hyper and my brain just goes on fire when I do the first day of fasting.

55:27 Yeah, a little bit of GABA. Orphanibute, diphanhydramine, magnesium. I've always done melatonin. Five to ten milligrams of melatonin. Oh, that's a solid dose. Yeah. We went on vacation and I forgot it. Do you still use melatonin continually? Because I remember there was some conversation floating around the ether and never look too closely into it because I don't use melatonin all the time about some possibility of endocrine disruption. Yeah, I've been using melatonin.

55:56 Probably when I started using creatine in nineteen ninety. Three. The old phosphogen when I was in high school. Oh man, back in the day. Yeah, yeah. EAS is that I was a beta tester for that. Yeah, I was a beta tester and then phosphogen came out in nineteen ninety three, I think. I started using creatine. I was like a early adopter. I'm creating.

56:14 But yeah, to get to your question in melatonin, I've studied melatonin on the hippocampus on brain slices. You can slice the brain like a piece of bread and a applied melatonin looked at you know, reactive oxygen species and things like that. We use it for oxygen toxicity. It wasn't good for that because it did make the rats sleepy. Melatonin doesn't really make me sleepy. It kind of makes me more calm.

56:36 Than anything else. So I went on a vacation where I forgot melatonin and I slept like a baby, probably because I was up every morning, you know, sun is the ultimate circadian synchronizer. So I got off of melatonin to check my endogenous melatonin and there was no suppression. Melatonin in animals that are hibernating, like little gerbils and things like that, if you give them melatonin. It can suppress endocrine function, including testosterone production.

57:02 Huberman talked about I love Huberman. So I was following him and he was talking about melatonin. And so I went to the primary literature and I was like, man, he's right. It is an endocrin disruptor and suppressor. But then I dug into the literature more and it was not the case for humans. So there was no evidence in hum and I think when he talks about it, I don't think he references like a human study, but he does reference legit studies and uh Andrew Huberman is an amazing scientist and he puts out awesome information out there.

57:27 But it did get me concerned about it, so I got off of melatonin and then I confirmed that my body does make normal amounts of melatonin. So I measure that. I also confirm that five milligrams of melatonin If I go and measure the next day. My melatonin is off the charts, meaning that I take five milligrams at night.

57:47 The next day in the morning at nine o'clock or ten o'clock in the morning, my melatonin is like super physiological. Is that good or bad? I think it's good. So I take melatonin not to sleep, but as a neuroprotective agent that has a whole host of beneficial effects for the brain. Also Alzheimer's disease also Cancer, especially breast cancer. So use it.

58:10 For that I also mega dosed twenty or thirty Milligrams and then checked my L H and F S H. Milligrams? Yeah. Okay. Yeah. Yeah. So twenty to thirty milligrams. Ten milligram tablets are like the gorilla tablets for melatonin, right? So I I chew a bunch of them and then held it under my tongue. And I didn't really feel any more sleepy. I just slept like normal. You know, my aura ring was like normal. But then I went and I got lab work done.

58:36 And I did testosterone, LH, FSH, and there was no suppression. Actually, my LH and FSH were trending like high end of normal. Which is another topic that I get into, but The thing is that it did not trigger An endocrine response in me. I do not think there's any data in humans, although specific animals are very sensitive to melatonin. And if you give it to them, it can cause endocrine suppression of some sex hormones.

59:03 So it is a hormone. Well that's good to know.'Cause I actually Benefit from taking melatonin. But I Largely.

59:10 Cut it out because of some of the the murmurs, but I do it does help me sleep. Is this a true statement that you do not do any Fasting. currently, or like pure water fasting.

59:23 But instead do This situational Sardine fasting. And I mean, is that sort of ninety nine percent of the

59:32 Bang for the buck, and there isn't really any reason to go beyond Something like that as a fast mimicking diet, or are there benefits that you think are compelling of doing a more restrictive Say water only fast where you're allowed black coffee and a few other things, perhaps, but

59:48 or otherwise really not consuming calories. For me personally, it's very context dependent. I was talking to someone the other day that was getting shingles. As soon as the first sign of tingling, which is like the precursor of getting shingles, I start fasting and it never actually surfaces. So only when they situationally pull the trigger and start water only fasting does it completely mitigate. It's a massively effective countermeasure for RP simplex flares or things like that. Yeah, I was gonna ask I don't know anything about shingles. So what's happening there?

1:00:19 do like a endogenous Keetones and therefore could you just take a bunch of shots of exogenous ketones or like what's actually happening? to have that suppression. I think we're

1:00:31 Augmenting metabolic control of immune regulation in the context. So You have the innate immune system, which is always kind of running around and then work we're doing now with the Moffitt Cancer Center is basically using ketone metabolic therapy to augment the adaptive immune system. So the adaptive immune system is more specific. It's kind of like, you know, that B cell and T cell, like augmenting the B cell and T cell.

1:00:58 Things where it's like the adaptive immune system is like the Navy SEALs. And there was a human study that used a vegan diet versus a ketogenic diet. And this got put on my radar by numerous people who then wanted to research this. A vegan diet actually augments and enhances the innate immune system. And a two week ketogenic diet, and this was published in Nature medicine.

1:01:20 augmented the adaptive immune system. partly through the gut and partly just through changing metabolic physiology. This happens when we fast. If we're fasting Our gut is like relaxing. I think it's restoring or preventing, you know, when we eat something, we have things going into circulation that's keeping our immune system kind of active, right? So if we're not eating anything, our immune system becomes hyper vigilant.

1:01:45 And then in a way that it becomes hyper vigilant. to attack things, but at the same time it's suppressed. So inflammatory markers go down. The immune system is like an army. You have like a hundred thousand guys like in an army in the immune system and then they're

1:02:00 All working if you're eating and you're stressed and environmental toxins and things like that. When we fast, we allocate more of that immune system to be more vigilant to attack things, but at the same time, our general inflammation state goes down. it just becomes more vigilant, but inflammatory cytokines, chemokines kind of go down. So I think that's part of it in that it's stimulating

1:02:25 I think cancer specific immunity, but also just generally suppressing inflammation. And that's happening for a number of different reasons, in part due to elevating beta hydroxybutarate, which is An endogenous metabolite that plays a role in inflamazome Suppression. I know guys like maybe Eric Vernon and Like the guys at the Buck Institute kind of looking at that and then

1:02:48 Our colleagues Doctor Deep Dicks at Yale. I sort of formulated a diet to specifically elevate BHB because he had showed previously that fasting suppresses the N L R P3 inflammosome and the metabolite that's off the charts with beta hydroxybutyrate. So the next study was giving that as a supplement with a normal diet to see if that could then also suppress the inflammosome. And it did.

1:03:11 And that was published in Nature Medicine Two thousand fifteen. So I formulated the diet like for that study and I've become like a middle author on that. So I think that Plays a role. In that, but I think it's multifactorial and I think it's like it's just one of these things that needs to be studied because it's kind of universally accepted.

1:03:31 Yeah, it's kind of happening. But you also have to be in a good healthy state. If your nutritional status is low, it depends on kind of your baseline characteristics. Your therapeutic response to fasting. And I think that's really important, especially for people who have cancer, maybe getting chemotherapy where they have compromise nutritional state in some ways. They'd have to approach it very

1:03:52 Cautious. How many meals per day? Do Eat now. How old are you, Dom? Uh fifties? Yeah, fi I just turned fifty fifties, yeah.

1:04:01 All right. Well congrats. What does your diet look like? No. Just like a kind of The The set it and forget it version of

1:04:10 Dom's diet. What does that look like? It's situational, but always probably three meals per day. Yeah. And you weigh about how much at this point? I just did a DEXA this weekend, actually. I did a DEXA

1:04:20 Two weeks ago and I did another one after I got off creatine and then did another Another one. So I just hover it at two eighteen to two twenty. And body fat last was nine point four. You got some muscle to feed. All right. So three meals a day. What does it look like? Uh this morning it was eggs and chub mackerel and that's it. So basically it's just like protein.

1:04:42 And fat Mm. Lunch I typically have You know, beef, chicken or Fish, usually fish.

1:04:51 Lately I've been eating a David Bar. Peter sent me some of those and I've been I have kinda like mixed opinions about it. It pops up on the CGM a little bit, but I think it's kind of an Uh interesting. direction to go into. I enjoy them. They taste really good. Right. So uh been doing that and then For dinner.

1:05:07 We went out for Mexican The other night and last night hosted. Mary Newport. And usually you have like beef, chicken, or fish with A vegetable, like always broccoli. I'm a huge fan of broccoli. I could eat like three pounds of broccoli has no gas or bloating effect for me at all. So somehow my body is just My body loves broccoli, so I our dogs do too, so I give them

1:05:27 A little bit of that salads, but usually about a pound of beef, chicken, or fish at dinner. So that's my big meal. Over the years we have transition instead of eating at seven, we eat at like five. Five or five thirty. So we eat earlier and then I do physical activity after that. If it's squats or deadlifts, I have to do it before I eat, but for like pressing movements and activity I do after that and I do farm work for like an hour or two.

1:05:55 in the evening after that. And I typically have like Every other night like wine. So I'll have like I do have A bit of wine. Lower alcohol non sugar Dry farm wines, which has like less than one gram of sugar per

1:06:09 I would never drink wine. without doing like some kind of activity after like wine at nine o'clock and then try to go to bed. Like I would never do that because I see that on my aura. But if I do like a glass of wine and some form of physical activity, we always do an evening walk. I I think I sleep better. I think I don't do two glasses, but I just do One glass. I know the

1:06:28 current consensus on alcohol is that it's But I would push back because none of that is specifically studying wine. If you go to the studies on wine, it actually shows The first one that came up is actually decreasing cancer risk. And then I noticed that when I take wine and measure my blood It's less viscous, so wine also decreases platelet aggregation.

1:06:51 So the it makes your blood less viscous. So and that is well known. I observed it and it was like something's going on here. And then I went to PubMed and it's actually Well known. I didn't know it at the time that It decreases So less than potential for clothing for stroke and things like that. So I think

1:07:09 That may factor into we just got back from Greece. And they had the Uzo and everything. And just like all the we went to then we went to Sardinia. So we went to these Blue zones. And they just, you know, at night after their dinner, the males will do like a shot of alcohol. Usually wine, but sometimes uzo. And they're all like in their nineties and like a hundreds, right? They're in the blue zone, so

1:07:31 It's a universal characteristic. Well that that's probably the There may be a genetic component too. I remember there was this book that was like why French Women Don't Get Fat or something. And way back in the day, I remember before his passing, I was talking to Charles Polyquin. He's like, Yeah. M T H F R he's like that's why it's none of the other stuff in the book. And he mentioned a couple of other things, like who knows? But the um Yeah, I mean I I think Activity Yeah. Living by the water, activity and sh social. So the social interaction is probably the biggest lever. I mean, I just see them they're all out and about walking around and yeah, that's probably the biggest lever and getting sun.

1:08:10 So they're outside in the sun, everybody you know. It's multifactorial, but it doesn't seem to be hurting them. Let's put it that way. If someone is let's just say they want to test out the ketogenic diet, and certainly they will note they'll be like, wow, Dom doesn't eat a lot of vegetables except for a pound of broccoli at dinner. I can tolerate that, but I have like probably like It comes out to thirty to forty grams of fiber a day, which is pretty high, but that's Broccoli

1:08:36 And uh I usually have a small apple too. Sometimes we have apples and then a cup of wild blueberries. So it comes out to Oh right. Okay. Abo thirty grams. That's maybe a higher Sometimes ten or twenty, but I try to shoot for about thirty grams of fiber. Yeah, got it. Okay. If people want to kick start

1:08:53 The uh ketogenic diet. Any tips for kind of getting over the hump. In the beginning. People tend to so you can sometimes have a bit of a hard time before they kinda click over. I'm not sure. For me, it's like once I'm above one point two millimolars, I feel totally fine.

1:09:11 That's just me on a precision extra. But For people who are Looking to give it a shot and maybe haven't given it a shot. Any tips for novices? I would do

1:09:22 Fasted low intensity cardio for me that would just be going for a long walk. You know, waking up in the morning and if you're gonna start Your ketosis experiment or whatever you're doing that morning, getting out in the sun, staying well hydrated. You could take MCT and also ketone electrolytes, like ketostart or something like that, and then that will ease the transition because it takes a little while for your

1:09:46 ketogenesis to ramp up due to you gotta deplete liver glycogen and ramp up beta oxidation fat enzymes, and then you have as ketones get into circulation, Over the period of a couple of weeks you're going to upregate the ketolytic enzymes, which are basically the enzymes and the tissues that are able to, you know, utilize and leverage those ketones for energy over time. How long does that adaptation Take, would you say? You know, I don't know if anyone has unambiguously answered this question in humans, but in rodent models you could see

1:10:21 The MCT transporter, not to be confused with MCT oil, but the monocarboxylic acid transporter, and now there's one, two, three, and four. That protein is fifty percent higher after two weeks, like in a rat, for example. I think the point is for most people is that If you start fasting or ketogenic diet and to avert the keto flu, you want to hydrate, get in electrolytes, and also elevate ketones as much as possible. And to do that. with MCT if you can tolerate it, or ketone electrolytes. I would not be guzzling a ketone ester because you're gonna spike ketones up, you're gonna inhibit your own ketone production.

1:10:59 It's a dose dependent thing, but my advice would be low intensity cardio, hydrate, electrolytes, and then small Amounts of ketone electrolyte with M C T. So M T T will stimulate your own ketone production too.

1:11:14 Now are you just taking tablespoons of liquid MCT? Are you using a powder and mixing it in? What do you personally do? Or what would you recommend? For the liquid, sometimes what I do, like if I'm eating tuna fish, which is like packed in water, I'll pour the MCT on the tuna fish and stir it up and then deliver it that way. If I'm having coffee, I can put in the MCT powder. in the coffee and mix that up and that'd be, you know. Ten, twenty upwards of thirty grams. And

1:11:45 Work by Stephen Cunein actually showed that if you take M C T in the context of caffeine or coffee, you can boost your ketone production by like twenty or thirty percent. So There's a bit of a ketogenic synergy when you deliver caffeine with MCT, it's stimulating lipolysis and also fat oxidation in the liver. What type of powder do you like to use? People send me things, but I actually the powder that I have is actually it's Keto Brains. It's MCT powder, Alpha GPC. Theanine and

1:12:16 It has lion's mane, mushroom in it. It goes under the brand name of Keto Brains, and that's the MCT powder that I use. The base of it is MCT, but then it has sprinkled onto that. Theonine, which has a nice calming effect. Which probably good to use, like on the first day of fasting. Alpha GPC, if I take too much of it, it gives me a headache. So I only do like one or two I gotta be careful with alpha GPC. I also get a headache. Yeah. Oh really? Okay. So you're like the first one. I don't know if I was create, but yeah, I did, you know, when I first got keto brains, I did like six scoops and I was like, Oh my God, I got a had a bad headache. I love that your first go is six scoops. If I just wanted off the shelf.

1:12:57 M C T oil,'cause I just like I feel like there's there's only so many medicinal mushrooms that I can cram into my diet. also, but no no offense to the mushrooms, but actually have some interesting thought on some of them additional mushrooms. Some of them are very strongly antiviral and immunomodulatory. And so When I've talked to a number of

1:13:16 very credible mycologists are like, Yeah, it's probably best not to take that stuff every day. Like you should cycle on and off. But if I just wanted to M C T for purposes of travel, right? Because M C T liquid can create such a goddamn mess when you're traveling. And in your pants too, yeah. And in your pants too, yeah. And for people who are novices, do not do creatine.

1:13:37 Caffeine. And MCT oil out of the gate. You gotta prove to yourself that you can handle that. Unless you're unless you're gonna work depends on the airplane. Yeah. What other just MCT oil Powder's.

1:13:50 Might you recommend. Or have you used it? Quest M C T Powder. I think you can get that in like C VS and Walgreens now too. And Amazon, just the neutral cost. So I bought Just straight up MCT. They also have like a C eight powder, and I've tested both of them wearing a continuous ketone monitor.

1:14:09 Yeah, and it saw a nice elevation over time, and then I combined that MCT powder with Keto Start, and basically I was in ketosis for half the day. So just dosing twice a day with that. I mean, I'm gonna break my own rules here, but I've done enough test drives. I'm about to go to not super high altitude, but I'll be coming from sea level to about eight thousand feet on average. And we're gonna be doing a lot of intense exercise. So maybe my morning dose Of coffee.

1:14:37 Which I'm sure will be some shitty instant coffee, but it's gonna taste delicious when you've been freezing your balls off. All night. Maybe I'll add some keto start. And M C T powder to that,'cause those would be easy to travel with. I would imagine.

1:14:50 I'm not sure how. Keto start tastes in coffee. No, no, don't do that. No, they have keto spike coffee. So Audacious Nutrition has Keto Spike Cocoa. coffee and tea. So in the afternoon I don't do caffeine after twelve, so I will brew I'll just boil hot water and just put and the Keto spike coffee is like a good Colombian coffee and it just has, you know, the B H B electrolytes in it. So I've been doing that.

1:15:15 All right, cool. I'll check that. I'm just trying to figure out because I went back through all of our conversations, which covers a lot of technical, as you would imagine. And I'm just wondering what you are most excited about and

1:15:32 Right now I I I mean just to volunteer this, I'm very interested in Neuroinflammation. And the inflammosome. the interplay with the microbiome and how the microbiome can seemingly influence or mediate some of, for instance, the anti-seizure effects of the ketogenic diet, right? If you

1:15:51 Get rid of acromancia or a few other strains. Lo and behold, doesn't really work. And I'm wondering if that applies to other conditions that metabolic psychiatry might be applied for, like schizophrenia and others, I don't know. But seems interesting. Has a question.

1:16:07 What types of questions or Projects or Realizations. Findings, anything. have captured your interest or excitement these days.

1:16:16 Just quickly go down the list. Ketone metabolic therapy for cancer. So is one. And we have a pretty comprehensive review that describes the framework for ketone metabolic therapy. For glioblastoma, which is a cancer that's largely resistant to the standard of care, so way too much to talk about. It was actually like a two hundred plus page paper that was gonna be submitted and we had to like basically put a lot of data in things as supplementary figures. I think there's like six supplementary figures that tell specifically all the different metabolic drugs that target glucose, glutamine. GKI calculator and a lot of things. So yeah, just Google like ketone metabolic therapy framework for glioblastoma and it's open access.

1:16:59 So that has stimulated research at different places, but I'm excited about research that we're doing with a Moffitt Cancer Center, which is the largest cancer center. Or one of the largest in Florida, uh, tier one cancer center where we've got various projects, glioblastoma, maybe a breast cancer, but also lung cancer. was specifically using ketone metabolic therapy. to augment immune therapy, specifically the checkpoint inhibitors. And that has to do with what I described about ketone metabolic therapy, specifically beta hydroxybutyrate.

1:17:33 activating the adaptive immune system. and making checkpoint inhibitors, which is a class of drug that's and CAR T therapy. So now they ha actually have a study with CAR T therapy. and checkpoint inhibitors. So ketones tend to expand the T cells that are associated with CAR T therapy. So just kind of enhancing that therapy. And with the checkpoint inhibitors, it tends to just enhance cancer specific immunity. That is augmented by PD one inhibitors. So they're specifically studying that. So I'm I'm excited about that. So that's on the cancer front, and then we can jump.

1:18:10 If you have no questions, I could jump to other the Alzheimer's the metabolic psychiatry and Yeah, let's talk about those. Let's hop to the Alzheimer's and metabolic psychiatry. Would love to dive into that'cause that's front of mine. For me and

1:18:25 Just as a as I'm not sure if I made this clear. Doing the Couple weeks of strict ketosis. segueing to a sixteen eight ketogenic diet and then moving to kind of a paleo ish diet.

1:18:41 has produced some of the best labs. I've ever had and also the best oral glucose tolerance test. that I've ever Logged and from a mood stability standpoint, I am also, for at least the last few weeks, supplementing with The monoester?

1:18:58 And a diester. The sort of U I T O N E. But all of those things combined, I gotta say, psychologically, from the standpoint of sustained focus and mood, has been just Kind of mind blowing, to be honest. So I yeah, I'd love to hear

1:19:14 Any and all thoughts on Alzheimer's metabolic psychiatry front? So metabolic psychiatry, I would encourage people to listen to Chris Palmer? Who you I kinda put on your radar. I don't know if you remember I sent you the link to metabolic data. So it's like you've got to watch this, Tim. It's going to change sort of the landscape of psychiatry.

1:19:34 Yeah, I remember used that that was a recording from a conference, I believe, where he was interviewing one of his patients on stage. The Metabolic Health Summit. Yeah, the Metabolic Health Summit. So which is part of Metabolic Health Institute, which is you can get educational credits through that. So yeah, we brought Chris in and it was such a compelling story. He treated Matt Bazuki? So Matt Bazuki is the

1:19:58 Son of Jan and David Bazooka and they because he quickly remission who are well known from Roblox. Well known from Roblox, yeah. Sort of billionaire philanthropists that are changing sort of the actually what ultimately maybe the standard of care for psychiatry. And I think they kind of single handedly are funding metabolic psychiatries with Sabani Sethy, she's at Stanford.

1:20:27 Chris Palmer at Harvard. And I work with them closely as an advisor. There's at least a dozen other institutes that are doing metabolic psychiatry research for Schizophrenia, bipolar, major depression, anorexia nervosa, which is a psychiatric disorder that kills more people than any other disorder, and a range of different things and anxiety disorders and alcohol use disorders, alcohol withdrawal syndrome, so they're doing research on that. So with metabolic psychiatry, there's a lot of pilot studies. Mostly bipolar, looking at a range of different things, ADHD to

1:21:01 And then there's apps that are emerging like MetSci, MetSci.com. Uh that's a collaboration with Allie Houston, he's at Oxford, and Georgia Ede, who might be good to have on the show. She's from Harvard. psychiatrists, so That app is more of a comprehensive app that incorporates ketogenic therapy, but also lifestyle stuff. And then coaching. So metabolic therapy, coaching for mental health.

1:21:29 So how do you spell the name of the app? Metsi is M E T P S Y, right? M E T 'Cause they're better at the size than the branding. Yeah. Yeah. M E T P S Y dot com at size. So I think they have their website up. So they're basically like in their onboarding phase, so they should go live pretty soon.

1:21:52 But I'd like to add that the bazookies, I remembered that They are funding a big study at Oxford right now, and the bazookis will match dollar for dollar, like any donation and spearheading. sort of that using the app and using ketogenic therapies in combination with, you know, lifestyle therapies. Metabolic psychiatry is rapidly emerging. And this ties into work we did. I guess my wife did I was on the paper, but she ran the study.

1:22:18 We were doing seizure studies with exogenous ketones and the most efficace one for this application was the racemic ketone salts in the MCT. So we are gavaging them What does gavage mean? It's basically like tube feeding the animal. So instead of

1:22:35 Mixing the ketones in with the rat chow, they eat it. And so it's taking a syringe and based on the weight of the animal, you pull in the amount of ketone ester or this case it was M C T and ketone salts. We did the Esters too and it it did have An anxiolytic effect, anxiety reducing effect. And then you administer that to the animal and what we're doing is, you know

1:22:59 We do seizure studies, put them inside a hyperbaric chamber, and we go two to three times more normal and it induces a seizure. But what we observed when we put the animals in ketosis is that instead of them trying to bite us and kill us and not wanting to be held, they were very chill and calm. So It was just, well, this is great. We can handle the animals easier and get them into the chamber without them trying to bite us. And my wife's a behavioral neuroscientist and she was like, Well, we should do some behavioral studies because I think there's something here. So we did elevated plus maze. So in this

1:23:30 case the animals can go inside. a closed little cave or it can come out into the open arm. In the elevated plus maze, which is exploratory behavior, like they're more extroverted if they come out, and more introverted. and kind of like, you know, their fear response if they go into the cave. So we got results that we published. The title is like Enxiolytic Effect of Ketone Supplementation. You know, we published, I think, three papers and showed like the mechanisms and stuff too.

1:23:59 So that was an early paper in over like ten years ago just basically showing that inducing acute ketosis with this formulation and doing the elevated plus maze produces an effect that was analogous to a dose of benzodiazepine. Like if you look at like, you know I don't know, Xanax or other things and elevated plus maze, it was like yeah, twenty or thirty percent more time in the open arm. So they're less fearful to be in environment and making them More like a social lubricant, maybe like, you know, a benzo.

1:24:31 Or something. So it had that effect in the animals and when we look at the blood work and even the take out the hippocampus and the brain, the levels of GABA to glutamate are higher. And then in another study we did with Angelman syndrome, we looked at the mechanism of that. And there's an enzyme called glutamic acid decarboxylase. And a lot of anti seizure drugs kinda target that. So that The protein levels were higher.

1:24:54 Essentially showing that your brain converts more glutamate, which is anxiety evoking, like wakefulness. Enzyme, it's converting more glutamate, which is excitatory, to GABA, which is brain stabilizing, that's like your chill. You know, like alcohol. It's what you take before bed. Yeah. Yeah. Yeah. So that was, you know, in a variety of different studies. We also looked at adenosin receptor signaling. That's a little bit more complicated to describe, but there's a number of different effects to that.

1:25:24 So there's a clear rationale, I think For depression, if you do an FTG PET scan on someone that's depressed, it shows glucose hyper metabolism. One thing to mention, I think an important thing to mention in the context of bipolar you can have a hyperglycolytic effect. And Dr. Ian Campbell.

1:25:42 From Edinburgh University has published some elegant reviews and is doing some work on that front and sort of describing the research there, but I think it's important because some of the feedback coming out, and I think you even mentioned too, when ketones get really high. What we observe if ketones get too high, that can cause an anxiogenic effect.

1:26:04 Yeah. But there seem to be a sweet spot, maybe one to two, I wouldn't go above three, probably one point five to two millimolar range. That seems to be A level of ketones that safely does not produce a metabolic acidosis. So what we do see that when you get above three, it starts to change blood pH. So it seems to maybe overwhel the respiratory and renal compensation and your kidneys put out bicarb and then there's respiratory and renal compensation that kind of regulates your blood pH. But the animals that succumbed to keto acidosis and died from the keto nesters that we gave them in early studies.

1:26:45 had to do with the acidification of the blood. So it was just an overwhelming'cause ketones are acidic. And when you deliver it into an ester form, there's nothing to buffer that. When you give a ketone salt, the electrolytes are kind of like a buffer for that, right? So you have the metabolic effect, you have the changing of the brain neuropharmacology, and in bipolar, you throw antiepileptic drugs at bipolar patients and it's largely ineffective. So it makes sense that a ketogenic therapy would kind of

1:27:14 Work. for that. And the neuro inflammation too. So Things that trigger neuroinflammation and that could be That could be an infectious agent. That could be a virus. That could be, you know, T Gandhi. I mean, it could be like a bacteria. There there's various things that could cause psychiatric disorders. Various infectious agents create that neuroinflammation.

1:27:35 And then when someone has a seizure too. the inflammatory state of the brain gets much higher. So I think ketogenic therapies are working. Through multiple mechanisms, more or less like in synergy to produce that. It's not one mechanism. When we published the N L R P three f I got requests from Gen Entag and various pharmaceutical companies to go there

1:27:57 And give a talk on the mechanism so they could drugify and I would throw up like A big flow chart of all these mechanisms. And I think they would get frustrated and was like, Well, what tell us the mechanism so we can make a drug out of this. But I think the beauty of ketogenic therapies is that it's pleiotropic, which means it's many mechanisms working in synergy. You could say

1:28:20 Metformin, GLP one drugs. are working through metabolism and they're Kind of pleotropic also. Do you use either of those? I've experimented with metformin and that is a way for some patients to increase their ketone levels. So we've published on metformin from the context that it increases

1:28:41 Mitochondrial oxidative stress. It's a weak toxin to the liver. Most people didn't know that when we were studying that. And I think Metformin can enhance, increase AMP kinase, maybe increase insulin sensitivity, and has a very weak effect at reducing blood glucose if you have a normal glucose, but it does tend to increase

1:29:03 ketones a little bit, and I think there's about a hundred and fifty studies on clinical trials dot gov right now on metformin as a means to augment cancer therapy. So I think that could be a tool in the toolbox for some people. When I take it and I do really intense if I do an intense workout, I felt sick. An issue with metformin is it could produce lactic acidosis. It's producing lactic acidosis because it is a toxin to the liver. So it's sort of deenergizing the liver. But also when I took it up to two gram per day, I had a photosensitivity. So when I went outside, the sun gave me a rash. You mentioned on your wrist. Yeah. Am I making that up?

1:29:41 Yeah, yeah. It tend to correlate with that. And then I got off of it and then I experimented with it again and I'm in Florida and it was like May. It's like when the sun's really starting to crank, and then I just go outside all day and it's like, Where is this rash coming from? So it's a photosensitivity reaction that I got. And that kind of concerns me. So I never I have it, but I don't use it. May I ask you a quick question just related to Met Foreman for a second? I was looking back on notes on prior conversations and I think you mentioned Dr. Dale Bredson.

1:30:11 on an episode of STEM talk, but specifically for folks with the ABOE four genotype, like yours truly. Do you think metformin may be more interesting? But let's assume in my case Let's call me metabolically healthy. So maybe yes, maybe no. I remember a long time ago having a chat.

1:30:30 With Nav Chandal, I want to say. I might be getting the name slightly wrong from Northwestern. And he was like, Ah, if you're doing a bunch of exercise and getting your diet straight, he's like, I don't think that you're gonna see a lot of benefit, but he didn't have the Ape OE for information on me. And then Berber and I have written down for some reason. I'm just wondering if there's anything to either of those for Apo E four specifically.

1:30:53 Yeah, berberine is kind of like the It's pretty similar to Met Foreman's glucose lowering effect. So that's something that you can consider if you don't want to take metformin. I'm of the opinion that for the general population eating a standard American diet that, you know, is kind of averse to like working out and just Trying to really modify their diet, Metformin I think is a very

1:31:15 potentially effective drug for longevity. It's going to reduce blood glucose. Since most people are pre diabetic or you know have type two diabetes that are in their forties, fifties, and sixties. And it will reduce your incidents of cancer, specific kinds of cancer like pancreatic cancer. I think the data's

1:31:35 Kind of good on that. And I think it'll shift metabolic biomarkers. that we have historically good data on in the right direction. Does Bedforman do anything that Taking a GLP one.

1:31:49 Like Doesn't do. I mean, I guess I'm just wondering if there's an additive effect. They're well, they're totally different drugs, but people who Take metformin and one gram to two gram dose. Two grams is kinda high, but it when they do that, they tend to eat less calories. So it does create like a little bit of for me a GI issues, maybe a little bit loose stools from the beginning.

1:32:11 And that could, you know, be factoring in there. So it does tend to improve metabolic biomarkers across the board if you're trending towards metabolic Disregulation or metabolic syndrome. Yeah. A GLP one works essentially through caloric restriction and just decreasing appetite through in part a mild gastroparesis and decreasing

1:32:33 gastric emptying time, but also works on the brain and I think has a wide range of beneficial effects. I think it's it's a game changing drug that's gonna change the whole landscape of Metabolic therapies. Yeah. He seems to have a from what I've read, and maybe I don't want to overinterpret here, but potential neuroprotective effects, right? So That's the main reason I would be looking It's

1:32:56 Potentially Low dose GLP one. I like that you preface it with low dose because I think higher doses are Not studied enough. Long term.

1:33:06 to avert potential side effects that we don't know about, but Do you take berberine or Is it superfluous because you of the diet, you don't really need anything to lower. Lucose.

1:33:18 Yeah, I I've experimented with it and it did decrease my glucose in response to a meal. I did dihydroberberine, which is a more potent version. Uh Berberine. But Interestingly, after about a week I started to get a headache. And then I got off I don't know if it has a vasodial or it maybe it impacts liver metabolism in a way that was Who knows, maybe making decreasing my

1:33:42 caffeine metabolism. I mean that's these are things that come to mind. You still consume quite a bit of coffee, yeah? I do I fill this up. So this is metabolic mind.

1:33:53 Yeah. Actually Metabolic Mind is part of the Bazookis group metabolic psychiatry. So they they have you're one of these per day. Yeah. What is that? That's like Sixteen to twenty ounces. Twenty four. Something.

1:34:06 Twenty four ounces. Yeah, okay. It's a it metal it looks like a thermos, basically. Yeah, okay. Got it. Yeah, relatively strong coffee. I do you know, I do that and pour One cup and I usually finish it like about now and no caffeine. Yeah, caffeine at four or five PM is probably gonna disrupt. Sleep latency and

1:34:24 Mm-hmm. Sleep timing. But yeah. GLP one amazing class of drug. We're covering that now at med school. in our nutrition courses we're teaching and then the SGLT two inhibitors are also

1:34:37 A pretty interesting class of drug that I think has a lot of potential. So if someone trying to bring their glucose levels down, for example, trying to get that These are prescription drugs, so of course go to your doctor. But that's the pretty good lever to pull, especially if someone's like resistant to dropping their carbs if they're eating some carbs. And the GLP one and SGLT two are great. Well this is also

1:34:59 you know, tool in the tool kit with let's just say elderly patients who are Even if they wanted to comply may not have the mental faculty. to comply with ongoing And you can't have necessarily twenty four seven supervision. Prevent them from eating bagels.

1:35:16 Ha. Which maybe you can do. Just like all the meds in the morning and then one injection a week or whatever it might be. Do you take any supplements or medications for mitochondri with the explicit goal of mitochondrial health, or maybe just the side effect of mitochondrial health? Yeah, well I think ketones shine there.

1:35:35 Both the D and the L beta hydroxybutyrate. So that's like first and foremost, and We are doing research with NAD. These injectables? Well, I can't talk about, you know the research that we're doing in depth, but we're working with Metro International Biotech. So they have phase two and phase three trials for like Alzheimer's

1:35:55 There's NR, nicotinamide ribocy, nicotinamide mononucleotide. So the problem with those is that they're kind of The liver is pretty greedy and takes a lot of that, and then the muscles are kind of bre so a lot of it's maybe not getting to the brain. But If people just Google like M IB six two six, so that's one of their drug forms of NED, that's a stabilized form of NED, and then they have a whole suite of NAD molecules that most people don't know about, but are in experimental trials and we're doing some of those preclinical animal model work.

1:36:28 in our lab. So I do think for certain applications we didn't see an effect, but at the same time They are for applications like, you know, non alcoholic fatty liver disease, maybe Alzheimer's, maybe inflammatory disorders, improving If you used For a long period of time. markers of mitochondrial health.

1:36:49 I I think improved. So N A D People may know NAD is basically like a substrate for like the Sirtuins. And various enzymes. There's like five hundred different enzymes. Yeah, so

1:37:01 A class of proteins that are called sirtuins rely heavily on NAD. So this is like an important thing to consider And the Sirtuans just for folks who are like, Have I heard that before? I wanna say back in the day when Resveratrol was everywhere in the news and Supermouse and All you have to do is drink wine, but maybe twenty cases of wine. I mean that you know all of that stuff with transfer as veritrol that that's where the sirtuins popped up. Yeah. Yeah.

1:37:27 The Sirtuans are really heavily reliant on NAD. And NAD is involved in everything that we study, right? So like five to six hundred metabolic enzymes need NAD for fuel. So that's important to consider. And DNA repair is exclusively tied to NAD levels. So remember I mentioned like reductive stress with D beta hydroxybutyrate. Reductive stress means that the NAD to NADH ratio would drop. So you get more NADH relative to NAD. And that could be problematic because

1:38:03 the availability for NAD may not be there for Sirtuins and other so that you know a redox balance formulation. So that kinda feeds back. I don't want to get too far into that, but I think it is impacting the redox balance, which is Getting us to revisit the various ketogenic formulations and to study this in cell-based systems, animal models, it's hard to do in humans. You could do like a

1:38:30 Thirty-one phosphorus MRS if you have like a four or seven Tesla system like Harvard has. So this is one way to look at like phosphocreatin, ATP, pH and also NAD to NADH ratio. So this is one way. Actually, we do have that at our Alzheimer center, and that's on the list of to-do's. to look at this reductive kind of stress thing. So N A D I'm just I'd throwing that out there because I think N there's some a lot of criticism towards NAD now. That happens from time to time because moving

1:39:02 Science from cell based systems to animal models to humans, there's a massive learning curve there. We're learning that with some of the ketogenic agents. We're just at the cusp of really understanding The dosage, timing, scheduling, and form. of exogenous ketones, that's optimal. And it's going to vary dependent upon the situation that you're trying to treat and also individually. I think people are gonna have. So

1:39:27 That opens up this whole Personalized precision ketogenic metabolic therapy, or the NIH is throwing a lot of money on personalized medicine based on genetic markers and based on biomarkers that some of them that you can measure in real time, like continuous ketone monitoring, continuous Glucose and maybe lactate monitoring.

1:39:47 Yeah, that's very cool. One last supplement question because I'm looking back at past notes. And I'm Probably gonna mispronounce this, but Edebinone. Sort of more observable.

1:39:59 Version of Co q ten. Maybe that's a fair description. Maybe it isn't. Do you still take that or no longer? I think CoQ10 is on the short list of five supplements that I would recommend to people, although I don't take it. I do get quite a bit from the foods that I eat. I eat a lot of heart, liver, animal products that have kind of like CoQ ten in it, but if you're like on a statin, if you're on like metformin and other drugs. They could potentially deplete you and then CoQ Ten has a solid track record for like cardiovascular health.

1:40:29 So Idebonone is kind of a drug stabilized form of that and then When I discussed that on your podcast, that was in the context of something called the Deanna Protocol. The Deanna Protocol is after Deanna Tadone. She has ALS, she was diagnosed. Well over a decade ago was given, you know, two or three years to live. She's alive and well today. We're just like emailing yesterday. So

1:40:53 Diana todone had advanced ALS and then has been stabilized using the Diana protocol, which included at the time IDebonone, but I think it became a drug. So a Debonome became the standard of care for Friedrich's Ataxia, and then you couldn't get it like on Amazon. But I think Ubiquinol. or co q ten, it would be a a good substitute for that. And I don't use it myself, but I think that's if you're older in age and you have cardiovascular Heart problems like in your family.

1:41:21 However, with that said, we actually did Ubiquinol, we did high doses in our animal models and we saw some like kidney toxicity. We had some animals die and we did so But that was in rodent models. And we use again, we use like really high dose for oxygen toxicity. We've looked at everything under the sun, but it was this unexpected side effect. And then I went to the literature. And show that it's such a powerful antioxidant in some ways. And it maybe was concentrating in the kidneys. So there was a couple papers came up and then we think that that's why, you know, the animals may have died. We were using a mito Q like various forms that are like more mitochondrial specific. We're using like

1:41:59 More potent forms of the K ten. So it may not be to Similar to the uh commercially available. forms. What are the other supplements on that short list? You said four or five supplements. What are the other ones? Did I take yeah, so creatine monohydrate would be kind of the staple thing that I've used, you know, since I was, I don't know, a teenager.

1:42:19 First and foremost, exogenous ketones and the data is emerging on that. I think that's going to be like the next creatine. Or that but creatine. For Alzheimer's disease, we didn't talk about it, but a dosage of ten to even if you're larger, twenty grams, and that's not A misspeak there, twenty grams of creatine. Spread out, you know, maybe five grams three to four times a day for advanced Alzheimer's if you can tolerate it.

1:42:42 Micronized tomorrow. I'm taking twenty grams today just because I didn't get very good sleep last night. I just find it to help with recovering from Let's call it sleep deprivation. But yeah. Gotta watch the split dosing.

1:42:56 Vitamin D, but you have to measure that like in your lab. So you want that to be you don't want it like over a hundred, right? So you want vitamin D. levels that are probably like sixty to eighty. Would be A good level vitamin D on and getting that checked. But I think you should check it first. It's weird. I live in Florida. I get tons of sun, but if I'm not supplementing vitamin D, I trend to be like low

1:43:21 thirties it could be trend, but so when I supplement it, I basically stay in the mid sixties to seventies. So vitamin D and Melatonin, I think is a great neuroprotective antioxidant supplement to take at nighttime and I don't take omega three supplements but just because I did Ronda Patrick, you know, connected me with the omega three guy and I tried the omega quant and my DHA levels and EPA levels were off the charts. Out of curiosity, I got off a fish for like a month or so and

1:43:55 I went down to normal ranges and then I tried Nordic Naturals, which it was a company that reached out to me and I was like, Okay, well I'll Remove. Omega three is from my diet and then add it back in with a dose and it pop me back up to a level similar to if I'm eating like tons of sardines per day. So if you don't like sardines and you don't like eating a lot of fish, I think Nordic Naturals is probably like one of the go to brands, you know. I'm not paid to say that or anything, but They're legit, but you could do the Omega Quant test and I think There's so much data on EPA and DHA that I think ultimately

1:44:29 The omega three levels will be part of standard blood work. Like there's so much data emerging on that that I think probably within the next ten years, like when you get comprehensive metabolic panel, C B C, like that D H A and E P A will probably be Added to that. All right, Don Well, we could go for

1:44:45 Many more hours, I am sure, but Let's Start to land the plan for this round. And I do want to ask, of course, if there's anything else that you'd like to mention or point people to Anything you'd like to recommend, uh formal complaints you'd like to lodge.

1:45:02 People he'd like to secure in front of a large audience. No, I'm kidding. But uh anything that you would like to say or point people to? Any resources? Anything that you're up to. Where they can find you anything at all? Yeah, I just want to you know mention Keto Nutrition. That's our informational website, Keto Nutrition.org. We've hosted a conference where many people you know, Dr. Valter Longo, Rhonda Patrick, who's been the keynote speakers, that's the Metabolic Health Summit.

1:45:30 Uh that's been the conference. Uh, and that is run by Metabolic Health Initiative. So I direct people to Metabolic Health Initiative and it's kind of run by three of us. My colleagues, Dr. Angela Poth and Victoria Field, sort of run that show. I kind of tag on for the ride. But that's an ACCME accredited medical education platform. So everything that we're talking about here. We have speakers and we create a medical education platform so people can learn about metabolic psychiatry, people can learn about metabolic based therapies and metabolic drugs like GLP one drugs and and hormone optimization and things like that. So I would mention that. The brand of ketones that I use that often get asked is Audacious Nutrition Keto Starch. So that evolved out of our work with cancer, nerve degeneration and seizures.

1:46:18 We're doing work at you know Bert Alzheimer Center on probably twenty or more ketogenic compounds in development that are mostly alcohol free So I think all of them are actually and we have some really interesting studies on Alzheimer's and a lot of other. So hopefully in the next year be able to share some of that pre clinical animal model work. hyperbaric oxygen. So we have a twenty eight million dollar study. Huge. Uh yeah, at the University of South Florida. I am just peripherally involved in that, or just know people running that. And it's

1:46:52 essentially evolved out of the DOD work that looked at the muddy waters of hyperbaric oxygen therapy. Uh for that. It's a good way to put it, the muddy waters. Yeah, I have been part of reviewing grants and also manuscripts, and I think there's a lot of interesting studies that's going to emerge by the time this airs, I think they will be on PubMed.

1:47:13 Essentially showing that Hyperbaric oxygen therapy protocols more mild hyperbaric oxygen forty to sixty sessions in people that had traumatic brain injury. A decade ago. can enhance cognitive function, reaction time and

1:47:31 a wide variety of metrics associated with brain function. So I think this work coming out of Israel, I'd like to see it replicated. I would like to see the work that's different at the University of South Florida is that it's very innovative and that it's using a sham instead of using hyperbaric air as the control. They basically pulse pressure in the beginning to make people think they're being pressurized and at the end, so their ears pop a little bit. And you know, I don't know every it's blinded, you know, people don't know even what they're getting. If you question them, they don't know if they're getting hyperbaric oxygen. But I do think that Oxygen is a powerful drug and I and I'm excited about that research, if you ask me. I'm excited if it proves it or disproves it, you know, I think we're gonna get

1:48:15 An unambiguous answer to this question about hyperbaric oxygen for traumatic brain injury in people with and without post traumatic stress syndrome. So My thing is that If they put patients on ketone metabolic therapy, that would augment and enhance hyperbaric oxygen therapy and decrease the potential for risk. of an oxygen toxicity seizure, which goes up, right? If you've had a traumatic brain injury.

1:48:40 your risk of oxygen toxicity seizure would increase. Now this is m pretty specific to military, or what are we uh talking about? They're all they're all vets, and if they do find out that they get a uh a beneficial effect from that, then after the the experiment, they'll be able to get that for free service. So there's six quarter to half a million dollar hyperbaric chambers. So the hard shell chambers, you know, there's six of them in this facility.

1:49:07 And it's the most Elaborate hyperbaric auction. therapy study that has ever been done. So and it'll answer the question about the efficacy. So that's ongoing now. And I'm excited about that. I'm also excited about potentially using that facility. Because it's next to the Moffitt Cancer Center for patients that are undergoing

1:49:24 various cancer treatments that could be enhanced with hyperbaric oxygen therapy because it augments the immune system and It's a s actually the an FDA approved application for radiation necrosis. So if you've had radiation, then your insurance would actually cover it. But it can enhance certain therapies that we're working on. Yeah. Amazing.

1:49:42 All right, well we will link to all of those things. In the show notes. As always, and I encourage people to check all those out. I'm gonna check all of them out. And Tom.

1:49:54 Thanks so much for the time, as always. I took a ton of notes. I have even maybe even more questions. On top of that for more text messages. Sorry in advance. And uh so nice to see you again. Yeah, you too, Tim. Yeah. Thank you for having me on. I appreciate it. Absolutely. And uh folks

1:50:12 Show notes can be found at Tim.blog slash podcast. Just search. Dom or Dominic and a lot of them will pop up. Just look for the most recent. And until next time. Be a bit kinder than is necessary. It matters, it helps, to others and to yourself.

1:50:28 And as always, thanks for tuning in. Hey guys, this is Tim again, just one more thing before you take off, and that is Five Bullet Friday. Would you enjoy getting a short email from me every Friday that provides a little fun before the weekend? Between one and a half and two million people subscribe to my free newsletter, my super short newsletter called Five Bullet Friday. Easy to sign up, easy to cancel. It is basically a half page that I send out every Friday to share the coolest things I've found or discovered or have started exploring over that week. It's kind of like my diary of cool things. It often includes articles I'm reading, books I'm reading. albums perhaps, gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends, including a lot of podcast guests, and these strange esoteric things end up in my field, and then I test them and then I share them with you. So if that sounds fun, again, it's very short, a little tiny bite of goodness before you head off for the weekend, something to think about. If you'd like to try it out, just go to Tim.blog slash Friday. Type that into your browser, Tim.blog slash.

1:51:35 Friday, drop in your email and you'll get the very next one. Thanks for listening. Creatine isn't just for muscle, it turns out. It's essential daily fuel for your brain, your body, and long-term performance. For me, I have Alzheimer's and dementia risk in my family. The cognitive benefits are the reason I take creatine every single day. And it also seems there's some evidence to support if you don't get enough sleep. that you can use creatine to compensate to recover from that. I also use it for that purpose. And today's episode sponsor, Mementous, is the gold standard in creatine. There's a lot of BS floating around. lot of questionable creatine, but I choose them why? Because they source Creapeure Creatine, the purest, most effective creatine monohydrate available, single sourced from Germany and not cut with fillers or junk, which is hard to avoid otherwise. Their new lemon travel packs make consistency easy.

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