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you

00:03
Hey everyone, it's Mikki here. You're listening to Mikkipedia, and today on the podcast, I speak to returning guest, Dr. Dom Dagostino. Those of you who probably know, Dom is a leading researcher in metabolic health, ketogenic diets, and performance optimization. Dom has been at the forefront of exploring how nutrition, particularly low-carb and ketogenic strategies, impacts brain health, endurance performance, cancer metabolism, and longevity.

00:33
And in this episode, Dom and I dive into two major topics that have been gaining traction in the health and nutrition space. First one is are you low as a metabolic sweetener? And also the latest research on the ketogenic diets effects on lipids, gut health and glucose metabolism as it compares to just a low sugar diet.

00:56
So we begin by unpacking alulose, which is a rare sugar that's rapidly growing in popularity within the low carb and metabolic health community. It would be termed a non-nutritive sweetener. However, it has different impacts on metabolism compared to the likes of, say, stevia or monk fruit and things like that. So Dom and I do a deep dive into it and some of the unique metabolic.

01:21
benefits of it. And then we shift to the ketogenic diet and explore a recent study that examined its effect on metabolic health, gut microbiome and cardiovascular numbers. We talk about the implications of the ketogenic diet and how we might fine tune a ketogenic approach for long term health. But importantly, we bring up a number of not just limitations, but discussion points that that paper sort of brought up. And of course I will link to both papers.

01:49
in the show notes. So for anyone interested in the cutting edge of metabolic science, whether it's role of emerging sweeteners or the nuances of a ketogenic diet, I think this episode is packed with valuable insights for you. Dr. Dom Dagostino is a leading researcher in the fields of metabolic health, ketogenic nutrition and performance science. As an associate professor at the University of South Florida in the Department of Molecular Pharmacology and Physiology,

02:18
His work focuses on the neuroprotective and therapeutic applications of ketogenic diets, exogenous ketones and metabolic therapies for conditions such as epilepsy, cancer and neurodegenerative diseases. Dom's research spans human performance, space medicine and metabolic resilience, with collaborations extending to NASA, the Department of Defence and leading medical institutions. In addition to his academic and research work, he has widely recognised

02:47
for his expertise in low-carb and ketogenic science, frequently sharing insights on not only his own podcast, but on other podcast appearances, social media, and public talks. He has conducted extensive N equals one experiments on metabolic biomarkers, dietary interventions, and the effects of ketones and alternative sweeteners like allulose, helping bridge the gap between scientific research and real-world application.

03:14
Dom is also on the editorial board of multiple scientific journals, has published extensively in peer-reviewed literature, is a sought after speaker in the area of metabolic health, longevity and human optimization, and also is one of the co-founders of the Metabolic Initiative. That brings us to the Metabolic Health Summit and of course the Metabolic Link, his podcast. I will put links to where you can find Dom and his resources in the show notes.

03:41
Before we crack on into the interview though, I would like to remind you that the best way to support this podcast is to hit the subscribe button on your favourite podcast listening platform. That increases the visibility of Micopedia and amongst literally thousands of other podcasts out there. So more people get to listen to the guests that I have on the show. Alright team, for now though, please enjoy this interview I had with Dom Dagostino.

04:12
Thank you so much for taking time with me this morning. I am, I absolutely love all of the work that you guys put out and you're across so many different topics in keto nutrition and it seems to be gaining a lot of traction, particularly in the last couple of years and also with some innovative products sort of to market, like have you come across the David Bar, the David protein bar?

04:40
and I tested it and it didn't test very well with my CGM. Ah, wow. But I think the taste was good and I think it's like good for, it's better than a candy bar, I'll say that. I think it's probably close to like a Quest bar. It's like a little bit better than a Quest bar, but at the same time, not a whole lot better. And from a CGM perspective, it's either identical or maybe even a higher.

05:03
And I was kind of surprised because it did have allulose in it, but it also had some other forms of, it had like tapioca starch and some other things that I think. I think it's got polydextrose as well or something, which I don't know what effect that has. They sent me different ones and like the blueberry one, or maybe the chocolate, one of them didn't go up too, but I think the birthday cake one was the first one I tested. And I was like, oh man, look at this. I was going to post about it, but I didn't want to.

05:32
I was going to do a comparison, but I was like, ah, I feel it looks like it's dissing the company. They're nice enough to send it to me. I guess not promoting them is my way of saying, okay, I wasn't impressed with it. Yeah, yeah. It's what you don't say that makes a big difference. That's super interesting actually, because we don't get them in New Zealand. They only ship to the States, and I'm in the States right now. I thought, oh, I'll just grab a couple of boxes. Because they've got like 28...

06:00
they've got 28 grams of protein. And then of course, they've got the alulose, which is what I want to chat to you. One of the things I want to chat to you about today. One of the things that really surprises me Dom is that with all of the protein and of course, they've got the carbohydrate and a little bit of fat, but it only comes out at 150 calories per bar. And I'm always like, I don't understand nutrition label maths, like I should because, you know, like I'm

06:27
You don't have to be like a brainiac to understand it, but you just do the maths and you add up all the numbers and it should come out at what the label says. But 150 calories seems a little light for the amount of protein and the amount of carbohydrates. So is that to do with the way that allulose is counted as part of the label? Yeah, allulose, I'm working on systematic review. So allulose is largely excreted. It's not...

06:56
It's not even like metabolized much in the gut, although it does contribute probably. There's a little bit of metabolism. But generally speaking, it's about 0.2 to 0.4 grams per kilogram. So it's like 90% less calories than like sugar. You know, it is sugar, you know, and that's why there's a range there too, because it varied a little bit, but it was like, you know, point it's definitely less than one gram.

07:25
one calorie per gram and probably about 0.2, probably closer to 0.2, just because it circulates and then our kidneys excrete it and there's a little bit of fermentation like in the gut. And yeah, it has some interesting properties. So yeah, we can jump into that discussion if you want to start there. Yeah, that would be great actually, because of course we need to back the truck up and actually let people know what it is because it's gaining traction, but it's not actually that well known. So can we like just kick off with

07:54
what it is and how it differs from the other sweeteners like stevia, milk fruit, those kind of, and of course the sugar, alcohols, et cetera. Okay, yeah, sure. I think that was part of your question too. Yeah, so yeah, I get asked quite frequently, like what is alulose? How does it differ from other sweeteners like sugar and stevia and things like that? So upfront, that inspired...

08:15
Me, working with, we have a mandatory nutrition course with the medical students at USF and they're writing a systematic review on this topic comparing allulose to stevia and to erythritol and other things. So allulose is superior to other natural sweeteners in many ways.

08:36
And we wanted to focus on the natural sweeteners because we do think that they, that is kind of like the future. I think especially with the new administration, I think things will trend to go in that direction to using natural sweeteners for sugar-free products. So it's superior in regards to, has a non-glycemic effect and it's has no insulin response essentially, and you can bake with it and it's found in nature. It's a rare sugar.

09:06
jackfruit, which is around here in Florida, figs and raisins are high. And it's essentially, it's an epimer of fructose. So it almost looks identical, but it's like, uh, there's, there's an enzyme that's actually naturally found in, in nature that converts, that makes a small, uh, adjustment. There's an antimer and epimer and an epimer is actually like even closer to it. But.

09:34
But a single switch at one of the carbons prevents allulose from being metabolized by certain enzymes. So there's an epimerase enzyme that converts fructose. And that's actually how I get a lot of questions. How is allulose made? Is it synthetically made? Where does it come from? There's different ways to make allulose. The mass scale to do it would be to take

10:00
corn or sugar cane is usually, I think sugar cane is often used. And then you take, or some kind of starch, right? You take some kind of starch and then you make fructose. And then from fructose, you can make allulose with epimerase, with just adding like a natural, you know, what's found in nature, different enzymes in a vat. Or you could do, you could take natural sugars. And this is how it's made on a small scale.

10:27
Just natural sugars from fruit and things like that, and whether jackfruit, figs, raisins, or whatever, and convert and add enzymes into the vat, and then you get the conversion of fructose to more allulose. So Whitney said that it's high in, you mentioned jackfruit and figs, it's not that they contain allulose, but they contain an enzyme that helps convert the starch, is that what you're saying? Oh, okay, yeah, good question. So,

10:55
Allulose is a rare sugar, which means that it's found in nature, but it's relatively trace amounts compared to glucose. So it's just found in relatively higher concentrations in certain fruit. I think kiwi, jackfruit, figs, raisins, it's even found in wheat. You can get it in wheat, I think. I think actually some commercial industries, I saw some papers where that's actually how they're making it now.

11:23
So I know, like disclosure, I'm a consultant for RX Sugar. And they have Agulose and they don't get it from wheat. They get it from like a non-GMO source. So they're very particular about sourcing it. And they're investigating new ways to just make it, to bring the price point down in ways that is economical, sustainable, non-GMO and kind of checks all the boxes. So that's a process, but.

11:50
but they stick to that. And then, yeah, so just it's important to check if the source of your allulose, I think that's important just from an economical point of view or environmental point of view. But yeah, so allulose is an epimer fructose, it's very similar, it gets transported across the intestinal lining by the same transporter that fructose uses, the GLUT5 transporter uses that. And so our project,

12:20
with allulose is we don't have time to talk about it, but some cancer cells like colon cancer cells, even lung, they grow very rapidly in the presence of fructose. Fructose can drive cancer growth and proliferation, and it overexpresses the five. One idea is to give allulose, and when the cancer cells suck up allulose, they can't use it as for fuel. We try to grow...

12:49
different cancer cell lines in fructose and they grow quite rapidly. If we put allulose on, which is just an epimer, it looks the same. It kills everything. So it's actually very interested in the anti-cancer effects of allulose. That's what got me into allulose research. I was like, oh, it uses the GLUT5. And I knew certain cancer cells really grow like crazy in the presence of fructose. So this is sort of like a fructose antagonist in that.

13:18
So, I could do a whole other podcast on that. But it has some interesting effects on, you know, no effect on glucose, insulin elevation. And I think what's most important is that when you add allulose to carbohydrates, it reduces the glycemic and insulin response from a predetermined amount of carbohydrate. So I was skeptical about that, but multiple lines of evidence in independent labs have shown that.

13:46
That is a really curious observation. So it's like the question, how does it do that? It does it through probably a number of mechanisms. Maybe it inhibits like a sucrase enzyme. It may compete at the level of the intestinal wall. And it also increases GLP-1, which could delay gastric absorption in a way that could just prevent...but the whole, the area under the curve is less. So that's very interesting and I think one of the functional properties of Allulose.

14:16
It's so interesting, Dom. So you do a number of experiments, obviously, and we just chatted about the David Bar. So I'm just like not to hark on about the figs, but I am sort of interested in this. Like when you test like a natural product that contains higher concentrations of allulose, is that noticeable? Like would you expect figs to really raise your blood sugar? But actually they don't. And you're sort of like, oh, why would that be? But then you find out they've got allulose and you're like...

14:45
Okay, makes a bit of sense. Is there enough of allulose in those kind of figs and raisins to mean that the expected blood sugar response isn't seen? I would say no. I think even in fruits that are quote unquote high in allulose, it's still a rare sugar, and that makes it a relatively trace amount.

15:07
It could be it's less than 10% for sure. Okay, okay. It was like 4% alula and that was like relatively high and I'm sure like wheat is definitely less than like 0.1% probably but now like people are looking at wheat as a source of alulas. Yeah, okay. But it's you know, the starch from that that can be converted to fructose and then a simple natural enzymatic reaction can

15:36
for sweeteners because it just checks so many boxes. And, you know, of course other people have talked about it. I think it was with Peter and Tia, we were at Quest Nutrition and they were, they were experimenting with this stuff, like back in 2014. And we were trying it. I remember testing it. Oh, I remember not having a good experience. I mean, honestly, the first time I just took, I was like dumping lots of it into my coffee and I was like, oh wow, this is great. And I was like reading it up on it. It seems like too good to be true. And then my gut started to

16:04
grumble about an hour later and I realized that there's a threshold. And I think that threshold is something like, I have to go back to the literature, but for me it's about 20 grams to 30 grams per day. Yeah. Okay. Interesting. 2 to 0.3 grams per kilogram, I guess, if I'm doing my math right. Yeah.

16:24
And what I found is that, you know, as I use Allulose, you build up more of a GI tolerance. And I think it's adjusting the gut microbiome in ways that you absorb it better and things like that. And now I can tolerate quite a bit of it. I can bake things with it, put it in like a variety of different things. And I have no GI issues. It checks the box from the baking perspective, too. And I know because it browns just like sugar gets incorporated, but it's about 70% as sweet.

16:52
So if you're baking with it, you might want to do a pinch of like monk fruit or something like that just to give it a little kick up if you like, or a lot of people are just trending to just less hyper sweet. That's a good thing too. Yeah, sure. And because it doesn't, did you say there's not a lot of fermentation? So from a gut perspective, even though you need to build up tolerance, people might actually respond a bit more favorably even if they have issues with like sugar alcohols and things like that. Yeah. So.

17:21
Xylitol and erythritol, so we did a deep dive on this with our systematic review, it's not published yet, are less tolerable, like at least in studies, than allulose. Xylitol came out and then everyone got, and then erythritol was a more tolerable form of a sugar alcohol, and that can kind of wreak havoc for me too if I get too much of it. But yeah, it's quite, it's a lot different. I mean, it's a monosaccharide, so allulose is...

17:50
It's a simpler compound. It's got a very well-known defined transporter. It's very predictable. It's found in nature. I mean, there's a lot of... It has a lot of things going for it, but my initial experience with it over 10 years ago was like, oh, this is not going to work because of GI. But when you take allulose, I think I consumed a lot of it on an empty stomach with coffee. But if you incorporate allulose with food,

18:18
then that seems to make it much, much more tolerable. So I think, I do think it's in many ways the solution for sugar, you know, or your sucre, incorporating it into food and can help people wean off sugar and it's fantastic for diabetics. Yeah, I found this super interesting. I listened to the Metabolic Health Summit conference panel on it last year, and there were a number of people, you were obviously on the panel, there was Ben Bickman, I think Andrew Kutnick was there, Richard Johnson.

18:48
a couple of others I can't recall, but they were talking about the different use cases that they've experienced with it. And I think someone, a member of the audience also mentioned that he's a physician and he's using it to help transition his patients off GLP-1 agonist medication. So like how does that- Very effectively too, yeah. Yeah, yeah. So how does that work, Dom? Like, I mean, you did mention that it increased

19:17
sort of replace a medication, it wouldn't have the same physiological effects, would it? No, it's, I guess if you want to use the term, it's a GLP-1 secretagogue. So it actually stimulates various pathways that result in the production and the release of GLP-1. And this first came out in a Nature Medicine paper years ago, like in maybe over five years ago. And the Nature Medicine

19:47
an equivalent of me taking, I think, 25 to 30 grams of it at a single dose. So that's a big dose, right? But what was really interesting is that the GLP-1 levels in the blood went up 500%. So, okay, things in perspective, when you inject yourself with GLP-1, like ozephyc, I looked into this, that would be much higher. It would be something like 2000%. So, but it's like...

20:16
Well, I guess a new trend is microdosing GLP-1s now. So it's like, it's actually, maybe you can think about it. A GLP secretagogue is kind of like microdosing GLP-1. To put it in perspective, when you eat a steak, your body also releases GLP-1. And I've not seen a study where they can pair allulose with eating like a ribeye or something. But there is some data on that, and it's kind of like two to 300%, at least in humans.

20:43
So we're talking about something that's stimulating a satiety hormone. Yeah. There's good science behind it. They've worked out some of the mechanisms. There's human studies sort of backing that now, but we do need more randomized controlled studies. We also need more randomized controlled studies long-term for allulose on the sustainability of it, but it's got a lot of things going for it. And it gets around like the whole idea of like something artificial, like aspartame super.

21:13
saccharin, ACE-K, those kinds of things. And I think you had a question too about like, so that's a GLP-1 and that's a pretty hot area of research now. Yeah. Like I think there's other things like that you could also take that could be, could release GLP-1s or just plant-based compounds that could do it. But, oh yeah, you mentioned the physician that, and I have quite a few emails from physicians that that's part of their routine now, so they get,

21:40
They get their patients on GLP-1, like relatively high dose until they make their ideal weight. They wean them off. Sometimes their insurance doesn't cover them. So they have to come off. But the off-ramp, so we're very good at putting people on GLP-1s, but we don't have a framework for an off-ramp to get people on off GLP-1s. But what we do know is that, and many clinicians have told me this, like even people that are out there talking about this, Gabrielle Lyon was one.

22:09
I know there's like at least a half dozen that have reported to me. I've asked them this question and they said they have no problem getting people off GLP one. If they incorporate things like, you know, just a high protein keto diet, allulose, you know, things and they maintain, you know, some type of framework with their nutrition. They could lose lean body mass. They maintain a favorable body composition, you know, even when they get off GLP one, there might be a little bit of struggle in the beginning.

22:38
And, but, but generally speaking, it's possible to do it. And I think, I think that's, should be an emerging area of research. Like, you know, getting people a healthy way, GLP ones is just one tool in the toolbox. It's very effective, but then a lot of research should be on getting people off these drugs because they do have side effects. And if we do have a framework and a successful operant ramp that we could, you know, administer, like there should be randomized control trials on.

23:07
Like there should be like people, there should be big studies on this. Because yeah, I get, I do get emails from people that are panicking because their, you know, their insurance doesn't cover it anymore. They can't afford it, but it was effective for them. Yeah. And also if you just think about weight loss as a thing like losing weight for a lot of people is relatively simple. And I don't want to say it's easy because I know that people struggle, but actually that's it.

23:34
that's not the hard part. The hard part is keeping it off. So I guess GLP-1 or not, having tools that you know that you can use that helps you in that weight maintenance. Like this is like another like a good use case for things that might help with appetite control and the rest of it. Yeah, like, you know, centralized protein, fiber, it's really important. We can have a whole discussion about that. And then holding yourself accountable and actually

24:03
using an app that is a tracker or just in our nutrition class, it was kind of interesting to find that one of the best tools was just someone just checking in, checking their weight once a week. And it's like, oh, like, okay, I'm going to cut my count. Okay, it's like, oh, my weight stayed the same. I don't want to, you know, if it went down that that weekly motivation can allow them like on the weekend, for example, to kind of set the stage for how they're going to eat during

24:33
Or I think people can get a lot of value by using a macro tracker that has like a little sliding function, uh, the carbon app lane. Norton has that. He's a friend of mine. You know, I know that works because people have, you know, connected, have been using it and, but I don't like tracking. So it's like something that I'm not going to do. I find it very tedious, but I've used that app and other apps. And if I do it for two weeks.

25:01
I never, I, this is what I eat in two weeks is what I'm going to eat. So it's like, I put all my meals in there and then I know what the macros are and I know what the calories are. And then I can just, that just sets a stage for what I, I know I need to do. Yeah. You know, so if people, it's just like a CGM, like you could use a CGM for two weeks and it's incredibly insightful. Like I really no idea how many calories I was eating until I really tracked everything. And I was like, well.

25:26
eating 600 to 700 more calories than I thought I was eating. Some days well over 4000, unlike real active days. So that was surprising to me and it also gave me a framework for the kinds of fats, the types of fats I was eating and I think everybody should do that. And it doesn't have to be a laborious tedious thing. You can just do it for the first two weeks or so. I know. People are really for whatever reason

25:55
to it, but I agree with you, you can learn so much and it's you have to be quite rigorous. Like it's not just looking at something going, oh, I think that's about half a cup. It's like literally weighing it on scales, which I think, you know, it is important. Like, I think people talk about the effort involved, but actually it's worth the effort. Like your health is worth the effort and you should relish the opportunity to put time into it is how I like to frame it for my clients. And I mean, they don't always run with it,

26:25
try my best to sort of suggest that they do. And many times they could, you know, it's fun for them to like have that sense of control and over their destiny and their, you know, their body composition changes and that, you know, here are my macros, here are my numbers, and I can adjust either, I can adjust these things to look like this or look like that or whatever. So it becomes...

26:49
You know, and you can't outrun a bad diet too. So no matter how much you exercise, lift weights or whatever, the biggest by far lever to pull is that's why like bodybuilders and fitness athletes are like obsessed with nutrition. They have to be because that is what makes the magic happen, you know, like training is kind of like a no brainer kind of thing. Uh, I mean, you can get technical from different aspects if you're powerlifting or whatever, but, uh,

27:14
But generally speaking, it's the nutrition that plays the biggest role in our overall health and our body competition. Yeah, 100%. We have to use the basics. It's important to do that. Yeah, for sure. And you know, it's interesting, Dom, and I'd love to move on to the next thing I wanted to talk to you about, which was a paper that was released looking at the ketogenic diet versus a low free sugar diet. So everyone always wants to know what is the best diet.

27:41
I mean, there's no one best diet, right? Because it really depends on the use case, et cetera. But for whatever reason, a ketogenic or a low carb diet continually gets sort of thrown under the bus when it comes to poor outcomes or it's not suitable for X, Y, Z. And it almost seems deliberate, even by really smart scientists to almost ignore a lot of the beneficial things that.

28:07
that can happen or just to highlight some transient potential negatives which aren't actually the main outcomes. And I guess what I'm talking about is the Javier Gonzales paper looking at just removing free sugar versus a low carb diet. And you guys did a really good journal club on it on the metabolic link podcast. So can we just chat a little bit about that paper and actually just why first I'm really curious.

28:37
what your thoughts are on how people continue to throw keto under the bus in the nutrition field. These are smart people, but for whatever reason, it seems like they, I don't know, they get put out by it. Yeah, I think we've kind of brought it on to ourselves sometimes because keto does in many ways get over marketed. It gets bastardized if you want to use that as, you know, there's a lot of keto products out there that are not keto.

29:04
Um, and, uh, there, the research is lacking in regard to the comparison, the benefits from, you know, other types of diets in regard to long-term cardio metabolic outcomes. So I'll say that, uh, but, and we can talk about that too. So most of the ketogenic diet studies, I got into it because of its powerful effect on seizures and on epilepsy.

29:31
So many people say there's nothing magical about the ketogenic diet. It doesn't, you know, it's just, it's calorie control. But that's not the case because you could, there's no other diet where you follow the diet that it changes the neuropharmacology of your brain in a way that prevents seizures across essentially pretty much all seizure types, whether it's absent seizures or temporal lobe epilepsy or glucose transporter type 1 deficiency syndrome, like a neuro metabolic disease.

30:01
And in that case, it's kind of specific too, because there are inborn errors in metabolism that cause, and this gets, I'm kind of getting into like the clinical, the outside applications too, that there are different disorders that we study in the lab that are inborn errors in metabolism. For example, a deficiency of the Glut1 transporter at the level of the blood-brain barrier. When...

30:24
When people who have this are in a state of ketosis, the ketones then feed the brain a source of energy and it re-energizes their brain. As we age, our ability to metabolize glucose as an energy source becomes quite deficient. So that's due to a number of different things. Pyruvate dehydrogenates complex, the glut-3 transporter, but it's pretty much ubiquitous. Phenotype.

30:49
for, it's actually a hallmark characteristic in Alzheimer's disease and age-related dementia is glucose hypometabolism. As we age, our ability to use ketones does not change. So what that means is that, you know, as we get older, if we follow a strategy that elevates and sustains ketone levels, we are feeding our brain an alternative form of energy, and there are many benefits to that. So we've studied not only the energetic effects, but the epigenetic effects, like signaling the anti-inflammatory effects.

31:19
So that's like important when you consume ketones, like a source at the ketogenic diet or exogenous ketones, you have an acute scenario and that's largely how these things are kind of studied and then the long-term effects of the elevation of that metabolite affecting signaling pathways that have more of a prolonged beneficial effects. So yeah, so. Sorry, can I just interrupt the mask?

31:43
You often hear, you know, we lose muscle mass, we start losing muscle mass at like the age of 35, etc. So there are, you know, specific timelines. Like at what age do we start seeing these changes in the brain? Like is there sort of, do we know that information? Like is it in our 30s, our 40s? Like when does it start becoming more obvious, I suppose, that we're unable to use glucose to the same effect? Yeah, there's a lot of individual variability.

32:09
And also a little bit of genetics in there. If you're APOE4 homozygous, for example, like, you know, you could start having dementia in your 40s and 50s. So that varies. But I think one could say that we reach our peak in like maybe our late teens, early 20s and things start to go downhill after about 30 or so. But we acquire

32:35
Our brain, there's still plasticity in our brain and we become smarter in different ways. Although from the context of what the subject I teach is called long-term potentiation, like for example, in the hippocampus where there's like early LTP and late LTP and the mechanisms surrounding that, whether it's ampereceptor activation or protein synthesis to create new synapses or whatever, like that's all jacked up and like super efficient.

33:03
and at 17, 18, 19, up until, you know, our early 20s, and then tends to taper off. And some of that's under hormonal regulation. So if our hormones drop, even things like androgen, estrogen, and various, but also we can mitigate a lot of that through exercise and our metabolic health. So that's the whole, that's a big concept. And exercising increases different growth factors that help to enhance our learning and memory.

33:29
and restore those processes perhaps even above baseline if they were. If you follow an unhealthy diet in your teens and early 20s and then start running, for example, and exercising in your 30s and 40s, you could increase NGF and BDNF-induced neuroplasticity and long-term potentiation above and beyond than decades earlier. So this is known. And typically, if you couple that with...

33:57
some type of learning activity that you're very engaged with and you're excited about. Whenever we have like a sympathetic or if we're personally engaged and emotionally interested in the topic that we're trying to learn and really engage, that's also a profound stimulus for long-term potentiation and memory. And if we do that in the context of doing exercise,

34:23
aerobic exercise, which I know I should do and I don't do enough of, but also lifting probably contributes a little bit to that. And our nutrition is on point, especially with sufficient amounts of protein, then that's the perfect scenario. And following a nutritional protocol that optimizes cardiometabolic biomarkers, because whatever's healthy, the things that are healthy for the heart are equally healthy for the brain. So when we talk about brain health, we're really talking about, when we're talking about heart health, we're talking about brain health.

34:53
because the two are pretty much non-distinguishable. In regards to the interventions and biomarkers we should be tracking for cardiovascular health, it directly correlates to brain health. Oh, that's interesting because what I also saw when I was preparing for our interview was you reposted a paper about ketones in the heart actually in cardiovascular, the cardiovascular system and how they either protect heart tissue or how do they...

35:22
help in the situation of a heart attack? Is that correct? Yeah, yeah. Ketones are very cardio protective and there's several labs that just that's kind of what they focus on. And some of the original research published by Dr. Richard Veach, I'm thinking about a paper in 1995, was the earliest most convincing paper where they use like a bit of a draconian kind of...

35:51
experimental preparation, but they kind of take the heart out and it's pumping from like an organism and then they can feed it different substrates and look at the hydraulic efficiency of the heart under different metabolic substrates, you know, with and without insulin and some other variables too. And they established that the hydraulic efficiency of the heart was 25 to maybe 28% more efficient in the context of burning ketones, like relative to glucose. Oh, wow.

36:17
So that had to do with the delta G of ATP hydrolysis. So essentially, you can make more ATP per carbon or oxygen molecule relative to the source that you're feeding it. And then the heart actually doesn't use a whole lot of glucose relative to fatty acids. So the heart loves fatty acids for fuel. It loves ketones. And when we're in a state of ketosis that...

36:45
the ketones can rescue a failing heart. So if you have pre-existing heart damage, then being in a state of ketosis can help rescue cardiac efficiency and in some cases perhaps help to restore cardiac function. And that could be a direct effect, but I think it's more like an indirect effect. So for example, when our ketones are elevated,

37:10
that has effects on the endothelial function. When your ketones are elevated, it increases adenosine. Adenosine receptor signaling tends to relax blood vessels. So if you give exogenous ketones acutely, or if you fast and get into a state of ketosis, brain blood flow goes up anywhere from like 20 to 40%. And...

37:32
You know, we've shown, we have to, one of my PhD students did a whole dissertation on like blood flow to ischemic wounds with ketosis. Do you use Doppler blood flow measurements? We see like an increased perfusion in that. And I started getting interested in adenosine. So acutely, if we take, if we elevate ketones, fasting, dietary, or exogenous ketones, that's increasing blood flow. And that, by virtue of that blood flow increase, that increases, enhances cardiac efficiency.

38:02
So that's another, but there's a direct effect of ketones on the cardiac, on the cardiomyocytes, the actual like muscle fibers. So they are very efficient when they use ketones as an energy source. And the paper that you referenced that you're talking about actually looked at D-beta hydroxybutyrate and L-beta hydroxybutyrate, the two enantiomers. My wife has a product, I usually have it in my bag. I take it every day. It's Keto Start. So that product,

38:31
I believe it's maybe the only on the market that uses the D and the L. When you consume it, D gets burned up as fuel really quick, so that's an efficient fuel. And then the L hits all the signaling pathways associated with it, like the NLRP3 in flamazone, maybe some epigenetic effects. But then there's a racemase enzyme that also converts the L to D. So it's almost like a sustained... That enantiomers is like a sustained form of ketones.

39:00
where the L retains its signaling function, but because the metabolism is quite a bit slower and there's an inner conversion to the other enantiomer, not to get too technical here, it basically results in like a long tail if you do a pharmacokinetic study, if you like the Vash, like the D goes up and goes down because your body burns it up quick, it's a very fast burning fuel. And then the L kind of sticks around and there's like a shift, pharmacokinetic shift to the right, the curve.

39:29
So I think it's beneficial to have both of them. And what that paper showed that the L had distinct effects on cardiac efficiency that were favorable for cardiac function. And one could speculate that that would be the same perhaps in the brain or in the muscle too, but studies have not been done. Oh, that's super interesting. So your wife, Silla, is that correct? That's... Chilla, yeah. Chilla, Chilla, okay. Yeah, yeah. Chilla's product. Nervous science too from Semmelweis. So her background's from...

39:59
Yeah. I'm mostly focused on neuroscience. Yeah, nice one. And I've tried the tea and I've tried the coffee, love them both. And in fact, I have the tea with me here. I'm drinking the coffee here. Nice one. So Heroproduct's got both of them in them. What do the like, because I know there's obviously the Delta G as an ester, I believe, and there's also you've got the likes of Prove It and the ketone salts and stuff out there. What form of ketones do they provide?

40:28
on? Do you know? Like are they probably deep? Yeah, so we've researched all of them. Yeah, we're kind of, well, I'm kind of agnostic as to what to research. There are different ketones have different applications and one that has been very effective for the anti-seizure effects is called RS13-butanediol acetoacetate diester. Okay, so what that means is that

40:57
Butane diol molecule, the butane diol molecule is sold by HVMN as Keto IQ and it's sold by kinetics. And it's, so that's being marketed as a ketone ester, but it's really not. It's a glycol, essentially a di alcohol. So when we consume 1,3-butane diol, it goes to the liver and the liver needs to metabolize it to beta hydroxybutyrate. And that involves an alcohol dehydrogenase enzyme.

41:26
does make in the process of converting that precursor to ketones, it makes an beta hydroxybutyrate aldehyde. So that can be mildly toxic. And if you take a lot of it, my concern is that older people may be consuming a lot of 1,3-butanediol or 1,3-butanediol

41:47
based ketone esters, if they're older, it gives you a nice buzz. It has a mild narcotic effect. It was looked at as a space food by MIT back in 1975, and I have all the original documentation about that. And I actually researched it as a space food, but it had some issues. But nonetheless, it's a good ketogenic precursor. And we've used 1,3-butanediol for cancer, and actually shows it has some nice cancer suppression effects.

42:16
If you consume it before a run, it's not going to increase your exercise performance. I don't care what. So there's no studies. It's marketed as, yeah, yeah. All the time. Yeah. I see it all the time. Yeah. Interesting. You know, one exception to that could be in the context of things that we study, which is extreme environments. So if you were, for example, on top of Mount Everest, although the narcotic effect of the 1,3-butanediol could counteract that. Yeah. And that it's sold as like,

42:45
It's sold as hard ketones as an alcohol replacement, but it kind of is an alcohol too. It's better. It's better than ethanol. So I'll say that. Yeah. A little bit different kind of buzz, but so that's, that's the, the simple and cheapest, like actually in my refrigerator in our lab, we have like big, you know, gallons of the stuff and we use it, we use it to synthesize ketone esters and use it for, for some projects. So it's, it's good. Like, you know, it's been around forever. It's dirt cheap.

43:14
I mean, they're selling it, I don't know, like $5, but there's like five cents of actual like product. That's what 1-3-butanediol is like super dirt. It's like a industrial solvent, so it's super cheap. But you can make ketone esters out of it. You can make a monocluster beta hydroxybutyrate by doing a transesterification and adding beta hydroxybutyrate to it. Or what we did, we took 1-3-butanediol, did a transesterification and added two acetoacetates to it. So when you consume it,

43:41
you get a one to one ratio of the two different ketones. And for reasons we don't fully understand that keeping that redox ratio in the blood and in the brain has a profound anti-seizure effect. Yeah, interesting. Point where if we just jack up beta hydroxybutyrate with a 1,3-butanediol, there's no anti-seizure effect. Actually trending to like even like faster seizures, whereas the.

44:07
The diester is like a miracle anti-seizure drug. That's not a drug. And it brings down to, you know, our endogenous metabolites that we make anyway. So we have ongoing studies with that. And then my preference for me personally is the ketone electrolyte salts. So that would be back in 2011 and 12,

44:30
We realized sodium beta hydroxybutyrate was the only ketone on the market and it was the DL. And then it's like, okay, I want to give this to animals, but I don't want to mitigate the big sodium overload. So how do I do that? Oh, I could just mix it with some potassium. So I searched for potassium beta hydroxybutyrate and it didn't exist and I couldn't buy it. And it wasn't even in the CAS database, like the chemical data, like no one had made the molecule. So I reached out to...

44:56
chemist Patrick Arnold and it was like, yeah, it doesn't exist, but it's like, here's how to make it. It's super simple. So we made like sodium, potassium, calcium, and magnesium beta hydroxybutyrate. And we called that like the quad salt. And that's being sold like go BHB by someone patented that it's long story, but, uh, but we kind of conceived of that and then we made it and then we tested it and we spread the beta hydroxybutyrate across different electrolytes. Yeah.

45:23
The ideal electrolyte ratio is similar to the product element. Yes. Love it. The element is just the ketone or just the electrolytes. And then a product like Keto Star is the same electrolytes, but the ketones are bound to the electrolytes. Oh, that's nice. So when you consume that, it's giving you the electrolytes and the ketones. I think for like, a lot of people ask me, so that's essentially when that's like the ketones in its purest form. There's also the free acid form.

45:53
where you can get beta hydroxybutyrate in the free acid, and that would have to come in a liquid form. And I think there's some companies selling that too. The only thing, I've tested that thoroughly. That was like the first thing, that was the simplest thing that we tested, but we didn't have any therapy. It had no therapeutic effect, and it also created an acidosis. So the thing with the ketone electrolytes is that the electrolytes are good buffers. So they neutralize essentially the acidic load.

46:20
from the hydroxybutyrate is an acid and it needs to be in a relation and it burns your throat. I have like canker sores from drinking that stuff and I don't think it's good for the mucosa in your life. So ideally you want the beta hydroxybutyrate D and L enantiomers spread across electrolytes that you don't want to take like during exercise. So you get like two bags for your buck. You get electrolytes and ketones.

46:49
And then you get the D and the L and that has, we're doing a lot of research on that, showing that like early on we studied that and a lot of people jumped on the D beta hydroxybutyrate bandwagon because that was like more efficient. But then I kind of knew intuitively that they would come back. So now that a lot of marketers are going back to the L, like L enriched formulations, but I kind of knew what's were 2025. I knew 15 years ago.

47:17
Yeah, because we tested both and we kept seeing like the racemic is better than the pure D, but your body makes D, but it makes a little bit of the L with an enzyme called a racemase, but it trickles it. But if you give both together, then we're getting these interesting therapeutic effects, especially a lowering of the blood glucose, which in our lab, that's a very good thing. The hypoglycemic effect of the racemic is something that we

47:46
or cancer studies. Of course. And I'm thinking about like, I'm an endurance athlete. So run long and slow, that kind of thing. Like, is there a use case for, do we know yet if there's a use case for ketones in endurance sport, Dom? Yeah, yeah. Well, so we've published some papers on that. And a good person to interview for that would be Dr. Andrew Kuhnick. Yeah. So what I'll say for that is that...

48:15
When I entered the space, research was being done by DARPA on war fighter performance program, so making super soldiers. So the ketone esters were being used for that. And I saw the data for that. And it was always like a two or 3% increase, but these were elite athletes. So two or 3% was like pretty significant from like growers and things. But in reality, it just didn't.

48:43
pan out like this. Maybe like in a controlled setting, one could design the experiment to show that. But in the real world effects, I think you'd probably get like a bigger boost with a more of a dual fuel kind of scenario, like being low carb, low carb adapted, and then using ketones with a source of like a slower burning carbohydrates. And

49:11
I don't want to show all my cards here, but there's a lot of other metabolites that could also... My original interest was something called alpha-L-polylactate, which is lactate, but in a polymer, and that your body would trickle out the lactate. Someone listening to this will probably go file a patent on that. But yeah, I got interested in that for the brain, and I was like, oh, okay, there are some therapeutic effects, but then it didn't have anti-seizure effects, but the ketones had anti-seizure effects, so we jumped on that.

49:40
But I think for the athletes, in the context of extreme environments, in the context of being cognitively sleep deprivation, in the context of exhaustion, the ketones, if you kind of buy into the central governor theory... Yeah, which I do. Your brain is controlling your physiology and cardiorespiratory function and the neurons are sending the signals for the muscles to fire.

50:10
If we preserve and enhance brain energy metabolism, that then becomes the sort of the leverage point at which we can preserve and maintain exercise performance. So our work has been on, if you take like a normal healthy person, give them ketones, run them, there's no effect. But if you take someone that's extremely fatigued and you put them in extreme environment and you give them ketones, then there's like a benefit, you know, like the oxygen.

50:39
It's one of the things that, I mean, it was like almost too good to be true. And we did a number of studies. So just like real simple, if you give rats a high dose of ketones, elevate beta hydroxy to butyrate, and acetone, and acetate, and give them five atmospheres of oxygen, like they can withstand extreme levels of hyperoxy and use oxidative stress and just be grooming like normal where the other animals would like have a seizure until the point they would die.

51:08
These early observations really lit the fire under me to be like, okay, the brain is functioning more efficiently and metabolic physiology is enhanced in some way that's making this animal a rat, a super rat. I have to figure out the other applications. So it was like a niche application, but then our, one of our studies, it just spanned off into many different scenarios. So what I'm saying is that I think, uh, exogenous ketones are just one of the

51:37
for exercise performance, and they should be incorporated into a formula, especially if you're an extreme athlete. And I am talking about them in the context of acute administration, but I also think about exogenous ketones as a training aid. People use caffeine to run faster within, you know, take it in the morning to run faster during the day.

52:07
as a training aid, of course, they're illegal, like an Olympic competition. They're using it to augment the adaptive response or the recovery response to an exercise intervention. So that's how I think ketones should be used, although we have a paucity of data using them in its context. They administer ketones. They put them on a treadmill or bike and be like, OK, no effect. Ketones don't work.

52:32
So, but in the context of extreme environment, they do work in different experimental design. So, there's different trials on that. But they really need to be tested in the context of, you know, being used as a training aid. I think that we'll see the most benefit from the anti-inflammatory effects, the recovery effects, the brain health effects.

52:55
Yeah, I work with a company, S-Fuels, and they include ketones in their recovery shake, actually, like eight grams, I think, of beta And I'm not sure how they actually formulated the fact that it's, I think it's eight grams. And I actually tried Delta G, I think, during a run, like it was a long, maybe five-hour run or something. And in fact, I'm like, I'm just going to take the whole bottle, which was actually a terrible idea because I felt immediately hypoglycemic after I did that.

53:24
taking short, smaller amounts across a specific time period is probably better. I knew you were going to say that before you even said it. I can explain the physiology behind that too. Yeah, you can do it. There's a way to use it to avoid that. But yeah, so yeah, if I'm at my desk and I'm in a fasted state or I'm exercising and I drink Delta G, at the time that might have been the monoester or the diet. So yeah.

53:49
What generally happens is a pretty quick rise of beta The counter-regulatory mechanism that helps us maintain new ketonemia is basically we get into ketosis, the ketones get elevated, we have ketone urea that helps moderate levels, but there's also a ketone-induced increase in insulin from the pancreas. So that feeds back and turns the dial back, doesn't shut off, but like a rheostat, if you want to think of that, it shuts down.

54:17
beta oxidation of the fatty acids in the liver, that's actually part of the ketogenesis process. So our ketones get elevated, the liver pulses some insulin, fatty acid oxidation, the liver goes down. So that regulates our ketones. When you take a big dose of a ketone ester, and that's why I favor the electrolytes, even for athletes, it spikes ketones up, you release insulin and that causes glucose uptake.

54:47
you have a corresponding hypoglycemia, but you have the hypoglycemia at the very time that you're hypoketotic. So you take it, you have ketones for fuel, you have glucose, but then your glucose drops and then you burn off the ketones. So as the glucose drops, so this is like put people in the hospital and stuff that they're like, what happened? I was like, okay, here's what happened. So actually I've been kind of talking about that a little bit.

55:12
There's ways to avoid that. Like if you take a slow burning carb, like you just need to experiment. Yeah. And you could get around that the whole ketone induced insulin response by something about the ketones with electrolytes. I think it delays gas absorption in a way that I've taken a double dose of Keto start and then did an insulin test 30 and 60 minutes later. Yeah. And there's no effect on insulin even though my ketones get elevated, you know, up to the

55:42
in that scenario. I think the Chilis Keto Coffee would actually be great fuel. So you've got that sort of continuous, you've got caffeine coming in, plus you've got the electrolyte salts, the salts and the ketones. It actually sounds like a really good use case for that product.

56:04
Her coffee product is a Colombian instant coffee that's low in caffeine, but I actually use it as a keto spike. So I will brew coffee, I have my coffee, it will coffee snob. So I'll brew like a certain brew coffee, and then I add a packet to my coffee to spike it with ketones. So I have, you know, it's a little bit stronger coffee, but I have like my brew coffee, and then I literally, the product is called keto spike. I spike it with the ketones. So I have the caffeine from it. Because some people,

56:34
Yeah, caffeine is like a kind of a tricky thing. Some people are trying to back off on their like if they're already drinking coffee, and they like, you know, instant coffee can have a lot of caffeine. So we debated I was like, we'll just find a really, really high quality coffee, and then try to play that with the ketones that doesn't have the caffeine in it. And I was like, because I want to use it too. But I like coffee. I like brewed coffee, but I like to, you know, just jump, you know, spike it up with ketones.

57:02
Yeah, yeah, nice. That's actually a great idea. I'm going to look into that because I've got the stage race coming up at six days of running between like 40 to 70 kilometers a day. And I'm going to need something particularly in days four, five and six of that event. This morning, Mark Bell, he's got like a big podcast sent me, he just bought over $500 of keto spikes. So he's been, he's a big runner. He just transitioned. He was a huge power lifter. Yes.

57:30
how he's running and basically is just being fueled off the keto spike coffee and just bought like a ton of it and showed me the screenshot of what he bought. I was like, Hey, that's what I'm drinking now. On my way to work, he had sent that today. So actually, that's amazing. I did actually hear Mark talk about how he was also on the side of a road with a similar experience to what I just described with when I took a whole thing. And I listened to that after that happened to me. And I'm like, okay, so this is not a same experience.

57:59
I know other people that have been hospitalized by that experience. So ketones are very powerful. So you have to respect them and use forces that are not going to have that counter regulatory effect because you don't want to really spike your insulin. You want to keep that fat flow going and spiking insulin will prevent that. But ketone electrolytes just seems to augment fat metabolism in a way. And you could also mix.

58:25
ketone electrolytes with like an MCT and that keeps the liver wrapped up too for fat oxidation. Yeah, nice one. Dom, I'm aware that we didn't even get on to talking about that study which I just wanted to chat about and you've got like a hard stop in about 10 or so minutes but can we just sort of circle back and just finish off with this study because I thought it was sort of interesting because they were comparing just a free sugar

58:54
free diet, and I'll get you just to sort of chat about what that is, versus a, I think it was ketogenic diet, 60% of the calories coming from fat over a 12 week period. So it was quite a long period. Yeah, yeah. So the take home message really was like, you know, and we did a whole journal club deep dive on this, I think, was that, you know, sugar free or low sugar is a pretty

59:24
weight loss, shoulder restriction has the biggest impact at least short term. And the transition to a ketogenic diet cause in their, the way they wrote it up, like alarming changes in an atherogenic markers in the blood. So you do need to get like a four to six week transition period. And during that four to six week transition period,

59:54
you're going to get some pretty funky, like a lot of variability and different blood markers in your lipid panels for some people. But athletes tend to be a little bit less, you know, a little bit more resilient to those changes because they're already burning fat for fuel. So, you know, what's happening is that, well, there's a lot of things happening. So maybe if you have any specific questions, I think you

01:00:23
sent them to me, but you had questions about the keto diet. Yeah, I did. So, you know, they, I mean, you mentioned that there are transient changes that occur in the blood because of the diet change, which was the focus actually of the take homes from the paper. They focused on these four week changes, despite the fact that it was a 12 week sort of intervention. And I just was interested to sort of talk about

01:00:50
those things like the potential for the reduced glucose tolerance that they also discussed and the increased ApoB levels seen and so what the mechanisms were for that. Yeah, so when you follow ketogenic diet, what happens is that insulin goes lower and glycolytic flux, so that the flux of glucose metabolism is decreased. And then...

01:01:13
It's stimulating fatty acid oxidation. So the use of fat for fuel. And then if that's maintained, there's a lot of adaptive changes that happen with that. Even like, I mean, at the simplest level, like a decreasing glycolytic enzymes, like hexapkines, and then like an internalization of the glucose transporter. It's like not at the level, it's not like on the surface of the membrane, it gets internalized because there's less glucose. It doesn't need it.

01:01:38
So these are, yeah, and if you reintroduce carbohydrates or glucose, there's a bit of glucose intolerance and even anyone who's like been on like, you know, a low carb diet and then goes out for pizza and eats like tons of carbs, they get bloated, like they can't even, you know, absorb it into the gut. They have like gut problems, they have, you know, they blow up because they have hyper insulin response and that increases water and sodium retention. It's a metabolic mess.

01:02:05
So that's kind of what's happening. So that's like a normal physiological response. You can reverse that. And ideally, like if you're coming off a ketogenic diet, wanna titrate the carbohydrates back in over about two weeks, like two to four weeks if you've been on it at the same time. So the high APO-B, if you...

01:02:24
gravitate towards eating a low carb diet and you have high fat oxidation, the triglycerides and the phospholipids need to be transported for fat and for the use of fuel, right? So fat is transported by lipoproteins and ApoB is a component of the lipoprotein that is involved in fat transport and phospholipid transport. So you need to have proportionally more ApoB, we think.

01:02:53
So, and there's also like, you know, changes in like the LDL receptor and some other things going on. But I think generally speaking, the science is like going towards this consensus that if you're eating more fat and you have much more fat fatty acid oxidation at the level of the skeletal muscle, you need to transport that fat and how you transport the triglycerides and phospholipids. You transport it, you know, with, with lipoproteins.

01:03:19
So I think a light book, and that's more prominent in people that are lean and more athletic. However, if you have people that have metabolic syndrome that are overweight, type two diabetes to begin with, their AboB and LDL often come down when they follow a ketogenic diet. So that's like pretty common. But in regards to athletes and lean, that's why they call it lean mass hyper responder because the observation is that people with lower BMI tend to trend.

01:03:48
in the direction of this elevated APOB LDL and APOB with sustained ketogenic adherence. And do we think that in that context, in the lean mass hyper responder, which I would love to talk Dave Feldman much more about, but also just in terms of like your lean athlete following a ketogenic diet, these increases in these markers that we think are atherogenic are actually not

01:04:18
we sort of think. That's an ongoing area of very active research, largely spearheaded by Dave and a few other high level academics, cardiologists are looking into that. And I think we've demonized LDL. We've sort of glorified statins as these tools that can save our lives by pushing LDL down into like single digits.

01:04:43
Well, I mean, it's important to acknowledge that, you know, it's very context dependent. So if there's acute effects and then there's long term effects of dyslipidemia, elevated LDL, but if your triglycerides come down and they stay low and HDL goes up ideally and HSCRP goes down over time and they pop up in the beginning because ketogenic transition can stimulate a little bit of oxidative stress, especially in the liver in the beginning. But a lot of people, it comes down.

01:05:13
And, you know, hemoglobin A1C and glycemia are improved. These are just like, you know, just standard things that happen on low-carb ketogenic approaches. It needs to be viewed in context. So you also need to consider, like, have you had a heart attack? Are you at atherogenic risk? You know, family history and your genetics too. I mean, I have a rare mutation in a receptor, the Neiman pick.

01:05:41
like C-like one receptor, the MPC1L1 receptor. So that's involved in cholesterol absorption. And if you have a mutation, presumably, I have a gain of function where basically I suck up lots of cholesterol from, and even at the level, like in the gut and also it's thought in the liver. So what I have done personally, no medical advice, but I have kind of higher ApoB and everything improved and really high, and I just microdose azetamide.

01:06:10
not statins, azetamide just basically kind of blocks, you know, the function of that transporter to a certain degree. And I'm just doing like a half of a tablet every other day. And then it takes my APO-B from 125 down to like 60 or something like that or 50. So it like literally cuts it in half. And there was also the added benefit of it popped up my HDL a little bit and my triglycerides went down a little bit. So, and I don't...

01:06:38
have any side effects at that dose. However, if I take like the full dose of the Zetamide, my liver enzymes trend up a little bit higher and I don't like, if I like microdose it essentially, getting some benefits from the APO-B. So this is a little experiment that I'm doing because you know, I don't know. I think we don't, I would like to now like everything is like great, right? So I have improved.

01:07:05
Cardio lipid, cardiometabolic profile, even my blood pressure is great, but I have this like LDL and APOB and my LP little a is a bit high too. So that was motivating me to at least bring my APOB down or just reduce it down into not an astronomical range. Yeah. So there was any comp, I would not compromise on energy performance. Like, you know, if it had any side effects, it was like a no-go for me, but actually, I don't know. I actually.

01:07:34
I've been taking a low dose and felt really good. Yeah, that's great. You were taking psyllium husk or using psyllium husk for a time. Did that make an appreciable difference to anything for you, Don? It did a little bit, like maybe 10 to 15%. But I don't like to have like a lot of bowel movements throughout. So psyllium husk is, it's for me, like I'm so regular, but I don't want to be hyper regular, right? Yeah.

01:08:01
schedule. Plus, at nighttime is when I kind of get most of my fiber. I basically have like protein, fat, and polyphenols of, you know, cocoa and coffee and stuff during the day. And in the evening, if I have fiber in the morning, then I get a little bit bloated throughout the day. So I tend to get my fiber later in the day. And that's wild blueberries, walnuts, and an apple. I have like these little like kind of like wild apple kind of thing.

01:08:29
So there's a little bit of tart and that's what I have pretty much every day. And I might add a little bit of fiber here and there. But generally speaking, like if I'm traveling and I don't have access to like those kinds of fruit, I'll include the psyllium, but it's pretty effective. So it is. And a lot of people have, some people have constipation issues and that'll solve. Solve them, yeah, for sure.

01:08:52
Can we very quickly just finish off with some of the gut microbiome? Is it just your opinion on the gut microbiome argument around ketogenic diet? I even heard it on another podcast in the last week that ketogenic diet is terrible for gut microbiome. I guess I just want to hear what your response is when you hear something like that, which was...

01:09:14
I'll include the paper, even though we're very briefly touching on some elements of it, but I'll include it in the show notes for people who are interested. But this was another thing that came up in that paper. Yeah, well, there's a lot of ambiguity and kind of a lot of things we don't know about the gut microbiome. But I will also say that there are different types of ketogenic diets. So the ketogenic diet that I follow is very rich and has kind of like the recommended amount of fiber.

01:09:43
which a lot of ketogenic diets don't. So, bifidobacteria, I think, was identified as being low. So that was like the red flag in that study. So, bifidobacteria feeds specifically on carbohydrates. So if you reduce the amount of carbohydrates you're eating, your bifidobacteria will naturally be less. You know, bifidobacteria...

01:10:07
has a lot of positive things going for it. It does increase short chain fatty acid production. So one way to simply do that is to just kind of like, I don't know, do what I do. I get soluble fiber throughout the day, typically at the end of the day. Psyllium husk is a great source of soluble fiber that has been shown to increase bifidobacteria. So you could just...

01:10:35
You know, my approach is just like protein, fat, ketones, and polyphenols throughout the day. And polyphenols have a favorable effect on the gut microbiome. I'm actually writing a review about that. It's like a really nice effect. So think cocoa, think coffee, cocoa, tea, blueberries, nuts, things like that. And so there's that, but also fish oil, you know, soluble fiber, maybe berberine too.

01:11:03
When you go on a ketogenic diet, you do have a lot of pretty profound changes in your gut microbiome. One thing to do is maybe do it slow. If you don't have like a seizure disorder, epilepsy, you don't need to jump on it like immediately, that transition helps to avoid side effects and helps people adhere. We had to do that for one of the studies. We had a really good adherence if we transitioned them over four weeks. Oh, nice one. And I guess there's just so much we don't know about the gut, right? And if...

01:11:32
everything else improves and you've got no noticeable gut issue, then who's to say that that's not a healthy diet for you? Oh, and I forgot to mention that in the world of epilepsy research, the ketogenic diet's mechanism has been thought to be perhaps an elevation of acrimencia. So acrimencia is a...

01:11:56
part of our microbiome and it plays an intimate role, like a really important role in increasing mucus production, that mucus barrier function. So acrimentsia is like, if we wipe it out, then that really compromises the barrier function and we get essentially leaky gut and compromised intestinal permeability, and then that could lead to inflammation and other things. So the ketogenic diet, several groups

01:12:24
have reached out to me and they're convinced that it's not the ketones. Well, the ketones could be part of it, but they're convinced that the key to the effect of the ketogenic diet, at least on animal models, has to do with expanding the acrimencia population. So so that's you know, there's in regards to diversity and the bacteria, I'll agree that a strict ketogenic diet that maybe is deficient in protein can lead to those microbiome changes. But then.

01:12:52
That's why you want a ketogenic diet that's, you know, high in prebiotic fiber. And if you're, you know, for different reasons on antibiotics or something like that, you might want to use a probiotic, but I'm only in favor of using a probiotic in certain circumstances. Like if you're recovering from a gut bug or taking your... Yeah. Dom, you are a wealth of information and we, you know...

01:13:17
went off on some really interesting tangents, which I think people will really enjoy hearing us talk about. Can you let people know where they can find more from your lab and of course, just what you do personally. You're very good at sharing on Instagram. Yeah, thanks for asking. Yeah, I have, we can find, I encourage people to go to the website, keto and then,

01:13:40
go to the metabolic summit.com part of the also the metabolic initiative where we have a lot of content on there, including the metabolic link podcasts, which we break down many of these topics. That and yeah, I mean, I'm pretty much active doing research. I teach full time. I do research full time and any free time I have. I'm very passionate about education outreach. So I want to thank you for giving me this platform to talk about. You know,

01:14:09
these different aspects, you know, important aspects we talk because equally as important as publishing papers and doing science is maybe more important is getting the science, you know, to human application. So moving the science to application is kind of like our motto, right? And you're doing that by spreading information and getting this, this work out there and people can take more of a deep dive if they're interested in these topics. Yeah. Awesome, Dom. And you, and all of the ways that people can reach you, like you're so

01:14:39
You provide so much of that practical application information for people, which is amazing. Thank you so much for your time. I really appreciate it. Thanks for having me.

01:15:02
Alrighty, hopefully you really enjoyed that and apologies if you found some of the audio just a little bit challenging. We did have some challenges with the file, but hopefully the conversation itself was enough to keep you hooked and engaged. Next week on the podcast...

01:15:17
I'm stoked to bring you the conversation that I have with Tony Boutagy. And we discuss strength training, we discuss carbs and performance. And I've had Tony on the show before as well. And this is really like a nice follow up conversation based on that and on Paul Lawson's interview that I also published a few weeks ago now.

01:15:42
Just to remind you that the doors for Monday's Matter are open until Sunday, week of cough, Monday 10th of Feb. Join me for my eight week fat loss program. I am running it now and running it again in September. There will be no May intake. So if you were looking to sort of try it out and weren't quite sure when to do it, sign up now because it's not back for a while. There are links to that in the show notes as well. Or hit me up.

01:16:09
in the DMs over on Instagram @mikkiwilliden and that's the handle to also find me on threads and Twitter and then Facebook @mikkiwillidenNutrition or head to my website, mikkiwilliden.com. All right team, you had the best week. See you later.