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episode #193

Friendly Debate with Dr. Dom D’Agostino and Jay Feldman: Low Carb vs. High Carb – Part One Hide Det

October 20, 2022 in Podcast


This week I interviewed Neuroscientist, Keto Researcher and Professor - Dr. Dom D'Agostino and health coach and researcher Jay Feldman!

This was a friendly debate discussing a myriad of topics such as:
  • What is the Preferred Fuel Source for the Brain
  • Is the Clinical Keto Diet Healthy in the Long Term
  • Glucose Oxidation vs. Fat Oxidation
  • The Importance of Gut Health
and which foods to remove that could be toxic to your health, plus more!

Connect with Dr. Dom D'Agostino and Jay Feldman:



Brian (0s):

Coming up on the Get Lean EAN podcast,

Jay (3s):

We should see when we shift from a moderate or high carbohydrate diet to a zero carb diet, we should see increases in glucogon adrenaline cortisol. We should, I would say, feel a stress effect from that. I think that that's the normal shift from glucose to fat oxidation, and then glucogenesis and ketogenesis, those are the normal hormonal regulators of that state. And so I think we should feel that difference. I don't know if it should necessarily feel good or if we, if it would be a good idea to not have any effect there. And I think this is why a lot of people might want to use exogenous keytones to help shift that faster. So that,

Dom (34s):

So I'm gonna interject there. So, so the stress response, I actually agree with, like when you go on a ketogenic diet, there's an elevation of cortisol, catacholamines and glucagon. But I believe my, my view is that that's a beneficial thing that helps facilitate greater fat adaptation. And then those things, I mean, according to our data and most published data is that these things just come back with a u caloric diet will just come back, back to normal. It's much like, you know, if I get under the bar and squat 500 or whatever, that's a stress and it releases all sorts of crazy things, right?

Dom (1m 15s):

But from my contacts, it's from my contact. It's the adaptation to that stress that is most important. And I think some people definitely communicating with them, they absolutely fail to adapt to a ketogenic diet. And they do it and they're actually losing weight, but their triglycerides go up and, and their, you know, LDL goes up and their blood glucose does not go down. And for reasons I don't really know, maybe they have some snips. They're just, they're just not good fat oxidizers. And most importantly, they don't, they don't feel good. They have a lack of energy. But if you go on a ketogenic diet and you sustain it, the benchmark is, if you have lots of energy, if you're on a ketogenic diet and you're burning fat and keytones instead of glucose primarily, and you feel great and all your metabolic markers are great, then it would be hard to argue that that's bio energetically unfavorable if you have energy.

Dom (2m 11s):

So how could it be bio energetically unfavorable if the person has tons of energy and all the biomarkers are good?

Brian (2m 19s):

Hello and welcome to the Get Lean E Clean podcast. I'm Brian Grn and I'm here to give you actionable tips to get your body back to what it once was, five, 10, even 15 years ago. Each week, I'll give you an in-depth interview with a health expert from around the world to cut through the fluff and get you long-term sustainable results. This week I interviewed neuroscientists, keto researcher and professor Dr. Dino and health coach and researcher Jay Feldman. This was a friendly debate discussing a myriad of topic such as, what is the preferred fuel source for the brain? Is the clinical keto diet healthy in the long term? Glucose oxidation versus fat oxidation, The importance of gut health and which foods to remove that could be toxic to your health.

Brian (3m 6s):

This was a great friendly debate between Jay Feldman for the Biogens Field, along with Domino, who's been a long term proponent of the keto diet. And I've been trying to get this on the books for a while, so I'm really excited to send this out to you. It's longer than most of my other interviews, and when, about two hours. So definitely sit back and relax and enjoy. You could watch part of it one time, part of it the other time, either way, there was a mini earthquake in the middle. So I hope you really enjoy this friendly debate. You gotta sort of a low carb versus a high carb approach, and this is part one. So enjoy my friendly debate and interview with both Don and Jay and have a great day.

Brian (3m 47s):

Thanks so much for listening. All right. Welcome to the Get Lean e Clean podcast. My name is Brian Grin and I have two great guests on for a nice friendly debate. Jay Feldman and Dr. Don de welcome to the show.

Dom (4m 2s):

Thank you. Thanks for having me on again. Yeah,

Brian (4m 4s):

Yeah, we found out they're both, they both lived in Tampa for a while, so maybe they crossed each other's paths at one point, but here we, here we go. And I'm glad to have you both on, We're gonna talk about a bunch of discuss discussion points that I've mentioned earlier to both of them, but I thought it would be good. Before we get into that, I have had Dom on before, but Don, maybe you'd lead us off and just give us a little bit of background of yourself and then Jay you can follow up.

Dom (4m 31s):

Sure. Well, I've always been interested in nutrition ever since I was in high school, I think. And you know, for sports, for football and things like that. Majored in nutrition and biology biologist an undergrad, and that led to a PhD in physiology and neuroscience at Rutgers University. And then I did my postdoc that was funded by the Department of Defense and Office of Navy Research. And it was at work that led me to the ketogenic diet because most of what I study in the context of nutrition or dietary interventions is for seizure control or neuroprotection. And we also do some cancer research and, and I moved to Tampa in 2006 as a postdoc and worked my way up to tenure professor.

Dom (5m 18s):

Now I teach neuropharmacology physiology, neuroscience, and also teach nutrition to the medical students and mostly, and I, and I work in some of the ketogenic stuff, so I have an appreciation for, you know, conventional nutrition guidelines, but also an appreciation for a low carb approach under certain situations.

Brian (5m 42s):

Awesome. And Jay?

Jay (5m 44s):

Yeah, so, you know, starting off with a very similar path, you know, very interested, very much interested in nutrition from a young age for a lot of fitness driven inspiration. And that then led to in school, I was, I was pre-med and wanted to go that route. And as I learned more at the time, a lot about low carb fasting, things like that, got very involved with all of those and, and felt like the conventional medical approach was not the route to go. And so I finished my studies in exercise physiology and neuroscience and went on to do some independent research where I spend a lot of time reading studies and writing paper or writing articles and, and also health coaching.

Jay (6m 27s):

So I work with people one on one and have shifted my perspective from a more low carb, intermittent fasting type approach to one that more or less includes the opposite, which I'm sure we'll be talking about today.

Brian (6m 40s):

Sounds great. And yeah, I, I first learned about Jay through Brad Kerns. He was on the Be Rad podcast and, and Dom has been on a lot of different podcasts and I've known about him for a while. And he was a current guest a while back, I don't know, maybe six months ago, give or take. So I thought it'd be great to have you both on, and perhaps we can start off right off the bat with, you know, touching on advantages of like low carb versus high carb, but I think this is like a common debate that goes on in many different circles. Maybe Jay, why don't you start us off and, you know, I know you mentioned you, you started off, you know, doing fasting and low carbon, things like that and sort of led you down another path with like the Biogen path.

Brian (7m 27s):

Maybe explain how that, how that came about.

Jay (7m 31s):

Sure. Yeah. So I had been, you know, in that space for a while, several years and did various iterations there, including ketogenic diets and cyclical ketogenic diets. And over time, personally was not experiencing a lot of what I felt like were the health benefits that were promised. And so that led to situation where I was open to considering other possibilities. And when I came across some information that had kind of opened my eyes to the idea that maybe carbohydrates weren't the devil that, you know, I had taken them in to be, I started to shift my approach and it led to a lot of shifts in how I felt in terms of energy performance at the gym, adaptation to what I was doing at the gym, as well as libido and, and on and on there, focus, things like that.

Jay (8m 17s):

And so, and, and that kind of shift came as you mentioned, Brian, from exposure to what's called the bio-energetic view of health, which is the idea that the energy that's produced, you know, within the mitochondria of every cell is the currency that drives health and function and a lack of which drives degeneration. And so that shifted my perspective in terms of how I was doing physiology and yeah, led to, among other things, the inclusion of higher amounts of carbohydrates.

Brian (8m 50s):

Excellent. Okay. And, and do, I know you've obviously been involved with like the keto died and the applications regarding that. What, what are some of some of the applications that you've found beneficial for the keto died?

Dom (9m 3s):

Yeah. Well my, the first application really is I've been involved in the world of epilepsy and chair, the American Epilepsy Society Special Interest Group in dietary therapy. So that has been kind of like the thing that got me going, but, so there are various operational situations where you, that make you more susceptible to having a seizure. And I was funded to study something that was kind of esoteric, which is a breathing high oxygen at a high partial pressure or a high bear metric pressure, which is using a closed circuit rebreather as the Navy seals do.

Dom (9m 49s):

And they dive and they, they risk CNS oxygen toxicity, which limits their operational activities. And also hyperbaric oxygen therapy has 14 different FDA approved applications. The limitation is seizures. So I started studying various model systems from mitochondria to cells to animal models, rats and mice, and then to humans and then, and then myself. I became a subject and lived underwater for a while in ketosis. So I've been studying it mostly from the context of preventing a seizure and but also in the context of rare neurological diseases that are pathophysiologically linked to impaired brain energy metabolism from, for example, a deficiency in the glut one transporter at the Blood Brain barrier Alzheimer's disease, which a project that we had like more than 10 years ago.

Dom (10m 50s):

And we can kind of talk about the bioenergetic effects of keytones in the brain, but my very early studies were actually measuring super oxide anion in hippocampal slices and in neurons, reactive oxygen species within without keytones. And I noticed that oxidative stress went down and this was like a clue that the keytones were impacting energy levels in the brain and that when the brain cells were deriving energy from Keytones, they were producing less super oxide, which is a precursor to more reactive species.

Dom (11m 29s):

And then that got me, this is like 2009 now. Got me very interested mechanistically in how keytones work. So I connected with many of the icons in the field. Some of them have left, left us, Dr. Richard Veach, he was trained by S crib. He developed some of the first KEYone esters, George Cahill, who did the seminal work in fasting at Harvard. But then I went down, you know, studying various genetic disorders, cancer, glycogen, sythes disorders, and a variety of different things. We have like a pop projects in the, in the, in the field. And now we actually do some human clinical trials on, for example, using continuous glucose monitoring.

Dom (12m 15s):

I got a CGM on me and we have patient data that we're working with and also studying athletes that are using high carb, low fat and low-carb, low-carb, high fat. So, and just got some data from from that now and could probably mention a little bit. But yeah, we're preparing, preparing the manuscript for pretty, pretty good high impact journal. So, and kind of embargo, but I'll, I'll mention some of the insights from that study cuz I think it could apply to the conversation.

Brian (12m 51s):

Excellent. And yeah, we'll, we'll definitely love to learn about that. And I guess the, the, the question is, is you know, what, what fuel does the brain prefer? And maybe Jay, what's your thoughts on that?

Jay (13m 9s):

Yeah, so preference I think is relative, obviously one keytones are available, the brain's going to use, you know, up to maybe 60 to 70% keytones and then the rest will be mostly glucose. So yeah, when keytones are available, I think those are going to be used more so than glucose. When keytones are not available, glucose will be used. One thing that largely cannot be used except for in very tiny amounts is fats. And I think that is an important thing to discuss at some point as far as the fat oxidation and potential issues there. I, you know, maybe it's worth mentioning now I have much less of an issue with keytones themselves or using exogenous keytones as much as I do from the health standpoint.

Jay (13m 49s):

And I'm sure we'll discuss the context with the ketogenic diet itself and what is involved in getting to that point where we are producing those keytones, endogenously

Brian (14m 0s):

And, and dam, what are your Yeah. Thoughts around that? Yeah,

Dom (14m 4s):

Yeah, I think, I mean, under almost all circumstances the brain is using glucose as the primary energy source. Only in the context of fasting would we transition. And it's not like glucose to keytones like you, like a lot of people talk about, it's a gradual transition as KEYone levels get elevated in the blood, they freely cross the blood brain barrier and are used as an alternative energy source, but only in the context of fairly extreme situations. So that would be, you know, limited food availability I guess, which was not, it was pretty common. You know, our ancestors limited carbohydrate availability, which maybe some could argue not depending if you're like the ZA or pre or post agriculture, you know, Japanese societies, you know, a lot of carbohydrate based nutrition.

Dom (14m 59s):

But as we age, the capacity for our brains to use glucose decreases with time. And that's not the situation with keytones. And we can get into that. And, and for certain things that we study, like even traumatic brain injury, there's like inflammation that could decrease the activity of an enzyme in Piru batease complex, for example, which is a hallmark characteristic of Alzheimer's too. And other age-related cognitive disorders, things like we look at like the Glu three transporter, which tends to be internalized when you have amyloid pathology. So these things would impair brain energy metabolism and in ways where elevating keytones in the blood through the diet, through fasting, that's a little bit tricky, but time-restricted feeding or supplement could have benefits in that.

Dom (15m 54s):

But from a broad context, yeah, glucose and or certain situations, keytones fats in the form of short chain fatty acids and MCTs do cross the blood brain barrier. So they could be used as fuel and lactate and, and small amounts of immuno acids could also be used. But kind of like in that order, you know, it's really glucose or keytones. And then in some situations lactate when you're exercising may contribute to, actually my first interest in brain energy metabolism was using lactate and delivering lactate with alpha poly lactate in the context of hypoxia or ischemia.

Dom (16m 35s):

And these are some of the first experiments that I was interested in doing in a hippo brain preparation in and I, and then something, yeah, I, I just into keytones,

Brian (16m 52s):

One of the questions would be sustainability of like a low carb diet. And I think that Jay has points, and I've read a lot of his blog and listened to his, his website, that these, when you are in a state of low carb are fasting, you know, you're releasing these stress hormones and you're running on glucagon and adrenaline and growth hormone and cortisol. Perhaps Jay maybe explain a little bit about your thoughts regarding that.

Jay (17m 20s):

Yeah, so as Dr. Dino had mentioned, the situations where we're producing ketones involve either entirely, you know, food restriction, if we're in, you could call fasting or long term it would be starvation or if we're fully deprived of, of glucose or any carbohydrate source. And so when, and I guess you could say also the kind of intermediate step, there is a shift largely from glucose oxidation toward fat oxidation. And then you get the ketogenesis generally following that. And so that shift in that direction tends to happen. Anytime we enter stress, we start to shift toward largely fat oxidation. And as you were saying, Brian, that tends to be largely mediated by, among other things, hormones, so largely glucagon.

Jay (18m 4s):

And then depending on how intense the stress is, we end up with adrenaline or epinephrine growth hormone and cortisol. And so the, this immediate stress date relies largely on fat oxidation. And then again, if it's continued long enough wind up with keone production. Now when we think of this, I guess you could say biologically or evolutionarily, one of the, you know, thinking of it in that big picture, one of my concerns are is that these are states of, of prolonged stress and lack of food availability. And with that tend to be states where our bodies would wanna depress their metabolism. And so the, and we see those effects not only in terms of the bioenergetic effects of largely relying on fat oxidation for energy production, but also in the hormonal effects.

Jay (18m 50s):

So normally in the, in that initial shift, you'll see largely glucagon but also a large amount of epinephrine and, and cortisol involves there. But over time you'll see less of the cortisol and epinephrine other than the acute instances and largely more glucagon. But that shift and those hormones tend to do a few things that will suppress the metabolic rate, one of which is decreasing the conversion from the inactive to active thyroid hormone. So they'll decrease the conversion from T4 to T3 largely at the liver. And less so glucagon, but especially more so the cata means. And, and cortisol will end up depressing various other kind of pro metabolic hormones. Hormones that stimulate the metabolic rate, including, including androgens, especially for men.

Jay (19m 32s):

So decreasing testosterone production and then also, you know, see parallel effects in women largely from progesterone. And of course when we think of this biologically, it would make sense that we don't wanna be prioritizing reproductive function or a high metabolic rate when we're in a starvation state, when we're in chronic stress. Cuz if we did, we would be using a lot of fuel that we didn't have at the time and put ourselves in a compromised position where we would die sooner if we're in this intense stress if we're under starvation. And so we can kind of break apart each other's pieces or talk through those differences and glucose versus fat oxidation and those cause that's really where the signaling starts. But either way then, my kind of largest concern here is that that state is not one that's conducive to health.

Jay (20m 15s):

And so it's not one that we wanna be replicating if we don't need to, if we're not actually starving.

Brian (20m 22s):

Thanks Jay. Dom, do you have anything

Dom (20m 25s):

To Yeah, I, I, I definitely have a share similar opinions in some areas, but we have a lot of data, Well maybe I'll start off by saying that in the world of epilepsy and I have different books, like this book was one of the first books I got by the late John Freeman who is Dr. Eric Ossoff's mentor. You know, and I tend to agree with the information in the books on epilepsy is that the ketogenic diet is not natural and it's not a healthy diet to follow. So it says that like, I think in the first, you know, in the opening line and that that's how it's viewed in the world of ketogenic diet and metabolic therapy.

Dom (21m 8s):

So when I started studying it, like in 2008, and I remember being on a podium I think in 2009 and mentioning that I was gonna ketogenic diet, I think the audience thought maybe I had seizure disorder or something, something, but I was doing it just much like, you know, I was doing it because I was researching it, you know, and, and I wanted to understand what a true like four to one ketogenic diet was. But I do agree with, with Jay in that a ketogenic diet is not natural. It's probably not optimal for, for health especially long term, but I continue to follow it and just kind of like, you know, like living underwater for 10 days.

Dom (21m 50s):

Not natural, but I kind of like, I did it for research purposes much as like, but I've transitioned away from a clinical ketogenic diet and I, I kind of agree with my wife in that I believe in flexible dieting and that eat what you love to eat, eat the foods that you enjoy unless it's causing a problem, right? And my wife eats Ben and Jerry's every night and you know, she's very good with, I'm not good with, with portion control. She takes out the the pint and has a little bit and puts it back and, and for me, you put a pint in front of me, I'm gonna eat the whole pint. So, and you know, she does very well on a, on a carbohydrate based diet, a higher car diet and she can back it up with blood work.

Dom (22m 37s):

Like her insulin I think was 3.3. Hemoglobin A1C is like 4.2. If you compared it, a doctor would probably say her blood work is superior. So maybe, you know, I mean a, a high carb diet is working. So I believe that any diet that the thing that should dictate the optimal diet for the person is atric, you know, body composition probably first and foremost. And then a whole range of blood biomarkers that we're measuring in the lab. So I don't, so where I disagree I think is that, and this is, we have a lot of data we're sitting on now, some of it we've published right now we're writing it up.

Dom (23m 18s):

We have athletes and then we have non-diabetic people who just, were part of our, our clinical trial, registered clinical trial who did a ketogenic very low carb intervention for 12 weeks. So I would say, I'm looking at the data now cuz I just got back, we're working with a statistician, a prolonged ketogenic diet if you wanna call 12 weeks prolonged, actually they had, they had normal amylin. So with normal amylin, the amylin induced glucagon suppression was normal. So, you know, that would may go against what Jay is talking about.

Dom (23m 58s):

We had normal in fluency, peptide glucagon was normal, GLP one was normal. There were trends that were actually, the glucagon was slightly lower from. So that, that was a little bit surprising. And then we also expected in hope that insulin would drop, but it was, we didn't see a statistically significant, we saw trends in decrease in insulin, but leptin dropped. So you would expect leptin to dropped grin increased, which we were hoping that grin would decrease that our hypothesis was that keytones and a car, carbohydrate restricted diet higher and protein in fat would decrease grin.

Dom (24m 44s):

We did see a trend for increased p yy. So, and that was, you know, may factor in with the appetite suppression. But I would disagree that, and my glucagon is normal, you know, my insulin is normal, everything's normal. I measure my CATA and things like that, everything's normal and you know, if something was gonna be outta normal, I've been on the diet for a long time, we do not see a decrease in glucagon. I I think it's important to note that in diabetics, so diabetics have elevated glucose because the amylin is not there and, and you have accelerated glycolysis and glucogenesis driven by, by glucagon in that context.

Dom (25m 29s):

But if you take non-diabetic people who just have a little bit of weight to lose, like their insulin drops a little bit, not statistically significant in our cohort of 35 patients, but I think if we had a hundred patients, we'd see that significant and the glucagon was pretty much normal. What I think happens though, the first couple weeks, so we just, we have a time, we have it at time zero six weeks and 12 weeks. And I do believe in that first two to three weeks you're probably gonna see an elevation of of cata coalmines and cortisol and glucagon. But we're not, we're not capturing that. And then so that, that basically leads into this idea that the body adjusts over time and if it was a chronic stress, it would show up in all these hormones and we're not seeing it.

Dom (26m 19s):

I do, I mean I met with someone this morning that it's amen Aric because of the ketogenic diet and their weight has been stable. So, and in females that follow the ketogenic diet for management of epilepsy, they're five times more likely to be a manure when they get to, when they get to like adolescent age and pass adolescent. So there's something going on there that we don't understand. And my, when I, when I got asked this question in the past, I would say, well yeah, well the, the athletes that are doing it are these cross CrossFit females that are, they're, they jump on a ketogenic diet, they are calorie restricting and they're over exercising.

Dom (27m 4s):

And that's leading to this triad of effects that are inducing that. But I've come to believe now that that female hormones are, can be significantly impacted just from the, from the actual, you know, clinical trial data from in, in the world of epilepsy. The only studies where we actually have very good data for the ketogenic diet is these controlled clinical trials for epilepsy. And that would show an increase in kidney stones and increase in triglycerides and some people ldl, we can talk about that a little bit and, and the aim in it's, it's a very real phenomenon.

Brian (27m 50s):

Jan, any thoughts regarding that?

Jay (27m 52s):

Yeah, it's, it's interesting to, to hear the, the data, right and to see potentially not an increase in glucagon. That certainly isn't what I've seen from the vast majority of data regarding and some of it likely on animal models looking at, you know, lowcard diets, which again, lots of potential issues within the, the diets and methods that are used. Maybe it wasn't fully ketogenic and whatnot, but largely I have seen generally we see, I've seen it an increase in glucagon tend to see an increase in reverse T3 again as a result of that, both, you know, and on I wanna say as well on ketogenic diets, I would have to, you know, go back through it. But the, so, so, and I think it's interesting as well that we do see at least an impact on female hormones, which I think the assumption would be we would see the same thing in males and that would have to be mediated somehow.

Jay (28m 44s):

Of course there could be, it could be all like maybe there's no hormonal regulation and it's just due specifically to, you know, fat oxidation leading to lack of ATP and, and that impairing testosterone production sort of thing. But I, or, or again, decreasing thyroid activity, reducing star activities or reducing the cholesterol uptake to convert to steroids. But I would, as you know, I've, I don't know what the, what other hormonal connection there might be or what other hormonal intermediate there might be other than glucagon to kind of mediate that process. But yeah, I don't know if you have any ideas there, but either way I, yeah, that that's, it's interesting to, to hear that data that you've, that you're collecting now.

Jay (29m 24s):


Dom (29m 25s):

Well that's why we measured amylin and I thought cuz amylin controls glucagon and, but we've directly measured glucagon and insulin and g i p one and, and grin and all the different hormones. So I expected actually to see an increase in glucagon. There is data in humans to show that athletes, that elite level athletes, this could have been, I forget who is the author of it, I have it, we're gonna reference it in the paper, but, but there's at least one study showing that athletes that have a high level of output in that exercise, like four to six hours a day or whatever have like almost doubled the amount of, of glucagon.

Dom (30m 9s):

And of course that makes sense. So we are proposing that this was one of the things that would show up in our, in our study, but, and normal people who are sedentary who just wanna, you know, use the diet to drop their body weight. We did not have a u caloric diet because we were looking to optimize metabolic biomarkers and we're analyzing the CGM data now. So we're looking at all that data now. But yeah, the glucagon just doesn't really, it's kind of uninteresting and I was really a little bit almost questioning the insulin and we, we use two different labs to measure insulin, so we're gonna compare, we used the blood spot card by ZT Labs, but it, I think we have, you know, blood work too through Quest to look at the insulin and compare that to make sure, you know, there's, you know, both labs were, were correct, but, but I really ju do think, like with the diet when it comes to diet, you know, the big thing people are trying to lose weight and, and I am a believer of the calories and calories out.

Dom (31m 13s):

So I, in that way I, I'm a little bit in the middle, you know, in from, from the perspective of a high carb approach or low carb approach. But I also believe that what we eat determines profoundly how much we eat. Right. And, and I've also observed, and I just gave a talk to the med students about this and just showed diabetes management with the CGM u caloric before and after from a high carb to low carb. And the CGM data looks like two different things. I mean, you'd see while the postprandial excursions and then, you know, trying to chase it with insulin and then dropping.

Dom (31m 56s):

I think what's most important is that someone who has type two diabetes and dare I go out on the, on the platform to talk about type one diabetes. You could go, if you google Andrew Konik TEDx talk, he was my former PhD student, he studied cancer Kecia for his PhD, but he is a type one diabetic and when he joined the lab, he was just transitioning to a low carb ketogenic approach for type one diabetes and, and it had a remarkable effect, you know, on his brain, on his productivity and everything. So he uses that approach and he, he works very closely with the American Diabetes Association and all the major players and diabetes and gave a TEDx talk on it talking about, I guess what would be called the Bernstein approach, which is basically carbohydrate restriction and carbohydrate management for type one diabetes.

Dom (32m 51s):

So I'll defer to, to his website and TEDx talk on that. He's really on top of that topic. But, but I, I was asked at the American Diabetes Association to give a talk on a high carb diet versus a low carb diet in, in type one diabetes or diabetic patients that were, that were athletes. And, and my kind of pitch was that any diet that could optimize your glycemic management was going to be optimal for exercise performance. Granted, that's in the context of, of diabetes, right?

Dom (33m 33s):

So, and also we know with type two diabetes that postprandial excursions and wild fluctuations in glucose are associated with a whole host of comorbidities. So the question that we're actually working on with my medical students, we're working on a sculpting review because this topic is such a nascent area of research. Does wearing a continuous glucose monitor and actually decreasing your glycemic variability, does that have any beneficial effect on, on various outcomes? And we're, you know, analyzing the data to figure out, to look at all the different outcomes.

Dom (34m 15s):

And what's striking is that there's not really good data on non-diabetics with CGMs, but we are under the impression that there's probably gonna be a signal there, but you, we might need about five more years of data in non-diabetics to show that that, you know, preventing wild fluctuations in your glucose would lead to better performance metrics and you know, maybe a shift in in in biomarkers too, but the data's not there yet, so I can't can't really say that.

Jay (34m 51s):

Yeah, so, so to kind of go back through a little bit with the glucagon piece, again, knowing that there is glucogenesis and ketogenesis going on in, in, you know, a state where someone's on a ketogenic diet, glucagon normally is the driver for those. So yeah, I wonder what is driving those, Obviously low insulin and, and elevated glucagon tend to be the driver. So I'd be curious to, to know that. The other thing I would point out, so you mentioned this, that in athletes you especially see the elevated levels of, of these stress hormones. And I've certainly seen research suggesting that there's increased sympathetic activity without carbohydrates available. You know, if someone's on a high fat, low carb diet versus if there are carbohydrates available, which I think is potentially something that point to as well.

Jay (35m 39s):

But I think the piece that we, to kind of circle back toward what you were saying at the end in regard to diabetes, we certainly agree that, or at least it sounds like we agree that if somebody is, doesn't have good insulin sensitivity and is not managing glucose well or managing their blood glucose well, they're normally better off on a ketogenic diet than continuing to have that poorly managed blood glucose and, and insulin resistance. And so I do think that that's an area where low carb diet helps a lot. I, I don't necessarily agree that it's the best way, but I think that it's a, it is effective in a state where somebody's insulin resistant and essentially not metabolizing glucose Well, and I think that is something that you mentioned in terms of epilepsy as well, right?

Jay (36m 21s):

There's elevated lactate production issues along the electron transport chain, excess oxidative stress with the glucose oxidation as it is. And so supplying keytones in place of that tends to lead to resolution of that issue. And so I think there are a couple areas where low carb diet shows benefits. One, one being that it brings relief from inefficient glucose oxidation, somebody is insulin resistant if they're not oxidizing glucose, well if they're in a, you know, type two diabetic state and having ketones on fat is going to be better off. But my approach would be rather to improved to the extent that can be, and maybe in certain cases it can't be, but I think the vast majority of of cases that are lifestyle induced, that inefficient glucose oxidation can be improved upon and can, and proper glucose oxidation can be restored to allow for proper insulin sensitivity.

Jay (37m 12s):

And so that would be where my focus would be. And I think there's, beyond just the key tones displacing glucose potentially, or the fat displacing glucose, I think there are some other mediating factors as well where a low carbo KIDOgenic diet can really help to improve glucose oxidation, especially in terms of the gut effects. So reducing endotoxin production and exposure or lip polysaccharide and that being something that is a major driver of insulin resistance and poor glucose oxidation. And I think a low carb diet is really great at relieving that. Again, I think there are multiple ways that we can do that and I'd prefer personally not to go that low carb ketogenic route because of the potential stress effects. But that's, I don't know if that helps maybe kind of encapsulate more of the, the direction that I'm coming from here.

Dom (37m 57s):

I'm, I'm not aware, I mean just there's one paper in athletes, but I don't, you know, I would put, I would not put me in that category or the majority of people, I'm not aware of human data, like randomized controlled trial data really to show that there's a stress response. And our data certainly does not show that we do have a day, we do have data, fresh data that we're preparing for a publication on low carb, high fat versus high carb, low fat. It's a crossover design. So these are fairly elite level athletes. There is 10 of them. And I'm looking at the data now, the most striking thing that comes out about this data is that 30% of the high carb low fat athletes, 30% of them had a baseline blood glucose over 100 milligrams per deciliter.

Dom (38m 57s):

So it was u caloric. So we tightly controlled for the calories, same amount of calories and low carb, high fat versus high carb, low fat. And the, what was interesting is that the greatest glycemic change and peak fat, fat oxidation state was actually in people who were high carb, low fat that switched over to low carb high fat. And then their peak fat oxidation state was determined by the delta change in the glucose, meaning that they started at a high glucose and from high carb low fat and they switched to low carb high fat and their, their glucose went, they were athletes metabolically fit obviously, and they were prediabetic because they were following a, a high carb approach and they were not gaining weight or decreasing weight, but they had significant decrease and glucose and, and they, they actually ended up being the highest rates of fat oxidation.

Dom (39m 58s):

And then we have all the, the data and we have a massive amount of data for this and hopefully it'll be published within a month or two. But what was very interesting from just a baseline perspective is that the low carb, high fat group in the, this is 31 day study, none of them all I would, I'll restate all of them, had a baseline glucose that was under 100 milligrams per deciliter, whereas 30% or more of the 30% of the high carb group, they were elite level athletes. Their, their glucose, the, there were two distinct lines on their cgm.

Dom (40m 38s):

Now whether that's important or not, you know, so I think there's been a lot of chatter online about, you know, if you eat rice and your glucose goes up and you have these spikes, is that a bad thing in a, in a healthy person? I don't think it is. But what happens with me and what happens with other people too is that in about two hours you get the postprandial dip and you get a mild signs of, of a little bit of hypoglycemia and then you kind of get hungry again. So what I've experienced, and it doesn't have to be a ketogenic diet at all, it's just switching from maybe 60, 70% carbs to 30% carbs, which is, which is like moderate carb and high fiber and that that can pretty much abolish or attenuate significantly those spikes.

Dom (41m 30s):

And then you have very good carbohydrate management. So, so I think that's prob my, my opinion is that for the majority of athletes that that the low carb, a very low carb approach probably is not optimal, but just carbohydrate management and being metabolically aware of your glucose and because if you're, if you're basically just fueling your body from a high carb approach, you become metabolically inflexible. So the idea then is to, if you're an athlete is to periodically go low carb, maybe do some intermittent fasting here and there, but I think from a, from someone to who's metabolically healthy, my approach would be to basically try to promote metabolic optimization by enhance metabolic flexibility and being able to use fats and carbs.

Dom (42m 20s):

And I think the true test for metabolic flexibility is just not eating for 24 to 72 hours. And if you completely crash and have a hard time with that, you're probably not very metabolically flexible. Whereas if, if you seamlessly transition from burning glucose and carbs to burning fat and keytones, then that's probably a pretty good sign that you have good metabolic flexibility.

Jay (42m 48s):

Yeah, so, so there's a handful of different points there In terms of the, so I agree, I agree that we would want to titrate carbohydrate intake to tolerance. I also think that we would want to adjust the factors that would allow for quote tolerance or I would just say efficient utilization. And I think there's a handful of factors to consider. So one of course we don't wanna see extreme spikes in blood glucose that would either be due to a very, very unbalanced meal in somebody who's not very insulin sensitive or just a lack of insulin sensitivity to begin with.

Jay (43m 28s):

And then seeing, seeing that dip in crash following. So for, you know, for maybe an average person, I think having a relatively balanced meal that includes carbohydrates, fats, and and protein, which tends to slow digestion as you mentioned, also typically including fiber will tend to mitigate that sort of response. And I think it's somebody who has very efficient glucose oxidation and good insulin sensitivity. Having something that's more car-based without as much fat and and protein should be less of an issue and shouldn't cause as much of a spike. And if it did cause a spike, it would be coming down back toward baseline quickly because that glucose would be utilized effectively in terms of metabolic flexibility or inflexibility.

Jay (44m 8s):

Part of my objection there for one is that I think it's the oxidation of glucose that tends to be far more sensitive to environmental issues stimuli, various toxin exposure, whether it's the polysaccharide or mercury or cadmium, whatever, whatever it is that when we're exposed to those states or if we look at any state that is characterized by a more extreme exposure there, whether it's fatty liver disease or type two diabetes, we tend to see the fatty acid oxidation, the lipid oxidation being highly upregulated and that being induced by stress hormones. You mentioned elevated gluconeogenesis of course is elevated lip lysis as well and those tending to drive a state of both increased lipid oxidation but also lipid storage.

Jay (44m 54s):

And that's part of my, I guess again, the issue that I take with the idea of metabolic flexibility, which I don't know how much this pertains exactly to fat loss and whatnot, but I would basically regard fat oxidation as the default state that we resort back to when we're under stress or when we can't oxidize glucose. And I think for the vast majority of people, the ability, the capacity to actually oxidize glucose efficiently is where the, the issue tends to be. And so when we, we should see, when we shift from a moderate or high carbohydrate diet to a zero carb diet, we should see increases in glucagon adrenaline, cortisol, we should, I would say feel a stress effect from that.

Jay (45m 36s):

I think that that's the normal shift from glucose to fat oxidation and then gluconeogenesis and ketogenesis, those are the normal hormonal regulators of that state. And so I think we should feel that difference. I don't know if it should necessarily feel good or if we, if it would be a good idea to not have any effect there. And I think this is why a lot of people might want to use exogenous keytones to help shift that faster. So that,

Dom (45m 57s):

So I'm gonna interject there. So, so the stress response I actually agree with like when you go on a ketogenic diet, there's an elevation of cortisol calomine and glucagon. But I believe my, my view is that that's a beneficial thing that helps facilitate greater fat adaptation. And then those things, I mean according to our data and most published data is that these things just come back with a u caloric diet will just come back, back to normal. It's much like, you know, if I get under the bar and squat 500 or whatever, that's a stress and it releases all sorts of crazy things, right?

Dom (46m 38s):

But from my contacts, it's from my contact, it's the adaptation to that stress that is most important. And I think some people definitely communicating with them, they absolutely fail to adapt to a ketogenic diet and they do it and they're actually losing weight, but their triglycerides go up and, and their, you know, LDL goes up and their blood glucose does not go down. And for reasons I don't really know, maybe they have some snips, they're just, they're just not good fat oxidizers and most importantly they don't, they don't feel good. They have a lack of energy. But if you go on a ketogenic diet and you sustain it, the benchmark is if you have lots of energy, if you're on a ketogenic diet and you're burning fat and ketones instead of glucose primarily and you feel great and all your metabolic markers are great, then it would be hard to argue that that's bio energetically unfavorable if you have energy.

Dom (47m 34s):

So how could it be bio energetically unfavorable if the person has tons of energy and all the biomarkers are good.

Jay (47m 41s):

So, So to bring it back, cuz I, you brought up a lot of points I do want to come back to, but in terms of just the metabolic flexibility and using a shift into ketosis as a test for that, that was kind of my resistance was we should, as you said, the, the increase in stress hormones is a normal part of that. You know, people might talk about keto flu or whatever is involved in feeling negatively during the shift in, and I would say if you feel negatively there, that's not a sign of metabolic inflexibility. That's what I was getting at. Now if you're already, if you're already on the ketogenic diet for let's say multiple weeks and you're having trouble adapting, then yes, maybe there are some potentially genetically induced issues with fat oxidation or something along those lines. But in terms of just coming back to the metabolic flexibility component, I was just taking a bit of an issue with that as being a good test.

Jay (48m 27s):

And rather I would say how well does someone do to a glucose challenge, especially, you know, if someone's on the low carb diet, of course we know that that's not going to go too well. But I would say in general, insulin sensitivity or glucose ox oxidative capacity is normally more limiting. And so when it comes to metabolic flexibility, that's, that's the issue I have is I think people tend to focus on can you oxidize fat? Well I think the number of people who can't oxidize fat well is very, very small and may, I don't know what sort of mechanistic things might be going on there as you know, I know you said you don't either except for maybe some snips, but I think there are a ton of things that will inhibit efficient glucose oxidation and we see that with the tons of people with insulin resistance. And so when it comes to metabolic flexibility, that would be more of where I guess my test would be is how well are you exercising glucose?

Jay (49m 10s):

Cuz I think that's more of the, the kind of challenge for the average person.

Dom (49m 15s):

Yeah, and I think for athletes, if we're not talking about someone with a deficit with athletes, so as I mentioned, so my approach if you're metabolically healthy is to optimize metabolic flexibility. And my definition of metabolic flexibility is to formulate your diet in a way that optimizes carbohydrate tolerance and that optimizes fat tolerance and, and keto production. So that could be, I think my opinion is that would be a mixed diet that's a little bit lower in carbs and keeps your body kind of hungry for carbs. And that can actually upregulate the, the glu four transporter, keeping your body a little bit hungry for carbs will enhance insulin sensitivity and actually facilitate glucose disposal in the context of a glucose bolus in the context of a ketogenic diet that's sustained or a very low carbohydrate diet that's sustained.

Dom (50m 11s):

There's no doubt in my mind that Piru Bay Dehydrogenases complex becomes not only, and I've seen data on this, that the actual protein levels when you do PCR get is lower and the catalytic activity of that is also decreased over time. So, but, but it, but it takes a relatively small amount of carbohydrates to get that enzyme back up to normal. But for like a large male that could be 200 grams of carbs a day, you know, and for a sedentary person it could be 50 to 75. So, so you know, eating 4, 5, 600 grams of carbs a day seems unnecessary.

Dom (50m 52s):

And I, from the data that I see, you see some pretty big fluctuations. So my my opinion is to probably like my opinion for the optimal diet would be to cut carbs way down and, and then titrate it to where you're optimizing carbohydrate tolerance. And, but yeah, there there's no doubt that, that when you restrict carbohydrates and you maintain that you become carbohydrate intolerant. And if you do a a glucose challenge, you're gonna see that. But, but that adaptation comes back pretty quick. So when you reintroduce carbs, probably it takes about two weeks. You could actually convert someone who's completely carbohydrate intolerant to carb tolerant, like that metabolic machinery seems to upregulate pretty fast.

Jay (51m 39s):

Yeah, and I don't think that's pathological, right? I don't think No, no,

Dom (51m 42s):


Jay (51m 42s):

Yeah, to be in that low

Dom (51m 44s):

May be beneficial. It may actually be beneficial. I actually, and I've talked about this, although I don't, I think the data's, I don't like to speak outside of the actual data, but, and I, I think this conversation maybe came out of just talking with Lane Norton and as he, as he coached like the first time he coaches people for, for like a body building show to get them in shape, it's, it's so difficult but one, you do it over and over again like each year contest or whatever is that it's almost like their body knows what to do. And when you activate all those different pathways for fat oxidation, and he does it in the context of a high carb diet, so he's actually bringing patients down or patients athletes down to extremely low levels of body fat and keeping their carbohydrates as high as possible.

Dom (52m 33s):

And this is completely achievable if you kind of, you know, just balance your, just through energy balance, right? And just decrease the total caloric, my opinion is that that would be a little more painful then restricting the carbs to the point where you're elevating keytones and then the keytones kind of keep brain, brain energy metabolism kind of in check because if, you know, most people are trying to lose weight and if you do it on a carbohydrate based diet, you're gonna have fluctuations in glucose and you're definitely gonna get lows in your glucose. I remember experiencing this eating like just rice, like fish and rice and like two hours later I would, and that was essentially abolished when I switched out the rice right.

Dom (53m 17s):

And added some vegetables and added like, you know, extra virgin olive oil and my blood glucose was much more stable and with the same amount of calories. So, so I I I think, I think it's important to just carve moderation is important and maintaining that flexibility, but I do from your perspective, I, I think that there could be a danger in restricting carbohydrates for too long and essentially making your, making you carbohydrate intolerant to a glucose challenge that that's very obvious. I've seen that quite often.

Jay (53m 54s):

Yeah. And I, I don't see any issue with being in a state where someone's relying on, on fat oxidation and then is not going to be glucose tolerant. I don't see the lack of glucose tolerance in that state as the problem. I, I think it's just a, a normal adaptive feature of relying on fat oxidation and, and as you said, for example, downregulation of ate dehydrogenase, which of course insulin is, is going to majorly stimulate as soon as someone gets carbs in, you know, consistently and and whatnot. So yeah, I don't, I don't see an issue with, with that per se, but I think it's somebody who is not physiological insulin resistant and someone who is what we, what's called pathological insulin resistance, but you know, largely the same or very similar mechanisms where they're able to only consume, let's say a hundred grams of carbs without seeing those major fluctuations or without seeing, you know, without saying some sort of negative effect.

Jay (54m 47s):

I think that that is an issue that would, instead of just reducing carbohydrate to tolerance, I would want to actually sort out what is the driver of that lack of tolerance or that lack of oxidation and work on sorting that out. And again, I'm not saying here to then go on a super low fat high carb diet, I tend to prefer let's say 40 to 55% carbs and maybe 30 to 40% fat, 25 to 40% fat. For myself, it's, it tends to be higher. I, I think based on activity and, and muscle mass, I can, I have a better fat sink, but the, yeah, I'm not talking, you know, super low fat here, but I think that I, I think that we are addressing a symptom, we're responding to a symptom as opposed to actually addressing the root cause, right?

Jay (55m 34s):

And so if we take the extreme example of type two diabetes, yes, low carb is going to result in much more stable blood sugar and great improvements in how they're feeling and probably weight loss and and whatnot through a handful of mechanisms. But I would say yes, do that, you know, reduce carbs to tolerance to whatever extent needs to happen. But let's actually fix the, the impaired glucose oxidation that has come about over years and years of degenerative processes and as you said, aging, which I think is not just a byproduct of aging, but rather is the aging itself is literally impairments in the process of mitochondrial respiration.

Dom (56m 8s):

I I think we're totally like on the same page and I, and actually I can appreciate, understand, and actually agree with the perspective that if you are an athlete, and it maybe most people listen to this are an athlete, but most of people I work with or in our studies for clinical trial or not, and most people are just generally are not athletes, but if we're dealing with an athletic population, I think it's best to almost coach them and train their metabolisms to be maximal glucose oxidizers. So to actually titrate the carbohydrates in might be best to use that with a CGM and gradually adjust and gradually increase the carbohydrates over time to basically assess their maximum carbohydrate tolerance and just, and, and then that could be introduced during the actual event.

Dom (56m 58s):

Right? But I, but I do think that having periods where you are decreasing carbs and keeping it kind of low can kinda reset insulin sensitivity after a period of carbohydrate surplus over time. I think the issue comes in is that the majority of people to get benefits, body composition, alterations and favorable changes in biomarkers that are most important, insulin hs c r p triglycerides, especially triglycerides hemoglobin a1c and glycemic variability as measured through cgm, that some degree of carbohydrate restriction independent of calories on a e caloric diet will lead to favorable, slightly favorable changes in, in those things in body composition.

Dom (57m 49s):

And, and I think, but I think it's kind of small and I think the, the main driver for changes in favorable changes in body composition alterations and metabolic biomarkers, cardiometabolic biomarkers is undoubtedly at caloric deficit, right? If you're taking subjects that are, is undoubtedly a chloric deficit and my opinion based on just doing clinical trials and actually doing mouth trials too, so a ketogenic diet is hypo palatable and fairly hyper satiating. So it, it becomes like kind of an easy way to produce a calorie deficit. And then you see all these benefits and there's quite a lot of studies showing, hey, KIDOgenic diet lowers blood glucose, it lowers insulin, they decrease fat and it's, yeah, because you're just reducing calories, you're not eating as much because the food doesn't taste is good.

Dom (58m 40s):

So I, I think that the majority of benefits of the low carb diets and ketogenic diets are simply due to the ability of eating this, this macronutrient profile, the ability of this to produce in energy deficit through a mild state of color restriction. So we've seen this in mice, we've seen this in rats and the human data in many cases, that it's just humans are awful at recording the amount of calories that they eat. And some people say they could eat so much more calories on a ketogenic diet and still lose weight and have favorable changes in body composition.

Dom (59m 23s):

But I would argue against that, I would, I would say that the, the weight loss and, and fat loss and changes in important metabolic biomarkers like insulin and glucose are due 90% due to just creating a calorie deficit. But one thing that's not really debatable is that the glycemic variability will reduce significantly with a low carb diet and a ketogenic diet So the big question is, is that even important? So that's, that's something that we're researching now.

Brian (59m 57s):

And, and I'll just add one thing regarding that in the sense that, so I was, for my story, like I was low, I've been low carb for a while and you know, after just, I like to experiment, right? Like self experimentation and you talk about like certain genetic markers potentially having an impact. And I got a gene test and worked with someone and he analyzed the fact that I, I was like a slow metabolizer of saturated fat. And so we actually are looking to eat leaner meats and actually up the carbs. But I always like to teach the fact that it's good to track what you're doing for a few weeks to see like, where am I at? Because like for a while I'm eating two meals a day, pretty low carb and some, sometimes one meal a day.

Brian (1h 0m 43s):

And just noticing that yes, like you mentioned, you are full longer. Like I was not that hungry. I don't know if that's a good thing or a bad thing, but for some people it might help. But I think for a while there I was probably restricting calories too much and maybe causing impact on hormonal health. And I think this is, maybe Jay, to Jay's point a little bit, is that when people get into this mode for, for a while and they're restricting for so long and creating stress per se, that it might take a hit on hormonal health. And so I'm actually testing it the other way and seeing how I do on higher eating more carbs.

Brian (1h 1m 23s):

It's, I will say if you go low carb for a while, it's tough to bring in those carbs. It's like, you know, I, what, what I will say is if you're gonna add starches, at least for my personal view, add 'em in at the end of the day. Don't, don't add don't have a baked potato in the middle of the day or rice because you'll probably be knocked out and feel, feel it. So I've been adding in more like fruits and things like that in, in the beginning of the day and for my first meal. And those I find, and I wear a cgm I don't have one on right now. Those, the glycemic variability on those is, is minimal compared to, I remember I, one time I, I made a sweet potato, had it in the middle of the day and I was like falling asleep, fall asleep.

Brian (1h 2m 5s):

Yeah. And, and the CGM read read, I looked and I was like, whoa. It went to like, I don't know, one 50 and, and, and obviously eventually came back down. So

Dom (1h 2m 14s):

Oatmeal too will do that. Yeah. So, and it's

Brian (1h 2m 18s):

Interesting cause a lot of, a lot of of bodybuilders will start the day with oatmeal, which I don't really get

Dom (1h 2m 22s):

That. Oh, I did for, for many years. Yeah. But, but lentils, something like lentils actually has a significant amount of carbohydrates and I have like almost a flat line on lentils. You know, it's, it's very mild if you are reintroducing carbs back in, I would actually take alpha lipic acid, alpha lippo lapic acid is part of the piru dease complex and alpha lipoic acid comes as a smic mixture of r and s. And I would recommend using the r and antier of, of alpha poetic acid at about 400 milligrams with carbohydrate.

Dom (1h 3m 3s):

And you'll probably see that significantly lower. Maybe burberine something too, but alpha lipic acid is a good way to fire up and get the p functioning again. It's part of the P complex actually. So that would be, and then choosing something like maybe just getting, just eating more veggies, but lentils are, for me at least, is a good way to introduce carbohydrates back in

Brian (1h 3m 28s):

Jay. Any thought, any thoughts on that? Well,

Jay (1h 3m 31s):

So I just missed that. I don't know if you saw my, my camera shaking. We just had a small earthquake, so I don't know if it's totally done yet. So

Brian (1h 3m 39s):

I was wondering, sorry I

Jay (1h 3m 40s):

Missed most of that.

Brian (1h 3m 41s):

That's my first interview with an earthquake. It it

Jay (1h 3m 44s):

Same, but I think, I think it's,

Dom (1h 3m 48s):

I think we're okay.

Jay (1h 3m 49s):

Yeah, sorry, sorry about that. So no problem. Talking about different carb sources, right? On blood glucose.

Brian (1h 3m 55s):


Dom (1h 3m 56s):


Brian (1h 3m 57s):

And also, and Jay, I'm curious, know your thoughts. I know, do you bring up calories and calories out? And Jay, I know you've had some podcasts on that and I'm, I'm mixed on that. I think it, it, it's, isn't it almost, it's very difficult to tell like what is your calorie output per se, and how can you even know? I, I feel like there is a bit of a guessing game. So anyways, I'm Jay I'm curious your thoughts on that as well.

Jay (1h 4m 22s):

Yeah, yeah. So from carp, the carb source side, I would agree that, you know, fruits especially between the balance of glucose and fructose and also the, the fiber that tends to lead to a smaller glycemic response with the fructose having a suppressive effect there, having a mixed meal tending to be beneficial, you know, ideally I think we would wanna be in a state where having some potatoes or sweet potatoes doesn't completely zonk us out, but when you're transitioning from lower carb, it might take a while until someone's at that state and you know, have more glucose capa storage for glycogen capacity, things like that. But As far as calories and calories out goes or, or just the idea that low carbo KIDOgenic diet is beneficial because of, of reducing calorie intake.

Jay (1h 5m 10s):

So I do think it is good for that. Right. I know normally we would see those effects on, on grin and interestingly in in the data you were talking about Dom, you weren't actually seeing that at least in again, what what you had there. But normally in, you know, normally it's, that's looked at as, as part of the reason for reduced appetite. But I would actually say that I think there are other reasons why a low carver ketogenic diet is, is beneficial. That would not be just because of, of reducing calories or would be entirely independent of that. And I think that would come down more to effects on the gut and the gut bacteria as well as, as I was saying before, relief from inefficient glucose oxidation, if there's any sort version of insulin resistance going on.

Jay (1h 5m 54s):

And I think that those would actually be more powerful. And then the next point I would get to there is I think there are other ways that we can accomplish those things that don't require the same, the same removal of carbohydrates. And so maybe that's something we could talk about. But Brian, to your point, as far as calories and calories out being extremely difficult to measure, I would certainly agree with that. It gets, I mean, it's nearly impossible to accurately measure either. And I think what a lot of people default to is, well, if you're gaining weight, you must have been in, in a surplus. If you're losing weight, you must have been in a deficit and you have to reverse engineer it like that, which is a problem from a definitional standpoint. But you could say that it, that it works as far as regulating food intake.

Jay (1h 6m 34s):

But it certainly is very difficult in practice because every food that we eat, the timing of the foods, what we're doing throughout the day, sunlight, exposure, sleep, whatever else is all going to affect that calories outside. And on the calories inside we have estimates of, of how many calories are in any particular food. But there's some interesting research showing that sometimes those estimates are off by as much as 25% and there's one on almonds, those talking about that and also how much the processing of foods affects it, whether it's cooking or just like literally processing from whole food to, to processed version affecting the calories inside or actually how many calories get absorbed. And we have the digestive side too. How much is being absorbed versus how much is being excreted through those other means.

Jay (1h 7m 15s):

So I think it largely becomes so difficult or nearly impossible to actually measure accurately that you could use it as, you know, you could use the calorie intake as a, as a kind of general idea of how much food you're eating and then you can use your shifts in weight or body composition as reflection of whether you think you're eating too much or too little based on your current diet. But I think as far as just being, here's the exact number in an exact number out, I think that's, I would argue it's nearly impossible to measure accurately.

Dom (1h 7m 42s):

Yeah, you definitely need to collect poop. So we know this from doing mice and rat studies when you feed them ketogenic diet, it looks like they were actually eating like twice the amount of calories and we're like, wow, maybe the diet does, you know, is a metabolic enhancement, but the poop was like white. So our ketogenic diet is pretty high in, in MCTs and it's got, you know, a mix of different things, but it was very clear that they were pooping out a lot of fat and a lot of calories. So same goes, you know, Yeah. For, for human studies, well designed human studies, you have to look at this, for example, if you're eating like a bunch of raw ovens, you know, a lot of that, a lot of those calories are gonna go through you for sure.

Dom (1h 8m 25s):

I know for me at least, you know, eat a lot of nuts or, and then various fibers, you know, are converted to short chain fatty acids too. And I do think the gut microbiome is super important and relevant here, but there's just not enough randomized controlled trial data for me to talk about that. I, I think probably one of the most, the questions that I gotta ask most frequently is, you know, what's the KIDOgenic diet doing to the microbiome? Do low carb diets have a favorable effect on the microbiome? All I can say is that I get, I get quite a lot of emails every day about a hundred from different people and I scan them just to kind of extract information and there's, there's, and I get back to as many people as I can, but people who have ulcerative colitis, people who have a Crohn's disease or IBS or any form, they seem to have a favorable response to a carbohydrate restricted diet, interestingly to carnivore diet, which I'm not, you know, super fan of.

Dom (1h 9m 30s):

But, but nonetheless, I can't argue with the data anecdotal that it is that they're getting a favorable response from eating zero carbohydrates and zero fiber. Although I do not think it's a, a longevity. I don't know of any centenarians that are carnivore. I don't know if you, but I was, I was watching something last night on Netflix about I think at the Japanese and there is basically all they, this one population is all, they basically a rice based diet, so it's just basically super high carb diet and they were talking to this one lady, she was 120 years old, at least 120 years old, but there was no birth certificate when she was born in the 18 hundreds.

Dom (1h 10m 11s):

And all she's eaten all her life was rice. And a lot of this entire population of people, they're all over a hundred and they're basically eating. And it made me think, man, there's, I don't think there's any like carnivore centenarians out there. Maybe there is, I don't think it's, it's probably not the optimal longevity diet.

Brian (1h 10m 32s):

And it, Jay, I've heard you talk about this. I'm curious, I wanted to ask you regarding ancestral eating and you talk about like the bonobos and the amount of fruit that they would eat, like 60% of their diet maybe you mentioned, and I'm just curious your thoughts around that.

Jay (1h 10m 50s):

Yeah, well so as, as Dom was pointing to, there are quite a few cultures that we know of currently that are very high, you know, eating very high carbohydrates, especially in those blue zones. And I don't think it's just coming down only to carbon intake versus fat intake or anything like that. But I think we can at least safely say that high carb diets do not mean shortened longevity based on those things. And you know, we have the CATA Tobins, there's the OK and balances, there's, there's a couple of others and you know, and they also have really, really amazing glucose tolerance or, or you know, performance on glucose tolerance tests. And so I think that's noteworthy that oftentimes the more that we're izing carbohydrates, the more favorable our body shift toward being able to oxidize them.

Jay (1h 11m 36s):

And similarly with fats, right, we were talking about that too. If you're on a no carb or low carb diet, you'll be oxidizing far more fat as as a fuel.

Dom (1h 11m 44s):

Yeah. And, and I think that there's a a y one mutation that is quite high for amylase, you know, and it doesn't make sense that if we have very robust high copy number of amylase, so the za the Japanese, you know, kind of have very high copy number of this amylase that it makes sense that we were sort of genetically designed. But some people I think lack that, you know, or don't have as as high copy number. So I, I think this is a fruitful area of research and I was in, I don't study that but I was, you know, sat in on a couple talks about this and that the, you know, this am you know, amla's mutation is being looked at to assess carp tolerance.

Dom (1h 12m 33s):

So maybe it comes up as part of your 23 and me when you put it into different platforms, your prescription, you know,

Brian (1h 12m 40s):

I put my 20, I put my 23 and me in Rhonda Patrick's, she has like a free, you know, sort of, I don't know, free thing on her website where you can sort of get an analysis. And so it's interesting what you can learn nowadays through the, through the gene steps. Yeah, go ahead Jay, are you gonna say something?

Jay (1h 12m 58s):

Yeah, well and amylase of course is most relevant when it comes to starch intake and I think sugar intake through the form of fruits and, and honey is, can also be a considerable carb source and depending on the population is, and so you mentioned the bonobos who throughout the year getting between 60 and a hundred percent of their diet from fruit, there is a lot of fiber in that fruit as well. So they are also getting a lot of sort chain fatty acid production as a result of that fruit consumption, but still ends up being a very high carbohydrate diet and high sugar diet. And yeah, and this is a little bit of a tangent from I guess or conver conversation, but when you look in, in throughout apes, the increased, the ones that rely more on fruit intake over leaves and, and more foliage and more fermentation, there tends to be an increase in intelligence.

Jay (1h 13m 46s):

And, and I think that that's, there's a handful of mediating factors there, but I think there's a suggestion that we don't wanna be relying on fermentation and, you know, as a major source of our, of our calories or of our substrate and instead would want to be relying on easily digested food sources like fruits and also meat and, and fats that are digested pretty easily.

Brian (1h 14m 10s):

Yeah. What what about, you know, we talk about like optimal health, you know, I think everyone has like a different term for what that is and I think one of those is, is like thyroid health. I'm just curious cuz I know just researching over the last few weeks, I mean you've talked to different people but you've seen some stuff that could keto or low carb causes hypothyroid, thyroidism. And I'm just curious to know your thoughts and, and Dom if you've seen this in any of your work regarding long term, you know, low carb, if, if that could cause a adverse effect on thyroid.

Dom (1h 14m 48s):

I've not seen it in myself. My T3 trends to be in the upper high range and my t fours normal and my T ths has been normal. So, you know, if I would've seen, I would've seen something happen by now. But with, with females doing keto and with people using a ketogenic approach in the context of high level of exercise or in the context of a calorie deficit, yeah, I've, I've seen low T3 and a decreased conversion t t T4 to T3 or so that, that seems to be quite common, but it tends to be sensitive to insulin cuz insulin I think does activate the conversion that the iOS enzyme, the T4 to t3.

Dom (1h 15m 37s):

So I, I think there's something there, but it may be very individual and may maybe very context dependent.

Brian (1h 15m 44s):

Yeah. Jay, thoughts on that?

Jay (1h 15m 46s):

Yeah, I would, I would largely agree that if someone's in a context of elevated stress, there's certainly going to be more likely to see that impaired conversion if you know, along with the low carb or even without right elevated stress regardless of whether of carbon take. But then especially I would say in a, in a low carb state, you will see the, the reduction in d and d and ACE enzyme activity, the reduced conversions from T4 to t3, the elevated reverse t3 I've certainly seen, you know, had people come to me with, with those issues. And it tends also to correlate with a trending up cortisol as far as fasting cortisol trending up, fasting glucose, which of course is not only not always the case, but certainly something I've I've seen commonly and I think happens quicker or to a greater extent when somebody's low carb but not ketogenic if they're, for example on a carnivore diet and relying heavily on glucogenesis without the keto gen, without the ketogenesis and still relying to a much larger extent on carbo station, but getting a lot of that from the protein that they're taking in as opposed to shifting into actually fully ketotic state.

Brian (1h 16m 51s):

And, and Jay you talk about like empiric glucose metabolism. How can someone improve that? Like what, what steps, I know you talked about gut health is that, and, and we haven't even touched on like the rise of vegetable oils and I'm sure Jay you have some words on that, but what, what are your, you know, what, what would you say to someone looking to improve glucose metabolism?

Jay (1h 17m 13s):

Yeah, so that's where I tend, you know, I tend to focus the conversation is right is on these things that can impair proper metabolic, you know, mitochondrial respiration, proper glucose oxidation. And when that's not happening tends to shift us toward toward fat oxidation. And there are a lot of things that will cause that. So you know, as far as looking at indigenous lead produce things, we have the generic stress hormones that we talked about already, how those cause that shift. But there are a lot of external factors that can create that state. So you mentioned gut health and I would say that lip polysaccharide, which is also known as endotoxin, is really effective at doing that.

Jay (1h 17m 55s):

It inhibits the activity of complex four of the electron transport chain as well as complex one also tends to increase various inflammatory cytokines, nitric oxide, which then inhibits enzymes in, in the Creb cycle, particularly tase leading to a shift toward citrate buildup, which inhibits glucose oxidation and also leads more toward fat storage and fat oxidation. And so that would be a huge one. And this is, you know, lip ply saccharide is produced by gram negative bacteria in the, in the intestine, but there's a handful of other kind of toxic, toxic byproducts from different gut microbes that I think are majorly problematic. And we see, we see this in a lot of chronic health disease states. So you see low-grade metabolic endotoxemia in insulin resistance, diabetes, fatty liver disease, and and on end obesity.

Jay (1h 18m 42s):

And of course the severe version of endotoxemia is sepsis, which is a product of incredibly inhibited immune activity and and infection that tends to lead to death. And so I think that's a huge source of problems in terms of our ability to oxidize glucose and then also trend toward an inflammatory state and stress state that I don't think are conducive to health. And you mentioned poly saturated fats, I would say those are are another one. So you know, we can look at the omega sixes there and, and the omega3s as well. I think there's a couple of stepwise places that we would see those inhibiting efficient respiration. One of those just being the, well I would say one of the biggest ones is actually their incorporation in as fossil lipids in the inner mitochondrial membrane where they're actually have a porous activity that actually create permeability there that inhibits the, or actually allows for protons to move through the fossil lipid by layer as opposed to being properly kind of separated in order to allow for proper electron transport chain function.

Jay (1h 19m 46s):

And so through that mean that means alone they're going to reduce the efficiency of respiration. But then you also have the situation where when they are incorporated as membranes or when you just have 'em kind of floating around, they're very susceptible to peroxidation way more so than a monounsaturated or saturated fat. So as an example, if you look at dha, which is the product of omega, well it's an omega3 fatty acid, it's 320 times more susceptible to peroxidation than monounsaturated fat only eight. And you see radon acid is about half as susceptible, so about 160 times as susceptible to peroxidation. And so those peroxidation products will have similar effects as well where those are going to drive the state of uncoupling, the state of fat oxidation where we're not efficiently able to oxidize glucose where we're having trouble getting the ATP that we need without inducing kind of forced respiration through the cat coalmines or through glucagon, which will cause calcium influx and cause a dramatic increase in the rate of respiration to produce atp, but largely at a, at a cost.

Jay (1h 20m 47s):

And so those would yeah, be a couple of of things. I would say nutrient deficiencies would be another one as well. If we are low in thymine, we're not gonna be able to effectively oxidize glucose, you know, we're gonna have that inhibition of per a dehydrogenase and yeah, there's a handful of other nutrients of course that are involved too. So those, those would be just a few factors that would be looking to as far as why somebody might not be able to oxidize glucose efficiently.

Brian (1h 21m 12s):

Thanks for that. And Dom, anything else to share on that?

Dom (1h 21m 19s):

You know, I actually, it was kind of my wheelhouse studying pfas at the level of the membrane and memory lipid peroxidation. So I used to measure meeh and I actually developed the atomic force microscopy for biological applications to measure membrane lipid peroxidation as changes in membrane, membrane elasticity and membrane roughness. You can look at the BLE that happens to with oxidized POAs, but I'm actually on the fence when it comes to like the seed oils and pfas and the diet because the human randomized, you know, controlled trials and things like that do not really support that these things are dangerous or the data still not.

Dom (1h 22m 4s):

So as a scientist and you know, I I tend to just not so much common, I do believe undoubtedly that when you heat these things up, they create a whole chain of of oxidation lipid peroxide. So this is actually part of the redox biochemistry course that I teach, looking at all the different lipid peroxides and I've seen it, I've seen it in the lab, but when it comes to, you know, humans consuming off the shelf seed oils and things like that, I don't think the data's there to basically conclusively say, actually the data goes in kind of the opposite direction. It's like more phos is better than saturated fat, which is, you know, I don't believe that either, but I, but I don't think it's that much of a problem unless these things are heated up.

Dom (1h 22m 53s):

And I think that's why if you look at death rates and, and the health issues associated with fast food consumption where they're using these things and cooking in them and heating them up, then, then I think a lot of the health consequences associated with fast food consumption is linked to these seed oils and, but that's a bit of a stretch. So I'm a little bit reserved and hesitant to comment on. I've talked to Kate Shanahan and we've had a number, lots of long conversations about this and sharing publications back and forth. I do think she's onto something, but I just don't think the date is there yet.

Jay (1h 23m 34s):

And I would agree as far as randomized control trials, that it isn't there. I, one of my objections there, one of the reasons I think we could say that is because I, I found it to be very rare where there's actually a low enough p of intake to have a, an effect as far as depleting it, especially in the membrane. I know that it tends to be single digit percentages, I wanna say under 5% until you're really seeing a shift there. Yeah. And so I think that could be part of, part of the reason and, but I do think there's other relatively convincing evidence to suggest that they might be issues. And some of the great research that I would point to would be from Holbert, it's AJ Holbert and he looks at the fossil lipid composition of the mitochondrial membrane between different species and within species.

Jay (1h 24m 20s):

And when there's higher oxidizable, so higher amounts of unsaturated fats in there, it tends to be associated with aging and shorter lifespan. And so this, he's, he's come up with the, the membrane pacemaker theory of aging, which is basically, I would say kind of the next step beyond the reactive oxygen species theory of aging and oxidative stress theory, which is kind of building on the old theory, which is the rate of living theory and has shown that this can fully account for basically why certain animals that have a very high metabolic rate are actually not living as long. And when you control for PPH lipid composition, the animals, including humans that have the most saturated oxidized ability index of the PPH lipids tend to age slower and live longer relative to the opposite.

Jay (1h 25m 7s):

And he points to basically a handful of things. One is the susceptibility to oxidation and also an efficiency of respiration where the animals that have much higher amounts of the pie saturated fats and those membranes are not able to produce energy as efficiently because of the, both the proton leak and also their permeability to protons, but also potentially to sodium and potassium as well. And that leading to a state where an animal's much less efficient at converting the fuel that it's taking in into energy. And so it has to, it has a quote, higher metabolic rate, but it's really not because of elevated atp, but rather because it's not as efficient with the ability, the capacity to produce energy from that substrate. And so that's a piece of evidence, obviously not, not the only one, but I think does point to this connection here between slowing aging and extending lifespan and all of the diseases that come with aging being, at least in part related to fossil lipid composition and saturation index.

Jay (1h 26m 3s):

And yeah, the, the kind of other piece there is when you look within a species where the saturation index is normally constant as opposed to between species, the higher metabolic rate tends to win out. And, and that tends to be a sign that, again, it's not a matter of metabolic rate, but, and rather actually a higher metabolic rate, which tends to correlate with lower reactive oxygen species production tends to be the, the goal here as far as slowing aging and extending lifespan.

Dom (1h 26m 33s):

Yeah, I I believe that I, I don't think there's like a lot of evidence for these calorie restriction groups that it, you know, slowing your metabolism I think will lead to ultimately a faster demise. I don't think it's gonna prolong longevity and I think it's probably gonna impair your immune system over time. I know that the big study that was done in 2014 showed that like actually a, a little bit higher blood pressure and a higher body weight BMI was actually associated with longevity if you can make it to like 85 or 90 and, and having a, a relatively faster metabolism.

Dom (1h 27m 15s):

I'm coming up on my next meeting I gotta jump into, but, but I wanted to, a couple things I just wanted to mention, kind of clear about the ketogenic diet that quickly say that, you know, I'm a fan of the ketogenic diet in the context of a disease process, you know, and I'm a fan of kind of flexible dieting in the context of kind of eat whatever you want as long as you manage carbohydrates. But I, I do wanna make a statement that, because I think a lot of people talk about the ketogenic diet, the fad diet, that it's like, it's not a magical diet and I would actually argue that it is kind of a magical diet because the ketogenic, by changing your metabolic physiology, it fundamentally changes your brain energy metabolism.

Dom (1h 28m 4s):

But most importantly, it fundamentally changes the neuropharmacology of your brain. And, and it also has an objective biomarker that you can measure it by. No other diet that we know of can actually fundamentally change the neuropharmacology of your brain. And it's not doing it through a calories in, calories out situation. So it has nothing to do with creating calorie deficit. So from that content, and that's kind of what I study, like, you know, the, the neuroprotective anti-seizure, so I just kind of wanna throw that out there, is that there's very legitimate use of this diet for epilepsy because it's altering the neuropharmacology of your brain.

Dom (1h 28m 44s):

And I feel this has tremendous applications for neuropsychiatric disorders, specifically the field of metabolic psychiatry, which is something that I'm very passionate about. We didn't have time to talk about it now, but I just wanted to throw that out there, that it's a diet that is kind of magical in the way that it changes the neuropharmacology of your brain. And I think, you know, my research is kind of going in that, that direction.

Brian (1h 29m 11s):

Yeah, yeah, no, thanks for sharing that Dom. And, and if yeah, do, if you have to jump off and, and you you're up you're up against it. We can,

Dom (1h 29m 20s):

I do, Yeah,

Brian (1h 29m 21s):

That's, that's

Dom (1h 29m 22s):

Fine. It's a 90 minute cap, but I wanted to do two hours, but yeah, and I just wanna mention and plug, if you don't mind the keto nutrition website where we kind of hit various keto nutrition.org and also I'm a co-host for the Metabolic health Summit, so if you Google that, you'll come and we're in the planning stages of that. But I, you know, love this conversation between you, Brian and Jay. I think it was great and I think, and it helps to basically bring it back into like a voice of reason when it comes to come to different camps. I think we agree probably on more things that we then we disagree on. So I thought it was a great conversation.

Dom (1h 30m 3s):

Yeah, look forward to when it's out and I'll put it into our newsletter, the cater nutrition newsletter and share it around as much as possible.

Brian (1h 30m 10s):

Excellent. Well Don, well, we'll, we'll, we'll let you, we'll let you fly. Maybe Jay and I will finish up with some closing thoughts and Okay. And, but I appreciate you coming back on the podcast so

Dom (1h 30m 22s):

I'm glad to do a round two too if you wanna do that.

Brian (1h 30m 25s):


Dom (1h 30m 26s):

I just gotta jump to a meeting. Okay, I'd

Jay (1h 30m 28s):

Be happy to do that. It was nice talking with you

Dom (1h 30m 30s):

Don. Great seeing you Jay. Great talking with you Brian. Okay,

Brian (1h 30m 39s):

Good all Jay, it's just me and you now. Yeah, well I guess, you know, there was a few other things that we could touch on and then we can, we can close it up for everyone and maybe do a part two down the road with is, I guess let's come up with some action items for people. I think, you know, we talk a lot, you got, we got very in the weeds, not in the weeds, but know a lot of people probably don't understand 90% of stuff that was, so I think let's just bring it back to ground level and perhaps just give some actionable steps for people, you know, whether it's low carb, hard carb, whatever.

Brian (1h 31m 21s):

But what could people do to sort of, cuz I think one of the things that we should point out is doing any type of restrictive diet, you know, keto carnivore, a lot of the, the, the, the, the effects that, the positive effects that can come of it is the removal of these maybe gut stressors, these highly gosh, highly refined foods. Even the, the seed oil consumption is lowering those. So, you know, maybe those are the, the first items to discuss, but what, what some action items would you say maybe if he had a client come in and, and you know, instead of going like maybe the restrictive route, what, what route would you go?

Jay (1h 32m 4s):

Yeah, so, so I think you bring up a great point, which is where I think a lot of the benefit drives from in terms of ketogenic diet. And I know we kind of, kind of mentioned this in our discussion with Don, but it, I don't know if we ever really talked through it. I think he was saying on the gut side that he hadn't seen so many, so much to such as a clear impact or at least as far as what is being impacted in terms of the entire effect on the gut bacteria and gut microbiome, which I agree it's not fully parsed out, but I think there are some particular benefits where you see the increases in amania bacteria that amania musiny and the back, the para bacterias. And just wanna point this out because it'll circle back to part of my recommendation.

Jay (1h 32m 46s):

I know we're kind of going into the weeds a little bit, but, and, and there's evidence that just the effect of the ketogenic diet on the, on the microbiome is one of the major things that leads to its beneficial impacts. And just transplanting the bacteria from mice that were on a ketogenic diet to mice that were not achieved the same benefit. And I think you see this, you tend to see the same thing with calorie restriction and fasting as well. And so I think that is one of the major reasons why we're removing a lot of the harmful foods, whether it's through ketogenic diet or otherwise can be really helpful is through these effects on the gut and bring relief to gut health that was not necessarily optimal. And my preference would be instead of just removing all carbohydrates, removing any particular foods that you are either not digesting well or that are particularly hard to digest or contain a lot of the antinutrients and instead, you know, including foods that are well, well digested, don't have those antinutrients and I would say ideally that still contain carbs and that way we could get that benefit, that one benefit at least of, of the ketogenic diet.

Jay (1h 33m 44s):

I'm not saying it's the only thing necessarily, I think it's a huge one though, and but also the, the translation of then a reduction in endotoxin and lip polysaccharide being a big part of it. So what that would maybe look like for somebody who is just saying, all right, what do I do if I don't want to go full like restriction in terms of carbohydrates, you know, of course restriction's a tricky word because I think we wanna make different food choices and some, you know, we could perceive that as restriction, but at the very least I don't think it needs to be restriction of calories or carbohydrates, which tends to be much more difficult. But rather what I would say is let's remove I would say the, the biggest defenders in terms of issues with, with the gut. And so I would look to raw vegetables, at least raw leafy greens, especially, you know, some of the fruit vegetables like bell peppers and, and cucumbers aren't actually, well yeah, coersion would be, you

Brian (1h 34m 33s):

Know, removal of,

Jay (1h 34m 35s):

Well so yeah, removal the hard to digest one. So raw leafy greens, I wouldn't have raw spinach, which is super high in oxalates for example, or rock hale. I would remove raw nuts and seeds or really nuts and seeds altogether also because of their poof of content and the whole grains end generally the processed, most processed grains as well and shifting toward whole foods, shifting toward well cooked vegetables, fruits, well cooked roots and tubers, you know, potatoes, sweet potatoes, squashes, things like that. Which all tend to be digested much better. And I think that that can lead to a huge improvement. And of course an emphasis on on animal products as well. You know, good quality, low poof of seafood and, and meat I think and, and saturated fats being particularly helpful too from that

Brian (1h 35m 18s):

Standpoint. And do you have clients to take a, like a, a gut microbiome like test? Like any type of gut test?

Jay (1h 35m 27s):

I typically don't have them take them, but I've had quite a few clients come to me who have already had them. I think sometimes they can be helpful. I think sometimes they give us the wrong idea. Sometimes it, it leads to a bit of an alopathic approach where we just see a reduction in a certain type of bacteria and then we go and take a probiotic that has that bacteria or we see extra amounts of certain harmful ones and we, so we take something to reduce those. And I think for one, the microbiome is extremely complex and we are only under, you know, we only understand very small portions there. Yeah. And so I'm very hesitant to try to just replace the ones that are, that are low or and get rid of the ones that are too high, but rather would look to the things that tend to shape healthy microbiome.

Jay (1h 36m 9s):

And so for those things that would look to the polyphenols that are found in fruits and vegetables, those tend to have selective antimicrobial effects. So they tend to selectively kill off or reduce the growth of what are typically harmful bacteria and support the growth of ones that are typically beneficial. Again, that's the polyphenols and also some certain types of fibers in those fruits and vegetables that can be particularly helpful there. Having enough saturated fats to get good bio flow is super important for keeping our small intestine clear. So preventing sebo or helping to get rid of sibo, you know, having certain nutrients being very important for stomach acid production. So that's more of the ones I would look to is, is creating a healthy microbiome from the food as opposed to trying to artificially adjust a non-healthy microbiome that's only there is a product of our general state.

Jay (1h 36m 55s):

Now restoring healthy microbiome isn't always as easy as just eating healthy foods because if you're dealing with sebo let's say and you eat something that has a lot of fiber, which wouldn't be an issue for someone who doesn't have that or might not be, that could cause a lot of issues. You might be bloated and, and you know, feeling particularly bad, you know, brain fog and whatnot and skin issues and not from there. And so those are cases where we need to be very careful with our fiber intake and, and how we're adjusting the microbiome. We might need to use other tools, but those would be yeah, cases where it'd be, yeah, you might have to lean away from the more fibers foods and work on adjusting things more particularly using supplementation or or particular types of foods that might help more there.

Brian (1h 37m 39s):

And that could be sort of just like a self experimentation of, you know, you talk about like the ultimate elimination diet. I mean a lot of times people say carnivores like the ultimate elimination diet and some people maybe need to go that route to heal first perhaps, and then they can reintroduce other foods. Would you? Yeah,

Jay (1h 37m 58s):

Sometimes I would say maybe it doesn't have to go quite as far as carnivore, right? So even if you have some really bad gut issues, normally you'll be okay with some sugar sources, some carbohydrate sources, sometimes honey or maple syrup, sometimes those can cause issues but sometimes they're okay, sometimes really ripe fruits that are not too fibrous sometimes some fruit juice. So those might be ways to incorporate some carbohydrate sources that are still not going to aggravate a gut issue. And part of the reason why I think that's important is because having a high metabolic rate and the reflecting elevated T3 or a good thyroid state and not being in a hypothyroid state is really important for restoring healthy digestion, for good bio flow, for good stomach acid production and for good motility.

Jay (1h 38m 41s):

And if we don't have that good motility, that'll lead to overgrowth as well. So that would be my hesitation with just throwing out all carbohydrates is I would argue that that's gonna lead us toward that sort of state and that's gonna potentially lead to compromise digestion. So I would not necessarily recommend going full carnivore, but you might need to really quote, restrict what types of carbs you're eating at first while you're working on healing, whatever issues there are gut wise and then you should be able to incorporate more carbohydrates.

Brian (1h 39m 8s):

Yeah, and I, I don't know if you're a fan, I know you're a fan of like raw, raw dairy, raw milk, is that, or is that right? Is that something you incorporate?

Jay (1h 39m 15s):

Yeah, I think dairy can be great. Of course that's another example where, right, lactose intolerance is super common but it's also not permanent. So lactose tolerance can shift dramatically based on our gut bacteria, based on our thyroid function and enzyme activity. So T3 being the active thyroid hormone helps a lot with lactase production. Also, just not having anything with lactose for a long time will cause lactose intolerance and you have to kind of titrate back and and adjust back. So that can be a tricky one, but one that you can restore, you can restore your ability to consume dairy or to become lactose tolerant in the vast majority of cases. So yeah, I think dairy is a great one as far as a source of a lot of great vitamins and minerals, good saturated fats, some carbohydrates and some good protein as well.

Jay (1h 39m 55s):

But again, one that someone's going to have to evaluate individually as far as how well they tolerate it and how much they can have.

Brian (1h 40m 2s):

Well to finish up and then maybe we'll do another episode down the road. What, maybe explain to me like your, I know you and Mike have, I have a podcast energy balance podcast and I, I definitely been listened to a lot of it just I'm, I like to be an open book and learn about different ways of eating and I'm curious your routine, your eating, your workouts and things like that and how, how you manage it around your sort of bio point of view.

Jay (1h 40m 34s):

Sure. Where do you want me to start?

Brian (1h 40m 36s):

Well you know, for example, like how many meals, what do you typically, how do you typically structure those meals and, and then perhaps, you know, workout and things like that. Workouts, I'm curious. Yes,

Jay (1h 40m 50s):

I'll normally have three main meals normally with a snack or two or sometimes even three depending on how the timing lines up and how big the meals are. And a lot of it is, I would say not always optimal now just cuz cuz of travel. And so my availability for particular foods and being able to work out as we were talking about I think before we went live is sometimes hampered by the sacrifices with travel. But normally I would say I would be eating maybe three square meals and then sometimes a snack between lunch and dinner if that's, if there's a longer spread there or for whatever reason my lunch is pushed back, I might do a snack between breakfast and lunch and then normally I'll have a snack before but as well. And all of those meals tend to involve, tend to have a decent amount of carbohydrates and some protein and a decent amount of fat as well.

Jay (1h 41m 35s):

And yeah, most of that will be

Brian (1h 41m 39s):

In your carb sources are typically fruit?

Jay (1h 41m 42s):

Yeah, most of it will be centered around fruit, you know, dried fruit, fresh fruit, fruit juice, I'll do some, some starch as well. So potatoes, I like potato chips cooked in olive oil or coconut oil. I'll also do some corn tortillas with nix symbolized corn. So that's corn that's traditionally processed in a way that deactivates a lot of the antinutrients and improves nutrient availability. And that's the traditional way that's done through Latin American. So it's really easy to, to find corn tortillas that are nix mized. And yeah, so I'll do some searches like that throughout the day. And then normally with dinner I'll have some form of root vegetables, whether it's sweet potatoes, potatoes, sometimes white rice, things like that.

Jay (1h 42m 23s):

So that's, that's the main carb sources. Yeah, for the most part.

Brian (1h 42m 28s):

Okay. And yeah, is there anything else you wanna add? I mean perhaps we'll do another one and talk a little bit more about the Biogen lens and, and how you guys go about it. Cause it obviously is a little bit different. We've seen this shift to like, obviously that's why I wanna get you on in Mont is this shift to low-carb. And I've always been a proponent of fasting. I mean one of the, I know that, you know, you talk about how fasting obviously can put you in this stress stressful state. But the one thing I will say, and we can talk about this maybe on another time, is that I like about fasting, it sort of gives you a boundary throughout the day even, even if it's not like you're fasting half the day, but okay, I'm gonna stop eating at eight o'clock, you know, because I don't wanna be digesting food and going to sleep at the same time sort of thing.

Brian (1h 43m 14s):

And I think, I think fasting can be used from that standpoint where it gives you sort of these boundaries throughout the day. And maybe we can talk on that on another time, but go ahead. Yeah,

Jay (1h 43m 25s):

Yeah. I guess the question is what's the purpose of those boundaries? Is it to prevent overeating? Is it to prevent, as you said, eating too close to bed?

Brian (1h 43m 33s):

Yeah, I mean, because a lot of times what's happening when, when, when, when it gets later in the day, I feel like people sort of start eating worse foods, perhaps more processed foods and nothing really that beneficial to their health. So it can put boundaries around that.

Jay (1h 43m 49s):

It can, I think one thing thing I've seen a lot, obviously this isn't always the case, but yeah, one thing I've seen a lot with people who tend to really struggle with junk food or with processed foods and they feel like once they start they can't stop. It's a whole pint of ice cream like Dom said it, I'm not saying this is, this is his situation, but the, When people are struggling with with that state, I think a lot of times it comes down to undereating earlier in the day and probably not getting enough carbohydrates in. And there are, in terms of hunger regulation, there's a ton of different signals. One of the major ones, I would say the kind of most, the one that's most deeply, that we're most deeply attuned to that is going to be prioritized over any other is the energy levels, the ATP levels in our liver and in our hypothalamus.

Jay (1h 44m 36s):

And so if we're not supplying those areas with assuming eating carbohydrates with the carbohydrate enough carbohydrates, there's going to be constant hunger signals. And if we're also eating polys saturated fats and whatever else, it doesn't matter if we keep eating. Because if we're not efficiently, efficiently converting that to energy, we're gonna be still stuck in that generalized low energy state that's causing this constant hunger. And so there's some great papers talking about overeating being the consequence of, of the state of inefficient respiration. So our hunger signals aren't actually turning off and our bodies are giving us the right signal. They're saying we need more energy, but they're not efficiently converting the food that's coming into energy due to whether it's issues, pfa, nutrient deficiencies, excessive stress for other, you know, other reasons.

Jay (1h 45m 17s):

And so that's where I would look. And so in people who I've worked with where they felt like they had to be really careful with certain junk foods or processed foods cause they couldn't control themselves or they tended to over eat them at night when they just, I, I tend to suggest front loading in that case, and I don't actually mean putting all of your calories in the beginning of the day, but for most people they're so low on food earlier in the day. And especially with carbohydrates that if you just get the idea more so front loading, I really think it should be nearly even. But if you get into that idea, that mindset and you start to eat some solid meals earlier in the day, solid breakfast, solid lunch, and getting enough carbs in the responses that I've, I've heard from people are just astounding. Like they're so surprised that before when they, they couldn't have junk food in the house.

Jay (1h 46m 0s):

Cuz again, if they had a body of the ice cream, the whole tub was gone and more, and now they'll eat a third of it or eat a bit of it and put it back and it just completely changes that relationship with food. But again, I think this is coming from a place of actually fueling ourselves efficiently and not putting ourselves in a stress state where our bodies are starving for, for fuel intake.

Brian (1h 46m 20s):

Yeah, and no, that's a good point. And I'll just say like from my standpoint and when I was talking to Brad Kerns about, we did an episode just not that long ago and it just came out on his podcast in our mind is I took a dxa, I did blood work and what else did I do? Oh, the, the gene snip all this stuff. And I was like, okay, I'm gonna shift a little bit more into like the Biogen lens and, and implement, you know, now I used to never have anything in, in the morning. Now I'm having like fruit in the morning. And so it's, it's definitely been an adjustment. I will be, I will say I will be, I am going to the bathroom more. That could be,

Jay (1h 46m 59s):

Yeah, hopefully not too much, but I I know that,

Brian (1h 47m 1s):

Yeah, go ahead. Yeah,

Jay (1h 47m 2s):

Well I, I know like slow motility and constipation is super common in people not, you know, on carnivore not eating a lot of carbs, at least people I've worked with.

Brian (1h 47m 10s):

Yeah, yeah. And now I'm going and it's fine, you know, I just, yeah, there's definitely an adjustment and I tried to sort of slow my way into adding in more carbs and I, and one thing I tell people is it is good to track, at least in the beginning, just to see where you're at. Cause I think I realized that was probably undereating and undereating protein as well. And, and so, and my carbs were obviously lower less than like 50, I'd say on average, you know, for a while now it's like I'll have carb counts of upwards of 200, which is fine. I, I think my body's starting to adjust and so I'm sort of just doing this self experimentation and I'll go back and maybe four, six months and do adex and do blood work and see how things play out.

Jay (1h 47m 51s):

Yeah, I'm, I'm curious to hear about it. I did, I did listen to that episode. So you'll, you'll have to keep me posted. I, I, you know, I love hearing those conversations and discussion of, of these ideas and yeah, it's, I would agree that we would want to ease and slow, slowly tweak up to carbon take both because of carbon metabolism perspectives and also digestions perspectives and, you know, upregulating the enzymes that are gonna help to break those things down. Shifting the microbiome. I mean, there's, I would say it's important to go slow. There's a lot of, you know, ways where it can go potentially sideways. And so yeah, being careful and seeing how you respond and tweaking and adjusting. Yeah.

Brian (1h 48m 26s):

Yeah. And so we'll see that I, I, I always tell people that that's a good place for everyone to, to, to sort of start is like, you know, maybe to get a dexa or, you know, take some measurements and just get a feel for where you're at. And then if you're gonna make a change one way or the other, this way at least you have a little bit of just ev I guess evidence or something to sort of back up. But a lot of times it's how, you know, in the long run, how are you feeling? How are you know, I'm, I'm my, how are your workouts and how's your sleep? And things like that.

Jay (1h 48m 57s):

Yeah, yeah, definitely. And I know those were things that were dramatically different for me when I went from the lower carb fasting, keto side of things to incorporating carbs, like really night and day for me. And one of the night and day things too was the feeling of constant restriction, constantly looking at the clock as to when I could get my next meal in feeling like I was just not, you know, always having the carb cravings and then also as you were saying, how that translated to other things, how I was feeling throughout the day. And yeah, made a huge difference for

Brian (1h 49m 26s):

Me and, and, and will end on this and, and on this. But I, I am curious, I know, you know, like for example, I mentioned in the podcast that I, I have some genes that show that I don't metabolize saturated fat as well as maybe some other people. So it is interesting to see that maybe some people do do better, obviously on, you know, like I just had another car a on, it's not published yet, and how he, he's been doing it and, and feels great and has good numbers, you know, so it's, I don't know, it's, it's sort of a, I think it's a, it's just an individual thing to some degree perhaps.

Jay (1h 50m 2s):

Yeah, I think there's individuality. I think, yeah,

Brian (1h 50m 5s):


Jay (1h 50m 6s):

Think we've, and this is normal, but I think the whole industry or the whole, you know, everyone shifts one side or the other. So we went from saturated fat as evil to sugar is evil, so, you know, lots of carbs, low fat to no carbs. And I think there is a, and not that I think that it's always the middle ground necessarily that like moderation is key. I'm not saying that, but I do think we swung too far on one side, and we took this idea, this notion that saturated fat led to elevated cholesterol, elevated ldl, and that no longer being the case. And that's just a symptom. And we don't blame the firemen for, for the fire yet. Then we've, I think we've done the same thing with blood sugar and, and carbon take and looking at insulin resistance and diabetes and saying, Oh, elevated glucose, elevated insulin.

Jay (1h 50m 46s):

Those, those things must be positive in this state. We've, we're really making the same mistake that we have criticized others for making as far as the cholesterol hypothesis goes. And so I think, yeah, I think that's part of, you know, that's something that's happening. But yeah, there's certainly individuality. I'm sure that some people are particularly better on one side or the other. And I think there also, I don't think that we should ignore that, but I also don't think that that doesn't mean that there's certain physiological principles that are truths throughout. And potentially we can change, maybe not for us, maybe for the next generation around from there, how well we oxidize fats or carbs or how tolerant we are to those things through various epigenetic changes, genetic changes, you know, So I, I think yes, there's individuality.

Jay (1h 51m 32s):

I think there are also certain principles that are universal. And I think the ideas that we would want to shift not only us as individuals, but the entire human species to toward better improved complexity and function as opposed to the other way. And,

Brian (1h 51m 47s):

And you, and you make an interesting point, and then we'll, we'll shut it, we'll shut it down, but ancestrally, what was done was looked, is, has been looked at now a, a lot in, in a lens. And it's like, yes, was what, you know, there's some things that we can take from that, but is that optimal? Right? Like they were putting conditions that we're not in anymore. Right? So does that lead to optimal health? And I think that's a, you know,

Jay (1h 52m 16s):

Yeah. And we, I think, I think that's absolutely an important line of questioning. Right? Right. Is semi starvation occasionally helpful? Is occasional famine helpful? Is a lack of constantly available food helpful? Right. I mean, we don't orient our whole lives toward what was happening then. We recognize that gyms are really helpful and having a thermostat is, is helpful and, and there's a lot of things that we do that are nowhere near what was naturally done then. I mean, when we look at, even, even if we're on the low carb side and we're using MCT oil or olive oil from the other side of the world, I mean, yeah, there's, I think there's a lot of questions to be had there. And yes, a, I think there's question as to how much carbohydrate there was available. I think that there is more than is often cited.

Jay (1h 52m 57s):

Denise Mider has a great article about how ancient fruit is not free of sugar, super lone sugar and all fiber, like a lot of people point to. And so I think that we would've had fruit availability and some people say, Hey, if you're in a, if you're in, you know, Canada or Northern Latitude, how would you have had fruit? Well, if you look at the millions of years of our evolution, the vast majority was in largely tropical areas that would've had fruit near the year round, if not year round. If we look at, as I was saying, you know, mentioned the Bonobos, if we look at where they currently live, which is, you know, in a lot of the areas that we spent a lot of time throughout our evolution, they're eating almost all fruit. So I think carbohydrate availability probably would've been pretty decent, but I think it's even better now. And maybe that's an opportunity for us to be able to improve even further on, on what there already has been.

Brian (1h 53m 43s):

Awesome. Well that was good way to, good place to end it. Jay, Thanks for coming on. This was, you know, the longest podcast I've done, so, and, and the first one with an earthquake, so

Jay (1h 53m 56s):

It was also the first way with an earthquake for me, for sure. Yeah. Thank you for having me on. You know, I want to thank Dom as well and I'd be happy to further discussion. Do a part two, you know, dig into any, I know we jumped around through a lot of different topics and I don't know. Yeah, I don't know kind of how that went, but anyway, I'd be happy to, to jump in further, so,

Brian (1h 54m 15s):

Awesome, awesome. And best place to find you, Jay Feldman Wellness, right?

Jay (1h 54m 20s):

Yeah, so my website is jay feldman wellness.com and my podcast is the Energy Balance Podcast. And for anyone who is, you know, you were saying for someone who maybe isn't as interested in all the in depth mechanisms, but wants to have some takeaways as far as what to do, you know, as far as nutrition, how, how to address macronutrient intake, how do we adjust our exercise intake with the idea that we want to be increasing our, our cellular energy availability, the idea that increasing our metabolism is conducive toward improving our health. So yeah, if somebody is looking for some information there, I have a three seven day minicourse that goes through a lot of the, that information, a lot of those topics, and that can be found@jayfeldmanwellness.com slash energy.

Brian (1h 55m 2s):

Perfect. And I'll put a link in in the show notes for that. So, All right, Jay, thanks for coming on.

Jay (1h 55m 8s):

Yeah, Brian, thanks for having me.

Brian (1h 55m 12s):

Thanks for listening to the Get Lean E Clean podcast. I understand there are millions of other podcasts out there and you've chosen to listen to mine and I appreciate that. Check out the show notes@briangrin.com for everything that was mentioned in this episode. Feel free to subscribe to the podcast and share it with a friend or family member that's looking to get their body back to what it once was. Thanks again and have a great day.

Dr. Dom D'Agostino and Jay Feldman

Dominic D’Agostino, Ph.D., has maintained involvement in a vast array of professional, academic and personal endeavors. As an Associate Professor with tenure at the University of South Florida, Dom teaches students of the Morsani College of Medicine and the Department of Molecular Pharmacology and Physiology, with a focus on such topics as neuropharmacology, medical biochemistry, physiology, neuroscience, and neuropharmacology. He is also a Research Scientist at the Institute for Human and Machine Cognition (IHMC) to assist with their efforts towards optimizing the safety, health and resilience of the warfighter and astronaut.

Jay Feldman is a health coach, independent health researcher, and host of the Energy Balance podcast. He has degrees in neuroscience and exercise physiology and is devoted to using his knowledge and experience to help people heal from all manner of disease, dysfunction, and difficulty losing excess body fat



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