Geoff

Professor Ben Bikman, great to have you on the program.

Benjamin B.

Hey, Geoffrey, thanks so much for the invitation. I'm delighted.

Geoff

I think there's a lot of ways we could go on about the conversation here. Obviously, you're well-known researcher in the field of ketosis, ketones, all things low-carb, and all of that. And I think, one of the ways that I want to just start off the conversation is that, I see is one of the most prolific communicators on Twitter posting science papers, and communicating to sort of the average population. And perhaps, the way I start it off is, what do you think the role of social media is in this new role of academic research? And why have you adopted that channel as a communication platform?

Benjamin B.

That's a great question. And it's relevant because I was increasingly frustrated, especially as a scientist who was studying something that people cared about. It is relevant that it's my great fortune to study something that people care about. I'm in a hallway at BYU of scientists who study really neat stuff, but not a lot of people care. You know about much of what life scientists study. And through just a series of fortunate accidents in a way, my research interests focused more and more on insulin and insulin resistance. And mind you, it's kind of funny the way you mentioned that I'm, sort of, a ketone scientist. Even that is because I still I'm really at my heart an insulin guy, and that the two are so connected that it was just a logical progression for me and my research interests to get into that realm of ketones. But again, the foundation was and always has been my interest in insulin, and its relevance in disease, in the origins of most chronic non-infectious diseases. But specifically to your question, with regards to social media, my good fortune to study something that most people care about, and yet within academia, so much of what we publish stays in the small little, very insular world. I'll publish a paper, the only one who ever sees it is these 10 other scientists, and I'm the only one who ever sees their stuff.

Geoff

Right.

Benjamin B.

And we go to an academic meeting and give a talk, and it's generally the same people just nodding along to the same kind of information we already generally know about. And I thought, the more I would go and give a talk somewhere, whether it was a grand rounds talk at a clinic, or hospital, or whether it was to a public, like a Rotary Club, within a nearby city, or something, people cared about this. And I thought, how can I share this outside of the conventional methods, outside of my own classroom, or outside of my own manuscripts? So social media, of course, was the low hanging fruit. And my aim there became not to promote my own ideas, but to objectively share the most relevant research in real time as a paper would get published if it seemed to be relevant in this metabolic insulin, ketone context, that so many people care about, and that I care about as a scientist, I thought this is an easy way to share it. So sharing a little, kind of, snapshot of the abstract, often with some sort of one or two sentence description of the study to make it very palatable for the user or the person who would see it, that became something I was interested in, and have continued to do. So really, it was just a method to disseminate the latest most relevant research, just so people can stay informed, frankly, and not feel like they have to devote time on PubMed or Google Scholar every day, and finding these things on their own.

Geoff

I think one of the most important pillars of academics is, how do you communicate this in a way that's practical for normal people? Because a lot of the funding bodies are government funded, or military funded, or nonprofit funded, and that requires buy in and momentum from everyday people. Otherwise, we don't want to be in a world academics are just some scholars in an ivory tower that are not doing some real stuff. And I think that's kind of the critique from folks that don't quite understand what valuable work researchers are working on. But I also see on Twitter, and you've probably have seen this on ancillary to the low-carb ketogenic diet versus, the carb diet. I guess it's a calories in calories out folks, versus the metabolic advantage of ketosis folks. It's also that dark side of social media, where there's almost a holy religious war of ... Is keto the best thing ever, is keto the worst thing ever? I'm curious to get your take on the polarization side of social media, and how that's impacted ...? Or does that impact how you think about science communication?

Benjamin B.

It is relevant to note that they're, even within this few minutes of conversation we talked about, there is that lurking kind of war in a way, hopefully, it's not a war, but certainly a war of words in a way. But they're the sentiment that the metabolic plagues of society, obesity being the obvious aspect of that, is it purely a function of calories in calories out? This kind of perfect thermodynamic model. And then there's others who would say, "Well, no, it's an endocrine, it's a hormone-driven model." And mind you the ketone, I would summit the ketone aspect falls under that. To me, my very first step into a non-academic meeting was speaking at Low Carb Breckenridge two years ago. And it was to touch on that very topic, which is that ... My sentiment is that the endocrine model of obesity actually incorporates the thermodynamic model of obesity in so far as ... Especially relevant with David Ludwig's paper, just published a couple weeks ago, when you put a human into a condition where insulin is low, which would also mean ketones are high, that's going to be consequence of low insulin, you're increasing metabolic rate, and that's what David Ludwig's papers showed.

And Kevin Hall's paper showed that too oddly a couple years ago, that the humans in ketosis had significantly higher metabolic rate. And my labs research over the past two years, we've just been waiting to publish this until we had more human data, but we have data from adipose cells, we have data from rodents, and now from humans, where we're taking abdominal subcutaneous fat biopsies of humans in and out ketosis. The ketones are stimulating the metabolic rate in fat tissue. So the fact there is, when we try to balance how can the endocrine theory ... I mean, how can I be justified in saying the endocrine theory of obesity is that hormones control fuel used and thus have a strong handle, basically, control the levers levels of obesity, that encompasses the caloric, or thermodynamic model, because we introduce a new aspect of calorie expenditure. In fact, when you're in ketosis, I would submit, you introduced two new aspects of caloric expenditure, in that if ketones are elevated, you're one, increasing metabolic rate by enhancing what's called mitochondrial uncoupling in the adipose cells. And that's fascinating. We can talk about that if you'd like, and you understand it. But you increase uncoupling, which means that the cell is basically wasting energy as heat, which sounds bad, but it's favorable when it comes to body weight control. But then you also have the literal wasting of energy in the form of ketone derivatives that are exhaled, or urinated, or even eliminated through sweat in the form of acetone.

Geoff

Acetone, right.

Benjamin B.

Yeah. You have this explicit elimination, and someone would say, "Well, so what if you're breathing out, or urinating, or sweating out acetone." Well, the so what is, where did that acetone come from? It came from fat. We're literally cleaving the fat molecule into little pieces through the process of beta-oxidation. In fact, it's happening so much when insulin is low. Fat oxidation or fat burning is so high that we almost are burning more fat than we need. If you think about energy, we should only be breaking down molecules. Our catabolism should only be matched energetically speaking with how much ATP we need.

Geoff

Right.

Benjamin B.

How much energy does the cell need to get the job done? All right, we need this much energy, so let's break down that much nutrient to get it. But in the case of low insulin, we just keep burning through the fat, and yet we've reached our ATP target, and so you could ... I submit the extra is the body saying, "Well, we're burning more fat than we need, so we're going to turn the access into ketones because we have a way to get rid of it. And so we're literally breathing out these little pieces of a fat molecule. And mind you, that doesn't account for a lot of energy, but it's still energy that must be considered, if the caloric proponents are so staunchly not giving any ground. That's fine. Let's just say, "Okay, the middle ground then is that, we need to account for these two other methods of energy loss when hormones are, what I would say, in a state favorable to fat loss which is low insulin essentially. The increased metabolic rate from mitochondrial uncoupling, and adipocytes, and the acetone loss, which those are carbons that we're losing, that could have been used as energy.

We're not talking like carbon dioxide, which is the spent sign of energy if you will. But they had the potential to be energy because they could have gone to acetone, or could have gone to beta-hydroxybutyrate. And then all it would have been if it was beta-hydroxybutyrate, one step back to the pseudo acetate, now you've got energy again that you can burn. So, anyway, for me, it's not me trying to be diplomatic, it's me reconciling my own findings as a PhD in bio energetics, which is the study of energy and neo organism. And then this growing appreciation for the human evidence, especially, that finds that if you're controlling insulin, you really do seem to have this flexibility with calories, where you can have someone whose put on a diet, and this is ... Multiple papers show this. They split the people up, you're on a calorie restricted low-fat diet, you're on a calorie unrestricted low-carb diet, and these people still lose more weight, despite eating potentially 200 or 300 more calories a day. And that matters.

Geoff

We touched on a lot of different topics there. I want to talk about the metabolic advantage. I want to talk about mitochondrial uncoupling and acetone loss. And I think when people think about those subjects, I think they talk about it in this context of metabolic advantage. I want to unpack that a little bit, because I think from a weight management perspective, mitochondrial uncoupling, seems we've favorable. But I think on performance perspective, do you want to be lose energy?

Benjamin B.

Yes, exactly.

Geoff

And I think that's an interesting discussion to talking about.

Benjamin B.

Because people always want to talk about, "Hey, take this product, then it helps your mitochondria be more efficient." You literally will hear that in the advertisement. And I'm thinking, well, if you want weight loss, that's the last thing you want. You actually don't want your mitochondria to be efficient, because if your mitochondria in your fat cells, let's say, are perfectly efficient, they will go back to that idea. They will only use as much energy as they need. So they're never going be use any more. But if you have your adipocytes, your fat cells are inefficient, like I'm proposing happens in the evidence supports the ketones are inducing, well then you're burning through energy like gangbusters, and you're just wasting it as heat, which is fine, that means increased metabolic rate. But to your question, our data shows that the uncoupling that ketones induce in adipocytes, it does not happen in myocytes and muscle tissue. And we have this from isolated muscle cell cultures and rodents. In fact, we published this earlier this year, we found that there was no change. In fact, if anything, the ATP production for every unit of oxygen used went up this P:O ratio, that production of ATP per unit oxygen consumed went up as the muscle cell was fueled with beta-hydroxybutyrate. And when we insulted the muscle cells with molecules, just to induce some kind of muscle cell damage, they were actually more resistant to damage, and survived better in the midst of this noxious stimulus. So what appears to happen, at least energetically at the adipocyte, does not happen in the muscle cell. And in the muscle cell, you in fact do have greater efficiency, whereas in contrast, in the adipocyte you have this inefficiency. So metabolically speaking and performance wise, it's a perfect situation.

Geoff

Yeah. I think that's a level that I think a lot of people don't get the nuance. I think you explained it quite well there. Then when I think about metabolic advantage, I oftentimes think about, if you remember ... I believe the Veech paper, and I think '96 showing that you increase the electron span between site one and site three of the electron transport chain, burning PHP vs glucose. And there was ... So they increased delta G of burning ATP, as more the more primal ways of how you could talk about metabolic advantage. So I'm curious, when people bandy about that term. What notions do you think about? What do you think are the dominant characteristics here? I mean, I think it was instant result that you said that you see mitochondrial uncoupling in adipose tissues but in myocyte, which is kind of cool explanation of why you see enhanced performance, and also enhance a weight loss, where is that, oh, you're just burning energy, or wasting energy, but that which could be used for a performance case.

Benjamin B.

For me, I use the term of metabolic advantage to someone being in ketosis, what you just mentioned. Specifically the idea that, to me, it's an advantage, that you have calorically speaking, where you don't have to ensure, all right, I eat 1600 calories today. And as long as I expend more than 1600, and I'm going to be losing weight. What a horrible way to live. I don't know anyone who keeps that up long term. Calorie counting is tedious to the point of insanity. So, for me, the metabolic advantage, when I use that term, I state that in the sense that I mentioned, and you've mentioned, which is, you don't have to be counting every calorie you're getting in because you have this wiggle room. You have this ability to be a little more liberal into truly just eat until you're full as has been done in human clinical studies. I'm not making that up. They just tell them eat as much as you want, just restrict your carbohydrates. That's what they've been told. I can think of three manuscripts at the top of my head, where that was the explicit instructions. And the low-carb ad libitum eaters outperformed metabolically the calorie restricted low-fat eaters. That to me, is a metabolic advantage.

Geoff

I feel like when you actually dive into the literature of someone like Kevin Hall at NIH pub, who I would say is more in the school of calories in calories out. I feel there is some middle ground that people ... all could agree on. But I feel on the Twitter's sphere it is very polarized, can we still man the calorie in and calorie out arguments? I think you mentioned Kevin Hall's paper a couple years ago. I think he saw a modest increase in metabolic rate. But for some reason, he kind of hand wave that away, as saying, "Oh, it's not significant, and therefore calories are dominant. And this keto stories is not super compelling.

Benjamin B.

I don't mind that he or anyone came to the conclusion. But can we still man that argument. In a way, I think we can say, I'm comfortable saying calories matter, insofar as, this is energy that must be accounted for, and there's no getting away from it. And my simple position is that, in hormones, it would be adding this. And hormones drive caloric use. In other words, hormones dictate how the body uses energy, is it storing it, or is it expending it? And if it's expending it, are we considering all of the ways that it's expended? The uncoupling which would mind you be ... that would be encompassed in someone measuring metabolic rate, and I would contend that any study that has shown increased metabolic rate and low insulin states, it's probably through this adipocytes uncoupling. And then also making sure we account for the wasted acetone, which again is breath, urine and sweat. But this goes beyond David Ludwig's and Kevin Hall's papers. My initial interest in pursuing this hypothesis of insulin versus ketones in all three metabolic rate through brown fat, was actually based on research from Jocelyn and Benedict. And so, we're talking a hundred years ago. These extensive studies in the type 1 diabetics, they would see metabolic rate would be remarkably high in type 1 diabetics that were untreated, and what happens when insulin therapy was used. And this is in type 1 diabetics and in type 2 diabetics more recently, metabolic rate goes down.

Geoff

Crushes, yeah.

Benjamin B.

And so, to me-

Geoff

Interesting. It makes sense.

Benjamin B.

... it really fits. Exactly. I would see these papers, and I would think, could it be the ketones? And then I'd seen, I think it was one of Veeche's manuscripts in rodents, finding this enhancing coupling, and I thought, "Well, let's just kind of run with this idea, and see how deep it goes." And sure enough, we have it in all three levels, isolated cells, rodent adipose, and human adipose, increased expression of uncoupling, and mitochondrial biogenesis related genes, likely due to this reduced insulin. That's part of it. And of course, powerfully the increased ketones. But you can't eliminate the insulin from this. We want to say, "Well, it's just the increase ketones." And until someone does a study whether increasing insulin, and giving them a ketone, like a ketone ester, we can't say that it's just a ketone, because whether-

Geoff

But you can't unpack yet?

Benjamin B.

You can, yeah.

Geoff

It's deflated, right? It's ketogenic, it's like your eating ketogenic diet. So it's just like, okay, basically, you're forcing high ketones low insulin at the same time. But can we play it the opposite, or can we play it both at the same time?

Benjamin B.

That may be a question to ask with the kind of birth of this widespread use of exogenous ketones, that may allow us to tease that apart and say, "Well, are the effects of ketones just because of the ketones themselves, or does this have to happen in the state of load insulin? And frankly, I bet it without a doubt, insulin will inhibit those same genes that ketones are explicitly activating. And so, I think there was going to be some kind of moderate middle ground in that context.

Geoff

That in the sense I want people ask me, "Can you replace a ketogenic diet with the ketone ester? I was like, "There's going to be overlap on the indications that they can both treat." But there's also different effects, right, with a ketogenic diet. The carb restriction is probably even something that exogenous ketone, like a ketone ester is not doing, and vice versa.

Benjamin B.

Yeah. In fact, I would submit that I bet the most relevant, at least obvious application of that is going to be neurological disorders, where we have certain neurological disorders that are linked to a glucose hypometabolism, whether that's a result of insulin resistance or not, and to a degree probably is. But then your arms as you know, and listeners entirely know too, there are two fuel sources, it's glucose or ketones.

Geoff

Well, that's smart. And you can also lactate in some other things.

Benjamin B.

Yes, that's true. Yes, that's true.

Geoff

But, yes, I agree. The two dorminal ones are glucose and ketones.

Benjamin B.

When someone in a low carb state, or they're taking ketones, let's say, they're not low-carb, but they're suddenly introducing this other fuel, well, now the brain actually can use a fuel that maybe, if they aren't able to restrict their diet to that degree, to put themselves into ketosis through ketogenesis, that's an obvious application even if they aren't low carb to the point of ketosis. I would submit the most obvious relevance of an exogenous ketone is the neurological benefit. And who knows what else?

Geoff

Yeah. And that's something we hope to explore. I want to get back to the diet debates. I think it is just an interesting and applicable to almost everyone. And I feel like perhaps one reason why some of the folks on the calorie in and calorie out side is that, if you're eating just 5000 calories of fat a day, you're probably not going to lose weight, right? So I think on the side of the keto crowd, or low-carb crowd, I think everyone reasonable would realize that, yeah, calories matter at some point. If you're just eating, 10,000 calories of fat a day, you're not going to lose weight because you've so much calorie intake. But I don't think anyone serious in the low-carb keto space would be arguing, you can eat ad infinitum of fat, and still lose weight, right?

Benjamin B.

I certainly wouldn't think that. Any of the people that I know, they even have kind of most staunch endocrine theory of obesity individuals. I don't know. There are probably are some who would say, you wouldn't. But man, that'd be hard for me to reconcile. But a part of me, there's this kind of itch my brain, wondering whether someone's looked at that already, and tried to force feed higher lipid. I don't know. I'm wondering whether there's similar University of Minnesota studies that did that. For some reason, it seems like someone did. But, nevertheless, yeah, my hope is that both sides are reasonable enough in a way. When you actually sit them down, and remove the kind of polarizing binary environment of Twitter, and you sit them down around a table, I think there's probably more common ground than not. I'd like to think.

Geoff

It feels that way, when you read the literature. It feels like they incorporate both. And perhaps the differences of how they weight the factors. They think calories matter more. They think the endocrine system matters. And I guess that's where the edge of science says, "Okay, let's tease out exactly weighting of these factors."

Benjamin B.

What I'd like to say is that ... what I hope is that there's this teeter-totter of theories, and no one is ever trying to force the one side down all the way. I myself lean more in favor of the endocrine theory, simply because I believe the endocrine theory encompasses the caloric thermodynamic theory. But that does mean I give credence to the thermodynamic model. I just think if we ignore the endocrine, then we're not considering a necessary aspect.

Geoff

I think you put it really nicely there. I'd love to get that idea and notion out there because I think there is ... just both aspects make a lot of sense, and how we can reconcile this. Right, its kind of quantum mechanics and relativity, how do we have this standard model of everything, perhaps of dietary nutrition? One thing that I've seen you post a lot about, and I think this will be interesting for a lot of our listeners who follow a ketogenic diet, or have been following carnivore diets, which has been a recent fad trend, we had a lot of most popular carnivores on our podcast recently is, does too much protein kick you out of ketosis?

Benjamin B.

Yeah.

Geoff

And I think that's when ... something that I think a lot of the folks in the community just debate about. Too much protein, you get gluconeogenesis, that raises sugar, You're going to get kicked out of ketosis. What's your opinion? What's your thought? What does the data tell us there?

Benjamin B.

So, in fact, I thought so much about that. That, that was the subject of one of the only other few talks I've ever given outside of academia. Because when I first started taking my steps into low-carbs and in ketones specifically, I was struck at how many people, I considered were eating in a very bizarre way. And I joke, but it was based on real people I knew. Or they were basically in a day eating almost nothing but MCT oil, because they were so determined to stay in ketosis. And I thought, what a bizarre way of eating, when people are just drinking oil. And I thought that's not healthy, and it's someone who's chasing ketones. And they were doing that because of their fear of protein in this idea, that protein will kick them out of ketosis. It's so important to just appreciate the very basic biochemistry which I believe is rational in a way. That it's quite pretty easy for people to not along too. But gluconeogenesis, or the process of the liver taking carbons and turning them into glucose, that's not demand-driven. If it were, you could have someone who's taking away protein shake, and they would become dangerously hyperglycemic, and have this potential of a hyper osmotic glucose to urea, where the glucose is so high for so much, 220 milligrams per deciliter and above for so long. Then now it's fully-

Geoff

So you mean supply-driven?

Benjamin B.

Supply-driven. I'm sorry. That's right, yes. Yeah. You can push the gluconeogenesis into this hyperglycemic range. So, that's one aspect of this. My contention that there's no need to fear protein. And in addition to that, if someone is activating gluconeogenesis, you can't afford to have a substantial increase in insulin, because insulin inhibits gluconeogenesis. And so, the two ideas are in opposition to one another. If someone's taking protein, you can say, "Well, it's either going to increase the insulin, or it's going to increase the gluconeogenesis." And they may say, "Well, wait those are the same." No they're not. If you're increasing insulin, you're inhibiting gluconeogenesis, the liver will potently smash down gluconeogenesis.

Geoff

Right, because insulin sucks down sugar, right?

Benjamin B.

Yeah. It doesn't want to create glucose and releasing it in the blood. It wants to tell the liver, and the muscle, and other tissues to pull the glucose in. It wants to lower blood glucose not increase blood glucose. So the way we reconcile all of this ... and, indeed, the data supported, I encourage anyone to look at old papers from Roger Unger and Dennis McGarry, to look at this, especially Roger Unger. If the person is taking a fairly large bolus of protein, like one gram per kilogram protein, if they're in a low-carb or fasted state, there's no significant increase in insulin, none. The insulin just hums along like normal. And that's because if they're in a low-carb or fasted state, they can't afford to stop gluconeogenesis. And so, even if the protein and some of it is used to create glucose, that's fine. Who cares? We need it. We do need glucose, not because the brain needs it, I'm not going to say that. But we know there are cells like erythrocytes, red blood cells, that rely on glucose to ... They have a non oxidative metabolism entirely.

And so, regardless of what cells may or may not need it, we have some that do need glucose. And still, thank heavens, that can happen. In fact, we need it. That if you're not eating it, good thing we can make it. And if there was a substantial bumping insulin for meeting protein, it would stop that process when the person faints, or goes unconscious from ... through genuine clinical hypoglycemia. So my response to that is, there is no need to fear protein. Someone should continue to eat real food, including meat, which is high in protein, of course. And they don't need to fear they might going to get kicked out of ketosis. And I think the keto carnivores are a good example. A lot of them post their pictures before and after with ketones, although many of them get to the point of not caring about that. But I've seen enough do it, they don't get kicked out of ketosis when they eat a steak. They're still very much in ketosis. In that much steak, Shaun Baker should be dying from hypoglycemia in amber. They should be dying from hypoglycemia. They're eating so much protein from their meat, and they're not only healthy, I would argue that they're quite remarkably healthy, frankly.

Geoff

Yeah, I mean-

Benjamin B.

So there's the answer. Someone has to consider what insulin is going to do to gluconeogenesis. And you can't afford to have this insulin spike if you are truly carbohydrate restricted in your diet, because you can't stop gluconeogenesis. And that means if insulin doesn't go up, because it doesn't want to inhibit gluconeogenesis, it also isn't able to inhibit ketogenesis, which is why if someone's on a ketogenic, low carb diet, the protein will not kick them out of ketosis.

Geoff

What do you think that mean came from? I guess perhaps when people are eating a mixed diet with some carb-

Benjamin B.

Definitely.

Geoff

... and some protein, then maybe you're accumulating-

Benjamin B.

Then you get-

Geoff

... a little of the carbon and protein load together just to keep you out of ketosis.

Benjamin B.

Yeah. And that is-

Geoff

But we're talking about just protein and fat.

Benjamin B.

That's right, yeah. It's forgivable for people to make that conclusion that, "Oh, proteins are always going to spike insulin inhibit ketogenesis." Because when you add protein to a carbohydrate meal, you do enhance, you do get that additive insulin spike. And so, I can see why we came to that conclusion in general. But we came to that conclusion, despite the evidence that existed from decades ago, refuted that idea, that if you're in fact-

Geoff

But that makes sense. That makes a lot of sense to me. Because I think when I've been wearing a continuous glucose monitor, I've just been thinking, I'll see mild sugar spikes when I'm eating meat, but I'm also realizing that I'm oftentimes when I'm doing that, eating some salad, I might have some little bit of carbs in there. So it's not a perfect experiment, just on a personal, and equals one, right?

Benjamin B.

Yeah, that's right. And even still, though. I wonder, did you ever measure ketones before and after, and see substantial change?

Geoff

When I was going on a carnivore diet I didn't go that deep into measuring blood ketones for some day.

Benjamin B.

Yeah, I usually people step away from it, yeah.

Geoff

I did a six-week block of doing twice a day, finger sticks, for six weeks on ketogenic diet. And I never went full carnivore on that same block. I was thinking about doing that again. But it just ends up being annoying, when you're traveling, and doing business. It's hard to just pull out meals and starving yourself when you're on a business dinner or something.

Benjamin B.

Oh, yeah.

Geoff

So what do you think of carnivore? I think that's been interesting in terms of a fat diet that has definitely cuts, the attention of some mainstream media, where people have been conflating it from a Silicon Valley Bro diet to something tied with the alt-right, right?

Benjamin B.

Yeah, yeah.

Geoff

We have Mikhaila Peterson on the podcast. And I know that her and her father, Jordan Peterson, have been big carnivores. And I think some people have tied Jordan Peterson to the alt-right, and made this whole weird shenanigan.

Benjamin B.

I'm fascinated by it. So, Jordan Peterson ... not to change the topic too wildly. I'm also from Alberta just like he is. He's from northern Alberta, I'm from southern Alberta, but same kind of small little town. It's so funny for me, because to me it's almost sort of a tough love of parenting. Everything he's ever said, I think that's what my dad told. And I was raised by a dad, and my mom died when we were all quite young. So it was very kind of dad heavy parental environment. And very loving wonderful father, but also just pragmatic to the point that everything Jordan Peterson has said, that to me, is just so intuitive, frankly, his lessons. But nevertheless, the fact that Jordan Peterson not only speaks such nuggets of wisdom, but is a carnivore, makes me think, hey, maybe there's something to it. Because Jordan Peterson he's no dope. And I suspect his daughter is neither. Anyway, to your question, explicitly, I'm fascinated by this rise of the carnivore diet. I'm fascinated by it. And what I appreciate about it is the simplicity. A part of me kind of envies just the true simplicity of such a diet, where you can just tell yourself, "I'm going to eat these things and nothing else." And I look at that and I think, that really does. I mean, if you can commit to that simple idea, it is in a way, just easier in a way than even a low carb-diet, because you're always ... with low-carb, you're always kind of flirting with the carbohydrates. You're flirting with them. And how much-

Geoff

A couple of knack carbs here, kinda squeeze by.

Benjamin B.

Yeah, yeah, exactly.

Geoff

Yeah. It is ...

Benjamin B.

Exactly. That's exactly it. That's for me, the main appeal is that. Not that I am an anti vegetable kind of guy, but I've really appreciated some of the sentiments that have been revealed and expressed in social media around that, and the relevance of vegetables. But I appreciate the simplicity of it, where there's just, "No question. This is what I'm eating." And so you'll eat it. It fascinates me.

Geoff

How about the fiber story, the vital nutrients story. Obviously, when you talk to carnivores, it's like, "Oh, maybe you don't need that much fiber. Maybe you'd actually don't want these vital nutrients. Maybe these are stimulated immune response actually."

Benjamin B.

To me, a lot of the discussion of fiber and even polyphenols are relevant to gut bacteria. That to me, is the obvious application, because they're used by gut bacteria, and the fibre. I think it's nonsense to think dietary fibre is necessary for bowel movements. I think that is laughably silly. To me, I think it's as a fuel for bacteria. And even then, you'd say, "Well, then, so what? What do we need them for?" To me, much of the benefit of bacteria, and now I'm not a gut bacteria guy. To me, it's just a big black box. And too many people speak with too much confidence about it. I get very skeptical because I don't think we really know too much.

Geoff

I agree. I think people make too broad claims on it, yeah.

Benjamin B.

What I will say is this, much of the benefit to me, and gut bacteria is the production of short chain fatty acids, that we have the butyrate in the propionate, for example, that we just really don't get in any other way except the gut bacteria making it. And then that gets moved into the bloodstream. And we know these short-chain fatty acids are very beneficial signaling molecules for mitochondrial biogenesis, and mind you, even uncoupling in fat cells. And so, to me, the polyphenols and the fiber, despite any other claims anyone makes, I like to think of it as those could be potential sources of short-chain fatty acids from the bacteria. But then even then, do we need those short-chain fatty acids? No, you do not need them. And could someone get the short-chain fatty acids in other ways? I actually deliberately drink a little bit of apple cider vinegar in water, because I like that acetate. And that's a short-chain fatty acid. Mind you, exogenous ketones are doing the same thing. In a way a pseudo acetate is basically a short-chain fatty acid. Mind you, it's slightly altered structure, but even exogenous ketones kind of check the same box, that to me, apple cider vinegar checks, and then it's the source of these short chain carbons that are going to basically activate these same processes. But in someone who's eating a conventional standard American diet, I would be vehemently say, "Eat fiber." To me, there's little question that's going to help. But if you're going carnivore, then maybe you just don't need it as much.

Geoff

You can get away with it.

Benjamin B.

Maybe, I don't know. And I'm going to say maybe, just because I only want to talk about science that I know is published. I hate making a claim, and I don't think there's any study on that

Geoff

I agree, I think let's be proper scientist. I think we can speculate, and give some hypothesis. But, yeah, I think it. Just on a charted territory, I think a lot of people are curious about. Again, I think hearing from you, how you speculate about some of these more untapped areas is interesting to hear.

Benjamin B.

Yeah.

Geoff

Another constant ... I think this is more of an open area of debate and discussion is constant ketosis or cyclical ketosis. Is there trade off benefits for one or the other? I think there's been some studies coming out of the Buck Institute, looking at cyclical ketogenic diets, have shown just as much improve longevity as constant ketosis. What are your thoughts there? Do you have a specific preference? I imagined this trade offs and benefit for both types of protocols.

Benjamin B.

I agree, I bet they're. I suspect whether there's a true benefit, probably depends on the context. In other words, what's the person going for? If this is a person who needs to control a neurological disorder, like seizures, or even migraines? In fact, I think the very first publication looking at ketosis and migraines was published in 1910. But to remarkable effect where ... The study in fact is quite fascinating, not to go off from a tangent, but the physician noted, I think 12 patients, and noted what happened from the moment they went into ketosis. And he actually adds this little note based with each subject. And it's fascinating to see it would be something like, "Had frequent migraines three times weekly for 10 years, experienced an immediate resolution upon entering ketosis, and has not had another since." This little blurb. And that's powerful stuff that you just don't really get in publications nowadays. And another one he said, "Had two migraines daily for 15 years, and has experienced three in the following six months, and has not had another one since." Something like that. I mean it's pretty powerful stuff. Nevertheless, back to my point, if someone's trying to control a neurological disorder like seizures, or say migraines, then I think I'd say, don't mess around. You just stay in ketosis because you're probably going to trigger an event the moment you get out. And that does seem to be the case, at least, for some. If someone's an athlete, then I don't know. I've kind of wavered on whether ... Like Zach Bitter, this really kind of paradigm athlete, should he be stepping in and out of ketosis?

I guess the fact of the matter is, I think he does train with some carbohydrate, and does exceptionally well. So I'd say for him and these maybe endurance athletes, maybe that helps, if someone is trying to really lose a lot of weight, I would argue, all that's going to happen and really bump up their insulin is they're going to stop fatty acid oxidation for some period of time, because that's what insulin does. However, I would say if someone if going to go in and take a glucose tolerance test in a clinic, they'll probably be well-served by doing a bit of cyclical ketosis with some carbs just to make sure they stay glucose tolerant. And having disclosed that, I worry that some people would say, "Well, wait a minute, that means they're also insulin resistant." Because so often, if you are glucose intolerant, that means you're insulin resistant. But I don't think that is the case in someone who's on a low-carb ketogenic diet. I think they do start to become somewhat less carb tolerant, at least for a period of time. But that's not the same as being insulin resistant. What I haven't seen, or if I have I've forgotten, put someone into ketosis through ketogenic diet, give them glucose. So often we just track the glucose, and yet it might take them longer to clear the glucose because they've kind of become glucose intolerant. But I bet their insulin doesn't go up nearly as high as the other person. And so it's the seaming kind of disconnect and uncoupling from insulin sensitivity and glucose tolerance where you can be insulin sensitive, and yet have induced this glucose intolerance state simply because of such a prolonged shift in fuel use. The person has been in such a fat burning mode for so long.

Geoff

All the enzymes shut down for glycolysis, and it's optimized for fat burning, yeah?

Benjamin B.

There's almost this method of saying, "Well, I'm not using this pathway, I'm using this pathway." And so, wait a minute, now we got to use this one. Not only are we using it, but you just drink up 50 freaking grams of pure glucose. I mean, that's more than a little bit of pure glucose coming right into the system. I would suspect that's enough ... I hate to use these kind of terms, but you can forgive me for it ... enough of a metabolic shock, that there is this glucose intolerance. And I would argue that's not bad. If the person's not eating glucose, they've just clearly switched their body to fat oxidation. Why mark around with maintaining anti-glycolytic processes when you're simply not using them. I submit that is not the same as insulin resistance. So when people want to say the ketogenic diet is causing insulin resistance, no, it's not. It's causing glucose intolerance. That's what the research shows. Those are not the same thing. And so, I think if someone actually has to go in, and they need to play the game of reaching typical clinical cut offs, you probably ought to start cycling in some glucose, maybe a week or two before, just to make sure you pass that test so your doctor doesn't freak out.

Geoff

Yeah. Interesting.

Benjamin B.

Or you just say, "To hell with the doctor," and you say, "I know what I'm doing." But I'm not an insulin physician, so that's not medically advice. I'm a scientist for heaven sakes. No one can listen to what I say in it. But I'm not a doctor, I'm not a physician.

Geoff

We're touching upon a lot nuanced aspects of ketogenic diet fasting, ketones, insulin, glucose, And I think there's one thing that I don't think a lot people are articulated, is that, when you're on a ketogenic diet or fasting for a long time, I've never heard this articulate in your way of where it's glucose intolerance versus insulin resistance. But people will say that cycling glucose after a long period of a ketogenic diet or fasting, there will be sort of insulin resistance because you're less good at pulling down sugar, because your enzymes and processor folks so highly on ketosis, in fact, oxidation. So your argument is that, it's not appropriate, and that's why you call that insulin resistance has increased, it's mainly a glucose intolerance, and you're going to have some adjustment period where glucose is going to be processed and broken down.

Benjamin B.

So when people say this is a physiological insulin resistance, in a way, I kind of resist that. I mean, I can see what they're saying, and I'm diplomatic enough to kind of nod along with that. But even still, a part of me as an insulin resistance scientist, who looks at insulin resistance as overwhelmingly a pathological event, I don't like to say carbohydrate restriction causes physiological insulin resistance. I would rather say it causes physiological glucose tolerance. And that may be semantics, but I would argue that's a better definition. But because there are actual states of physiological insulin resistance such as pregnancy and puberty, those are the two known identified states of physiological insulin resistance, where it's not pathological in origin. It's not a result of someone changing to an unhealthy diet. And it is, in fact, serving a genuine physiologic need, where with pregnancy and puberty, these are the two exaggerated states of human growth. This is growth at a level, at a stage, you just don't see at any other time of life, really, when a woman is actively growing the placenta and the fetus. That elevated level of insulin helps promote the growth. I mean, it's stimulating, not only lipid accumulation on the mom, so that she can have this energy reserved to be prepared to breastfeed, but also growing the tissue of the placenta, and physically providing this slightly hyperinsulinemic environment for the fetus to stimulate growth. And the same thing goes with puberty, where we're just stimulating this growth because insulin is a growth molecule, and it's assisting in the growth. So that to me, is true physiological insulin resistance when ... If we're physiological, that means it's serving a good purpose. At least, that's what we should mean in the case of saying ketogenic diet is physiological insulin resistance. I don't think it applies. I don't think it's the same thing. I would prefer that we all come to a consensus that I'm right. And that it should be called physiological glucose intolerance.

Geoff

This a good argument for that, right? Because with true insulin resistance, it's much harder to re-shift out of that state versus a temporary period of glucose intolerance.

Benjamin B.

That why I think that. I mean, it seems right. I mean, we're two rational guys, and we agree, so this must be right.

Geoff

It's kind of full circle here around insulin resistance, your core initial area of research. And it seems to be that idea that insulin resistance is such a core piece of so many diseases. You can make that argument that insulin resistance, it has huge implications in diabetes, neurological implications, we talked a little bit about glucose uptake disfunction, and case of Alzheimer's, for example, obesity, maybe some cancers have some relationship to insulin resistance.

Benjamin B.

Yes.

Geoff

And then you look at the historical case, where we've had to carry out on the program, and you hear that whole story of around, okay, you see sugar spike intake in society, and then you see all the modern diseases spike. Again, that's not necessarily a causation argument. But there's some smoke around there. And I've known ... some friends in Silicon Valley are saying that, "Insulin resistance is basically the root of all evil." Just curious to get your thought of it.

Benjamin B.

Yeah. So, oh, man, I'm just tickled you brought that up. So let me just provide some fun little context. So, here I am, during the course of my PhD with a wonderful PhD advisor at ECU, East Carolina, named Linus, an insulin resistance guy. Then I kept seeing his manuscripts getting published, and was so delighted to join his lab, and study the changes in insulin resistance pre and post gastric bypass. And even then, I moved into my postdoctoral fellowship at Duke, this collaborative Duke Medical School, actually in Singapore of all places. So I move my little family to Singapore, and I study with another incredible scientist named Scott Summers. Again, in the realm of insulin resistance, and in particularly, the biochemical causes. In this whole time, I'm thinking, really, the only relevance of insulin resistance is type 2 diabetes. And then obesity, my thought was, obesity is causing insulin resistance, which is causing type 2 diabetes. That was the paradigm. And I never even imagined there was any other directions and arrows here. And mind you, I've come to actually kind of flip those around a bit. But nevertheless, that's what I'm thinking. And then I get hired as a brand new assistant professor at BYU. So we leave Singapore, move back up into the mountains of Utah, which is great for skiing, mind you. And then, all of a sudden, I'm teaching a class. The task that my department of physiology department asks me to teach a class called, pathophysiology. And I'm thinking, "What on earth is pathophysiology." I had a lot of physiology background in the course of ... my PhD was a lot of physiology, and biochemistry, but almost all the context of metabolic diseases. But, nevertheless, I'm very familiar with physiology.

And so pathophysiology is the study of the physiological processes when they go wrong basically in the explanation and identification of diseases. And so the class is about 100 nursing and pre-med students. So here I'm about to teach a class, and they give me a semester to prepare. And I'm thinking, "I don't know what causes fatty liver disease. I don't know what causes heart disease. I know insulin resistance." And so, in an effort, as I was structuring the class, and I would go through neurological disorders. I would go through hepatic liver disorders, musculoskeletal disorders, all this kind of through the body, breaking down the most common diseases, and their physiological origins, or when things are going wrong, so pathophysiology. And I'm so desperate to try to speak as an authority on this, because at the time, I'm one lecture ahead of these kids. And that's the kind of unspoken truth in academia, at least when you start generally, you barely know more than your students at the beginning. And I'm so desperate to come across as an authority, that I would think, as I was preparing that first semester, I thought ... I'm preparing the neurological disorders lecture, for example. And I'm remembering some conference where someone talked about the link, how type 2 diabetics had significantly greater risk of dementia. And I thought, "Maybe I can talk a little bit about that." And so, I would look in some research there and be amazed. "Wow, there's a huge connection between insulin resistance and Alzheimer's disease. And then I'm looking at heart disease. And mind you, that connection is just overwhelmingly as strong. And same thing with fatty liver disease, same thing with musculoskeletal disorders, like osteoarthritis or muscle wasting. Same thing with infertility, whether it's ovaries or testes. There's a profound link between altered fertility functions and it's resistance. And it just kind of kept going.

And I was amazed and delighted, mind you, because at the end of each one of these different sections, I could do my liver section, and talk about liver diseases. And then get to the end, and talk about the most common liver disease, which is fatty liver disease, and say, "Hey, you know what, let's talk about some of the actual ideology, or the processes that cause this, and look at how relevant insulin is." And I found that I could kind of basically wrap up almost every one of these topics, do the kind of genuine pathophysiology text version of it. And then have it kind of wrap up my way, which is, say, hey, insulin resistance is highly relevant. And isn't that great news? Because we can do something about insulin resistance. It is so modifiable, so rapidly through lifestyle changes. And that started to really shape the way I appreciated what I once considered some very narrow disorder or insulin resistance that was only relevant to diabetes. And then suddenly finding that you can take the most common cancers, breast and prostate cancer, yet strong connection to insulin resistance, numerous neurological disorders, hepatic disorders, muscle, bone disorders, and seeing that most chronic diseases can be linked, at least, explicitly to insulin resistance or insulin resistance is exacerbating the condition, which is what I would usually say, with cancers, insulin resistance is not causing the prostate cancer, but it's probably making it worse. It's not causing the breast tumor. But when you think of the average breast tumor has seven times more insulin receptors than the normal breast tissue, that's pretty relevant. And so not only is it more sensitive to the anabolic signaling of the insulin, but hey, in the same situation, you're also often hyperglycemic, and what's fueled is cancer cells prefer the most, well, glucose.

Geoff

Glucose.

Benjamin B.

So you're stimulating the growth, and you're fueling the growth. Anyway, cancer is a pretty hot button item, we don't need to get stuck on that. But you can look at virtually every chronic disease, some aspect of it will be exacerbated, if it wasn't explicitly caused by insulin resistance. The good news of that is when you can take any of these seemingly separate disorders, someone is taking a hypertension medication, they're taking a hypoglycemic medication, they're taking migraine medication, whatever. When they just wonder, "Could all of this have a common metabolic origin with insulin resistance? I'm going to change my lifestyle to address my insulin resistance." I have seen this happen so often in people, friends and acquaintances, where they get off every one of their medications. I mean, four or five medications simply because they addressed the one root cause. That's good news for people. And that's one of the reasons I'm so interested to talk about it whenever I can. It's because I want people to know, you don't have to be looking at all these things as different diseases, they're not different trees, they're just branches off the same trunk.

Geoff

That's super exciting. And I know that there's interesting discussion around the role of statins, are they reasonable given if it's metabolic origin for cardiovascular disease? Is a lipid hypothesis for, again, with the statin treats, is that the right approach? And sometimes I catch myself thinking, are we just too in the cool light? Is the answers so simple, or if that you have one route ideology for all these conditions? I kind of want to pinch myself, be like, okay, what is a skeptical response here? Are we being too neat and too cute here by answering all the disease?

Benjamin B.

Right. In fact, It is so necessary to say that. I try to be honest enough with myself to ask myself the same question. And in fact, heart disease is a very relevant example. And mind you, there are people who could speak much more lucidly intelligently on that domain, like Ivor Cummins, has devoted much more time to that specific topic than I have. But even then, so, I would say insulin is in each of these disorders we've talked about, it is always relevant. But is it the only relevant disorder? No. Absolutely not. And some of them it is. If we take Polycystic Ovarian Syndrome, the most common form of female infertility, yeah, if you get rid of the insulin, as far as I've seen in the data, you are resolving the problem.

Geoff

Right.

Benjamin B.

You have absolutely corrected the imbalance, and androgens, and estrogens being produced from the ovaries when you've lowered the insulin. Now, with heart disease, or Atherosclerosis, is it purely insulin? No. I don't think anyone's going to say that. But I think a lot of us would say, if you're ignoring the insulin, you are ignoring what could be the most relevant variable, and if not the most, one of the most.

Geoff

When I took on this journey of going through the literature that's ... It had got me personally excited about a ketogenic diet and all of that, because you're like, "Oh, wow, I gotta change my lifestyle. Otherwise, I'm just going to die of all these diseases." But I want to still man the role of carbohydrate. It doesn't mean we should all use sugars all the time. But what do you think are the appropriate use cases of carbohydrates? So I know for a lot of our customers, and a lot of our listeners actually are also professional athletes or athletes trying to improve, and break PRs, and all of that, and glucose, unnecessary anaerobic fuel, a very potent readily available fuel. So given the context of longevity, and health, versus performance, is there just like a trade off there? And I think that might be part of the conversation. Are we optimizing for performance so he can win the Olympics, or you're trying to optimize for longevity and health span? I think there's one that I mentioned there. And then there's a dimension around is the way they cycle these things, or you use carb strategically, and then you use a kitchen at strategically, or using exogenous ketones strategically to maximize some objective function that matters for you specifically as an individual.

Benjamin B.

I agree with what you said. We really do need to just ask what is the goal? And I think we can agree that these modern day endurance events are really artificial. Frankly, I don't mean to insult anyone. I have nothing but massive respect for the people who do these. But they are very fake situations. I can say the same thing about my workouts. I'm not really much endurance guy, I'm much more of a calisthenic. I mean, why do I need to do muscle ups? That's pretty fake. But I would say maybe it's less fake. At least if I'm stuck in a pit, at least I have to do a muscle up to get over a fence or whatever.

Geoff

How many muscle ups are you doing in a set?

Benjamin B.

Oh, man, those are so hard.

Geoff

They're fun.

Benjamin B.

If I do them in the afternoon when I'm genuinely warmed up, I can do four. If I kip, I can add a couple more. Man, that's pretty humiliating though, because I always considered myself really good at pull ups. And then when I turned 40 a couple of years ago, I decided to stop weight lifting for awhile, and just do calisthenics, because I'd always wanted to do a freestanding handstand pushup, always, my whole life. And I thought, "I'm 40-years old. It's time to freaking do this thing." And I'm still trying. I can't keep the balance. But a part of that was also adopting other aspects, like trying to do a plunge, trying to do muscle ups, a back ... a front lever, anyway, anyway. So-

Geoff

Yeah. I distracted you there. I guess I was curious, because I like doing muscles by itself. I think it's a great exercise, yeah. But I think, yeah, we were talking about the role of carbohydrates, and how do we incorporate all this stuff and performance, and all of that.

Benjamin B.

Yeah. In endurance events, where we have people just running incredible races, and incredible events, I would say you probably do need some kind of carbohydrate. Then I think even the most Ketogenic of these athletes, like let's take Zack Bitter, for example, who just broke the world record for the 100 mile run. He's taking carbohydrate during his event, and he's even taking some of it while he's training. And he's very, very honest about what he takes and what he does. But he's also decidedly a low carbohydrate ketogenic kinda guy. And again, I would argue, those are very artificial situations where you're creating a need that might not be real. You know what I mean? Does that make sense? And so, if we're talking about these remarkable feats of human performance, yeah, we probably have created a need for carbohydrate, because we've have a created-

Geoff

I see your argument.

Benjamin B.

... a situation. In the context of, does someone need carbohydrate for longevity? I would absolutely say no. And that's because as I often do with my class, when I first start to present this idea, mind you, I actually tried to be diplomatic with my students. And I when I introduced insulin resistance, I say what can we do? Change the diet to lower insulin. You can do that through a low-fat waves. Mind you, it's just you have to step away from any processed foods, and you can kind of get to that same point. But nevertheless, when I start to first introduce the low-carb aspect, that can be shocking to some. And that just kind of present the situation I asked them, "Can you think of essential amino acids? Are there amino acids that human must eat? Yep, and all 100 of my students are nodding along, "Yep, of course."

Geoff

Yep.

Benjamin B.

"Are there such thing as essential fatty acids?" You can already see where I'm going with this. And they're nodding along, 100 nods. And they can begin to see where I'm going with this when I say, "Are there essential carbohydrates?" No. And people want us to believe fibers are essential. No, it's not. Not at all. Again, that's a very polarizing type of sentiment, but my hope is, anyone listening to this, before they want to start throwing potatoes at me, this is a way of getting carbohydrates in my diet, mind you I eat carbohydrates anyway. I'm a dad of young kids, it's pretty hard not to. I'm not saying someone shouldn't eat carbohydrate. That's not what I'm saying. But I am saying I don't think it has any real role in human health, or human longevity. And I think we need look no further than the fact that it is not essential. You can truly eliminate that entirely from a human diet as we have seen done in people, as have been done, even in clinical studies with Vilhjalmur Stefansson, for example, and not only all of the rise of all these numerous anecdotes from these keto carnivores today, and other human cultures in existence still. We do not need carbohydrates, at least as far as I know. And I'm willing to be proved wrong. But the fact that there is nothing essential to a dietary carbohydrate, that to me settles it.

Geoff

But I think a natural extension is that now is that optimal?

Benjamin B.

I don't think so. But that's speculation simply because until we have a human study that can truly ... which is impossible, right? Track a ketogenic adherence throughout their whole life, and track the low-fat, semi-vegetarian people throughout their whole life, who's gonna live longer, we just don't have those kinds of death.

Geoff

And control that. Put them in the same kind of family structure, same environment, same everything.

Benjamin B.

Yeah, exactly. And someone wants to cite any of the kind of Seventh-Day Adventist's supported studies, looking at well, the vegetarians, are they living longer, versus omnivores? Not when we had studies that controlled for healthy user bias, they don't. And moreover, the evidence admittedly correlational that suggests in humans that after the age of like 60 or 65, that LDL cholesterol is protective, that the people with higher levels of LDL have better health, and better mortality, longer living when LDL goes up. I would suggest that, mind you that's not going to prove any point, but as someone's getting further and further away from the essential parts of the diet, which is protein and fat, we can all agree on that. Those are essential. Anyone has to even reluctantly admit that those are going to help LDL stay high, and helps the older person stay-

Geoff

Which would shock the standard cardiologists out there who are like, "You want to tell people that increase LDL who are under 65? You're crazy."

Benjamin B.

And I'm not necessarily telling someone to do that. But the fact is, the correlational evidence supports that. Numerous studies find that correlation. But could there be other factors involved? Absolutely. And it may not just be the LDL, but the correlation is pretty strong.

Geoff

I think that's almost its own episode talking about the LDL hypothesis, and how that relates to cardiovascular disease. And is inflammation, or instant resistance, is that more of a core driver. And I know that you mentioned Ivor Cummins, and some of the other folks have written a lot about that.

Benjamin B.

Yeah, Ivor and Dave, Dave Feldman. I wouldn't be the one to have that conversation. There are other guys who are much more steeped in that than me. And frankly, you know what? These guys aren't PhDs or MDs. These are what I call the PubMed warriors.

Geoff

They're software engineers, yeah.

Benjamin B.

The wonderful thing about that is just how egalitarian science has become, that it is so accessible. All the stuff that we're kind of kicking around, I think it is so important for someone to know that I did not step lightly into this realm of low-carb. It was a very deliberate and kind of uncomfortable journey for me. I was as much an advocate of the pure caloric theory, and saturated fat being the devil as anyone. In fact, maybe even more, because in my studies, when we were infusing palmitate into rodents, when we were treating muscle cells with palmitate that kind of prototypical saturated fat, man, we saw some massive insulin resistance start. And so I was as much an advocate of this traditional way of thinking as anyone.

Benjamin B.

And then it's simply, as I began to appreciate the relevance of insulin in disease more and more, and how insulin was driving insulin resistance, elevated insulin driving insulin resistance, and then driving disease, that started me looking into human clinical studies that we're separating patients based on diet. And that was when the whole thing started to kind of crumble. And I had to realize that my own opposition to saturated fat was because of the findings from artificial models where we were explicitly infusing, or directly treating saturated fat into these situations. And that is not the same as a human eating saturated fat. That is not analogous. That is not a fair comparison. So I had to not only realize that flaw in my own findings, but I also had to then be open minded to what was happening from the whole human physiological perspective, which shame on me, as a physiologist, I really hadn't been appreciating. So, my point in saying all of this is, I went through my own journey of saying, "Okay, I'm not believing any more dogma. Whatever I have considered as fact, I'm putting away, and I'm only gonna look at what has been published in human clinical studies and nothing else." And that's what took me to the conclusion I've come to, which is hormones matter, and controlling carbohydrates to improve the overall metabolic or endocrine Milieu elicits a greater metabolic improvement, than strictly trying to control calories. That was basically my conclusion in a sentence. And I'm okay if people disagree, especially if they have data, because they can show me a study well, and I can say, "You know what, that's a good study. Here are my studies." And then we can kind of say, "You know what, yep, maybe there isn't a consensus in the fact that you're tipping more on this side, I'm tipping more on this side, let's shake hands across this subtle divide."

But what I have no tolerance for, and this is especially relevant as a professor, when I have my students that will say, "Dr. Rick I wanna disagree with you." And I say, "Oh, isn't that just so cute, that you think your opinion matters, when I'm talking about fact. So you can't disagree with the study. You can try to find data to refute it, and until you do so, you darling little undergraduate," and as I pat you on the head, and mind you I love my students, but I just have no tolerance for that kind of sentiment. Don't bring opinion into this. You can't say I disagree with you. You can find a study that refutes the study that I've shown you. Because I know this is such a sensitive topic, I only ever show my students data. And again, I show the data on both sides of this. I really do. I try to be even handed. But to me the some tips in favor of carbohydrate restriction, at least in the context of improving insulin resistance as a vehicle for improving metabolic health. Mind you, people who are listening to this are probably already generally on that side of the fence, if you will. Well, let's not say fence, that's too divisive, on that side of the teeter-totter. But this is something people can find. And again, Ivor Cummins and Dave Feldman are such wonderful examples of this. And Tucker Goodrich, and other guy who was very active on social media, these are guys who don't have the credentials that people classically want to look at. And Geoff, I mean, you're a good example of this. These are people who've become deeply familiar with the research, not because their degree made them familiar, but because they just had such a drive and a curiosity to find that out. I submit that's a better way to do it, because when you have to learn something because of your degree, you have to, to get through your comprehensive exam, or your dissertation defense, you're going to learn it, but with that little bit of reluctance, that means you're going to forget it soon after perhaps. When you have learned it because it's a passion, and you just learn to navigate the resources, like Google Scholar, and PubMed, you can learn it all. And so, no one needs to ever just take me or you at our word. They should challenge this, and they should want to know for themselves because then whenever they find their conviction of how viable and real it is, it will be so much more.

Geoff

I think there's a kind sentiment. I think that is exactly the scientific method, is not about degrees or credentials. It's about talking about data. And if you have data that proves me wrong then, then we'll follow the data. That sounds like just coming from how you speak about it. It doesn't sound like you're dogmatic about any one specific point. But there's like a moving body of data that suggests something very different. Then there's no reason why I would focus on the ketogenic diet or ketones, if there's new data showing that that's going to kill me.

Benjamin B.

Yeah.

Geoff

I'm not trying to be suicidal, and I don't think you are either.

Benjamin B.

That's right.

Geoff

And then, how has this informed your day to day lifestyle? Are you constantly in Ketosis? Are you constantly low-carb? Has Your research informed your day-to-day life?

Benjamin B.

Absolutely. And you know what, when it doesn't, when a scientist hasn't been influenced by their own findings, if it does have physiological relevance to them, then they don't really believe what they found. To me, that really is just sort of a truism of life. That if you have this conviction, this kind of testimony, that what you know is real and true, it ought to have altered your behavior. And I use this example with my students. When I was a PhD student, a lot of my classes, and all of my research was that the medical school. And I would have to bike to the medical school and hospital on the other side of the road because that hospital medical school sidewalk was covered with all the nurses and doctors who were on their smoke break. They would have to leave hospital grounds to smoke. And do you know if that doctor was going to go back into a medical employment with a patient, and the patient had hypertension, and they see the patients smoking one pack a day, the first thing they'd say is, "Well, you need to really cut back on smoking." And yet the hypocrisy as the stench of their own cigarette is wafting into the room with them. No, that's a person who doesn't truly have this conviction, or maybe you could say, "Well, that's balanced with some addiction perhaps." For me, the evidence in my own findings with insulin and now with ketones more recently are so clear, and have such a relevance in human physiology, that I would not be doing myself justice if I weren't adhering to some of this. So to your question, I am always low-carb. That does not mean I'm always in Ketosis of course, and I appreciate that you separated those two things. I'm often in Ketosis as frequently as I may check, which isn't that often anymore. It was more often than I first was experimenting. But a part of this is just the practical aspect of me being a dad with young kids. Mind you, my whole family is fairly low-carb. Breakfast this morning, for example, was bacon and eggs, and nothing. But with my kids, mind you, they reluctantly ate the scrambled eggs, but they gobbled up the Bacon. So Bacon's like breakfast dessert for my kids. So, yeah, very rarely will there be a loaf of bread in my home, very rarely is their chips and crackers. And it's just more real food as much as my wife and I try to do that, which again, with little kids it's easier said than done. You know what I mean?

Geoff

Right.

Benjamin B.

And in a part of this is me also being practical as a father in that, if we're having family movie night, I'm going to eat popcorn with my kids. Actually, to be honest, not to let anyone indulge too much, I find that popcorn actually doesn't take me out of Ketosis. I can eat a lot that night, and movie night, for family movie night, and I'm well into ketosis the next morning. Nevertheless-

Geoff

Metabolically flexible.

Benjamin B.

Yeah, exactly. That is a perk of, mind you, controlling carbohydrates. But when my daughter made dinner for the family, and wanted to make grilled cheese sandwiches, I always use this example. I'm not going to pick the cheese off my daughter's sandwich. "So, daddy ..." "Yes, sweetheart. Daddy can't eat the bread, sweetheart. So I'm just going to get the cheese." No, that's crazy. I'm going to eat my daughter's grilled cheese sandwich, and I'm going to smack my lips, and give her a hug and kiss for making it. So I would say I'm a very practical low-carb guy, where when I can adhere to a low-carb diet, and it won't, especially in any way kind of affect my family dynamic, I'm going to do it. And then that means breakfast and lunch for me are always low-carb, always. There's never an excuse for me to not be low carb at breakfast and lunch. It's just so easy. Even if my kids have this very rare indulgence, sometimes make this buckwheat rice mix, and they can eat it with milk and cinnamon. I won't eat that. I either I'm fasting that breakfast, or I'm eating something else. But breakfast and lunch are always low-carb. And then dinner is often low-carb, but it kind of just depends on what the family's doing. I don't want it to adversely impact the family dynamic, where my whole family's eating something, and I'm just sitting there watching them eat.

Geoff

You mentioned fasting. I'm curious to get your thoughts on some of Satchin Panda's work with circadian rhythms and fasting. Do you incorporate that as well into your personal routine? So, to give you a sense of my general protocol, I'll cycle in and out of strict ketogenic diet, and then I'll usually have a pretty tight eating window, and I do run a 24, or 36-hour weekly fast. So I'll do a blend of fasting, low-carb diet, and then cycling in and out of a strict ketogenic diet.

Benjamin B.

Yeah, that's-

Geoff

That's kind of my ... dependent on if that kind of works well for my lifestyle.

Benjamin B.

I do the exact same thing, exact same ... As often, I'll do a 24-hour fast weekly. And that's typically on a Monday, frankly, where I find the weekend, just having that outside of my normal routine, and being around the family a little more. I do tend to indulge a little more. Although I hate to say it like that, the Monday ... because it almost is sort of reminiscent of the kind of eating disorder, where it's like this binge and purge. But I don't think that's what it is. Well, if it is, I at least I'm justifying it, which is maybe terrible.

Geoff

I've heard that comparison with some reporters. They think it's like an eating disorder. But I think Mike's snippy comment back is that, "Everyone being obese and over eating is eating disorder."

Benjamin B.

Oh, no kidding, no kidding.

Geoff

Right. So just, I think it's like we're just trying to be sensible here, in terms of just, if we're going to be repleting with plenty of glucose over the weekend, if we drink beers, or all of that, It is called sensible to deplete some of that glucose that's stored glycogen. I would just reopen the conversations. I would argue against that eating disorder kind of poke at this, because this is, I think a more sensible enlightened way of consuming.

Benjamin B.

Yeah, I agree. I guess I'm disclosing that is a possibility because I can see how it's low hanging fruit, where someone just says, "Oh, well you're doing ..." Well, just what I basically just said. So I can see how some ... mind you, I'd actually never heard anyone else say that. So in a way, it is kind of validating that someone else would have that perspective, even if they're using it as fuel against the low-carb diet. You're right though. It's obviously a lot better than what other people are doing, but I do it for the exact reason you just said. I have to a degree loaded my liver backup with glycogen. I just want to empty that back out, and to help my body get back into a lipid fat oxidation mode as quickly as possible. And I find I also just appreciate the simplicity of a fast, where I just tell myself I don't have to make decisions about food for the next 24 hours. It is in fact, I've heard a lot of people describe they actually do multi-day fast, which is something I've never really embraced. In fact, well, I haven't at all. But I can at least intellectually embrace other people doing it. I really appreciate the simplicity, where it just eliminates some of the decision making for the day, where it is I'm drinking water. And typically for me, when I am doing a 24-hour fast therapeutically, now I also do it for religious reason once a month, as a member of my church, but that's different, when it is for this metabolic benefit. I will drink water, and I'm often just spiking in a little hint of apple cider vinegar. And that's not as much for metabolic boost as ... although the although the apple cider vinegar may in fact do that. But I do it because I just like the flavor. It just helps me keep drinking water. I've really come to appreciate that little bit of tart. So typically on a Monday, it's not uncommon depending on the weekend. And just kind of depending on how I'm feeling, I may or may not do a fast through Monday. But even then, it really is just to seek this metabolic advantage of getting myself back into lower-level of liver glycogen, and all the perks that come with that, which is ketosis and lipid oxidation.

Geoff

Yeah. That makes a lot of sense. And I feel like I got to get you to experiment with a longer fast. The longest fast I'd ever done was a seven-day fast.

Benjamin B.

Oh, man, no. I kind of-

Geoff

Which is kind of a religious experience in and of itself. But I mean, I think we could go on for another hour if we have the time. So I wanna wrap up with one last question.

Benjamin B.

Geoff, but before ... One of the reasons I've been reluctant for multi-day fast is, I look at myself and think, right, I'm a middle aged man whose main physical priority, as oddly as this sounds with three little kids, I got a long game in mind. And my priority is I want to be a healthy grandpa. And so I'm thinking, what's going to help my health span? And that's going to be maintaining as much lean mass as I can. And so with that kind of as a priority, maintain lean mass. I have huge respect for Dr. Jason Fung. And he really does insist that there really isn't this loss of muscle mass. And again, I really respect what he's saying, but yet, the academic in me thinks, well that's impossible. How can there not be some muscle mass? And I bet if he ever listened to this, he'd be already thinking of numerous mechanisms. And people want to invoke growth hormone being up. But yet, I still think at the end of the day, if you were in genuine choleric restriction, how can the body not be expending some lean mass to fuel the body? I mean, it happens. And so, my reluctance in a multi-day fast, is simply because I just really shutter at the thought of losing lean mass, and I'm working so darn hard to keep it.

Geoff

No. I agree. And I think likewise, when I was doing some of these longer fast experiments, part of it is in terms of, yeah, I want to maintain my lean muscle tissue, obviously. And I think, I was about to just reference Jason Fung. And he sort of convinced me around the notion of, on these longer day fast, the nitrogen that you excrete out of your urine actually falls precipitously.

Benjamin B.

Right. You start conserving.

Geoff

So from that respect, you can serve your protein mass, and then you referenced the growth hormone spike. He actually has working with some athletes, that he's trying to time the growth hormone spike with heavier workouts.

Benjamin B.

It's clever.

Geoff

So his kind of story is that, to gain muscle or to maintain muscle you work out. And so when I was doing these longer fast, I was working out fasted. So I was like lifting heavy, which I actually maintain decent amount of strength doing lifts, but I just felt like I couldn't run. My aerobic friends felt really, really bad. And then this is not super scientific, but I was doing a DEXA scan, before and after a seven-day fast, and weekly, 36-hour fasts, for about a two month period. And, again, there's a lot of data, and a lot of time span there, but I actually saw increased lean muscle tissue, and reduce body fat composition. So I had a very similar concern as you, where I don't want to be melting lean tissue, it takes all this effort to lift all these weights, or do muscle ups. They build up some muscle, I don't want to just be burning that away.

Benjamin B.

And, frankly, Jason is a smart enough guy. And I mean that it doesn't surprise me that he would have some justification and evidence to support that. It doesn't surprise me. I guess even hearing it, a part of me just sort of revolts to the idea.

Geoff

I don't do it that often. I mean, that last time I did it was about almost two years ago now. I'm not necessarily trying to do this all the time. It's more of a just an equals one experiment, just to get a sense of how it kind of feels like. And then, of course, it was like sort of the longevity story, in terms of, kind of, vulture along those research around, can you recycle your immune system, and all of that stuff.

Benjamin B.

I think it's worth mentioning that when people invoke a lot of the benefits of calorie restriction, and Mr. Valter Longo, perhaps protein restriction more specifically, with all due respect as scientists, part of me, can't help but wonder, well, what happens when you continue to fuel the body with sufficient calories, and yet you've simply lowered insulin? That to me is the low hanging fruit that some people have addressed in rodent studies. And then human studies, people aren't quite as willing to acknowledge that, "Hey, you know what? Maybe it's not so much protein restriction. It's magic." It could just be that we're restricting insulin activation. And that, to me, one of the strong ... as we've already been kind of talking about, I don't do a ketogenic diet because I care as much about the ketones. Although over time, as I continue to do experiments with Ketones, I can appreciate them more and more as viable beneficial molecules for the body. But my main motivation is keeping insulin in control for every reason, including longevity. Because so many of the longevity studies are kind of skirting around this issue of, it's just simply lowering the insulin. And so to me, I've not seen a good evidence to refute that, that may in fact be the mechanism of longevity. It's not the protein restriction.

Geoff

I'm glad you brought that point up. I think a lot of the caloric restriction benefits. I agree with you. I think it's basically lowering of insulin story, and the caloric restrictions, kind of this mechanism of lowering insulin. But what if you could just do that directly without being caloric restrictive with a ketogenic diet or something, right?

Benjamin B.

Yeah. That's the magic.

Geoff

And apparently in the primate studies that showed that, they were comparing caloric restriction, and a healthy diet, versus a calorie restriction, and an artificial high sugar diet. And the one results showed that there was no change of life span, for with a calorie restricted healthy diet, versus a healthy diet for these primates, and the calorie restricted unhealthy diet versus had improved lifespan, versus un-calorie restricted unhealthy diet, which I think hearkens back to the point that you were talking about, that perhaps it's really the insulin as the driver here, not the calorie story.

Benjamin B.

I would say before we leave that topic, could there be a separate immune function or immune aspect of fasting? And I would say there could be, and I bet that is actually through altered gut bacteria. When you've done, basically, we know that the gut bacteria, the whole microbiome ... I say we know, and I think we know, I believe that basically kind of turns over every three days. And so, when you've gone beyond a three-day fast-

Geoff

That's interesting, totally. I've never heard of that before.

Benjamin B.

You basically starved all of your gut bacteria, and now you have given the growing appreciation of gut bacteria, and immune health, let alone gut bacteria in your logical health. There could be something to fasting and specifically immune changes that go beyond insulin control, and has to do more with what have we done to the gut bacteria in this prolonged fast, where if they aren't getting that roughage or something, and I don't just mean referred from fiber, because even carnivores have gut bacteria, but you have maybe changed the whole microbiome, maybe literally changed all of it, because they're starting from scratch, because you've killed off all the other stuff that had been in there, because they literally couldn't eat for however many days. So some of the immune benefit may be partly a function of this genuine shift in microbiome that is because of the fasting itself. But then any of the other longevity benefits, I think the big elephant in the room, the confounding variable is, well, what happened to insulin?

Geoff

That is a primary driver. If I had to put a percentage on it, I think it's probably through the dominant factor there.

Benjamin B.

Yeah.

Geoff

So I want to the wrap up with a final question. What areas of research are you most excited about? You're looking around ketones, looking out on insulin? What can we expect in 2019 coming out of your group? What do you think are the most promising areas of research?

Benjamin B.

The obvious one that I think will have the biggest impact, well, at least my own thinking is the one I mentioned earlier, which is the evidence that we're finding, and hopefully will get published this next year of ketones providing this boost in metabolic rate, via increased adipocytes mitochondrial uncoupling. So, basically, turning the white fat of subcutaneous tissue, making it more so called brown fat, and then they're more mitochondria and they're more uncoupled. However, perhaps some other kind of most exciting area is what we're finding with neuroplasticity, which is kind of biochemical corollary or surrogate I should say, of learning and the ability to learn and create new thoughts, learning new skills, retaining new information. What we do in this model, because we take the rat brain and make these slices, and I'm doing this as a collaboration with my colleague Jeff Edwards, who's the brain guy. It actually started with this idea of me saying, "Can we keep brain tissue viable when we eliminate all the glucose?" Because there's always this question that you can never answer in an in vivo situation, which is, does the brain actually need glucose, or is it just using it because it's there? We know that with long fasting, than even I would say a ketogenic diet-

Geoff

There's always some glucose.

Benjamin B.

We always have glucose, so the brain is always pulling in some. But it shifts to majority of beta-hydroxybutyrate as its fuel, and so there's this predominant shift to Ketones. But then the question still lingers, but does the brain need the glucose, or is it just using it because it's there? So that was part of the original thought here. Can we keep the brain tissue viable in the absence of glucose, maintaining all the osmotic gradients, and just using ketones as a fuel? And the short answer so far is yes, actually.

Geoff

That's cool.

Benjamin B.

But independent of that, we're measuring this neuroplasticity, which is one of Jeff's, kind of ... one of his bread and butter techniques. The classic kind of bath, when we put these brain slices in this solution to try to mimic an in vivo setting. It is a very high glucose setting. Which is very standard for almost any ex vivo or in vitro conditions. It's always high glucose. And so, what we're doing here now is just cutting down the glucose, and increasing the ketones to a situation that you would see in fasting, kind of this kind of 3:1 or 4:1 type ratio. And what we see is that the neuroplasticity is enhanced. We're seeing a significant improvement in these outcomes suggesting that the brain, at least with these assays, measuring neuroplasticity, is working better when it's fueled with ketones. And this certainly fits with the idea of people with cognitive decline, thriving when ketones are up. We've seen this in humans. There's very little debate on that. It's quite obvious evidence. This is providing a bit of a molecular mechanism. So it's pretty exciting. But because I'm not the brain guy, and Jeff is, that's my second most exciting. I liked the adipose mitochondrial story a little more. But they're both pretty provocative.

Geoff

Well, when they're out, I mean, that's going to shake up some of the scenes. I think those are pretty astonishing results. That's really cool.

Benjamin B.

Yeah, it's fun.

Geoff

I think there's a lot of interest with the neurological, can you improve cognition from a therapeutic side and also from an enhancement side? It was also very interesting to a lot of our listeners out here.

Benjamin B.

And, Jeff, you know what, I'll say that is the beauty of being a scientist. It is the glory of just getting paid to ask questions. I mean, think how cool that is, I get paid to just ask questions. So if I'm not teaching my class in any given day, I can just sit back in my office and ask myself a question for eight straight hours, and try to find an answer. Then come to the conclusion, okay, no one's answered this, let's answer it if we can. And mind you, there's not a lot of money in being curious, so scientists don't get paid too much. But it's a glorious thing. What we lack in salary will make up for just true intellectual freedom, to just get paid to ask questions. And these two questions, are the result of just me and some students shrugging our shoulders and saying, "Has anyone asked you this yet? No one has. Let's do it."

Geoff

This conversation is going to generate a lot of questions from our audience here.

Benjamin B.

Good.

Geoff

So, I mean, I definitely have to bring you back on the program to answer those questions. Thanks so much. This is actually a really fun discursive conversation. I mean, clearly a lot of shared interests here. And I appreciate your depth and nuance in exploring these topics with us today.

Benjamin B.

It was my pleasure. Geoff, thanks for the opportunity to talk. I really enjoyed it. And like you said, having this common intellectual ground, always makes for a very fun conversation, especially when it's grounded with some justified evidence.

Geoff

Alright. Thanks, professor.