He also worked for the company Insulin IQ and he is a scientist, he is a true scientist at heart, I think you'll appreciate that in this discussion. It does get fairly technical at times I have to admit because he does like to talk about the science and the specifics, but importantly we try and bring it back to how the science can apply to us as individuals in our everyday life. And you know when Prof. Bikman says something, you know it based on research, you know it's based on science.
And interestingly he came to the low-carb world through science whereas most people come to it through a personal experience, a personal connection and then start to learn about the science. He sort of came the other way and I think that makes him fairly unique but also fascinating.
So I love talking with Ben I love having scientific discussions with him and for you I hope you get a lot out of this from science but I hope you can take away some practical implications of what the science means and also a sense of Ben as a human being and how he lives his life by the tendance of keeping insulin low and how he helps to educate his family about that as well, but without crossing any lines, without being too overbearing with it.
And it plays it with the students as well and we'll talk a little bit about that. So a lot of topics, a lot of science but I think you'll enjoy this interview. If you want to get the whole transcripts please go to DietDoctor.com and maybe particularly useful for this one is we talk about some the science and some of the big terms and of course all the other wealth of information online at DietDoctor.com. Enjoy this interview with Prof. Ben Bikman. Prof. Ben Bikman thank you so much for joining me on the Diet Doctor podcast.
And that was right on the tail of work coming out of Harvard in the early '90s, finding that adipocytes, fat cells, secrete pro-inflammatory protein, cytokines. That to me was mind blowing. The idea that the adipose tissue is an endocrine organ.
That study, I think it was in '94, finding that adipose itself can secrete hormones, well, proteins which are hormones in some instances, that opened up a whole new area of interest for me. And that to me it's started my interest in insulin resistance. So anyway, I'm being too long-winded but learning that the adipose tissue could secrete pro-inflammatory cytokines and that in that obesity associated, or induced inflammation, then could cause insulin resistance, that started my interest in obesity and insulin resistance looking indeed in that paradigm, obesity causing insulin resistance.
And then so I did my PhD work with a wonderful scientist at East Carolina University. His name is Linus Dome. And we looked at how insulin sensitivity changed so rapidly in people post gastric bypass. So it was kind of this disconnection in metabolic status. They are still morbidly obese of course one week post bypass surgery and yet they had become very, very insulin sensitive quite quickly. I still think it's actually not more than just you basically starve the person for a week and look what happens.
But nevertheless I then followed that up with my postdoctoral work at Duke Singapore, that was more lipid induced insulin resistance. So my world was and still is insulin, insulin resistance and specifically making a research agenda that is focusing on the pathogenic side of insulin.
We talk about insulin like it's almost like a drug. You need insulin, here's your syringe. And yet there's a downside of course to hyperinsulinemia or when insulin is getting too high for too long. About five years ago... yeah... by this point... sort of started kind of moving into looking at ketones as independent signaling molecules. Just molecules in their own right, not metabolic garbage.
Bret: I want to get into all the specifics-
And looking at that point me... forcing myself to say... okay what is the best way to address insulin resistance? I'm a member of the American Diabetes Association of course, the rigmarole is, you know, whole grains, low-fat, high starch, pretty high starch and when I thought, I'm not going to rely on any textbook. I just want this to be a course that is based on primary literature... that's when things started to fall apart.
So I guess that's about eight years ago and it was maybe a year or so after that when I really appreciated the randomized clinical trials looking at low-carb vs. low-fat and I thought, boy this is all wrong.
I had always been healthy and I'd always elicited enough self-control just to stay lean and healthy, but once I really started losing my hair a while ago, unfortunately, I really thought to myself just from my ego's point of view, I can be bald or I can be fat... I can't be both. You know, I knew I had to convince a girl to marry me and I thought, "Jesus, if I can just at least control how lean and fit I am, then hair be damned."
But anyway, yeah, it was an uncomfortable growth, but it was not my personal experience in... you know, experiencing this incredible burst of health. I was already healthy, I was very active, eating generally pretty well even though on the wrong kind of direction, but still, like I said, manifesting enough self-control to avoid junk food which already put me in some pretty comfortable territory.
For me, my transformation was almost exclusively academic. It was- which again, as an academic it made that transition both more uncomfortable because I thought I knew what I knew, but also gave me much more conviction because once I'd seen what I consider the reality, I couldn't un-see it. I could appreciate those P values for what they were. That statistical significance carried a great impact when I really found it.
But there are others, and in fact it's frustrating for me to even remember, there are others across campus in different departments who have been very upset with my perspective and have made life a little difficult. But for me it has always been, "Here are the data. Show me where I'm wrong."
And here's a couple of other ones... please, prove me wrong. In all sincerity, please show me the study that number that the dietary guidelines are based on, that saturated fat should be no more than 10% of calories. Please, show me. Otherwise, leave me alone.
Ben: Oh, no doubt.
To me there are instances of what we call- I've heard it in a low-carb community and I don't want to get us off on a tangent so you pull us back if we need to. People will sometime say you adopt a low-carb diet and develop physiological insulin resistance and I actually don't agree with that.
There are instances in human physiology of physiological insulin resistance and that's the two Ps as I teach it - puberty and pregnancy. But sure enough hyperinsulinemia, at least relative to what the person should be. And that's always a qualifier. If someone is normally going to be a four units, micro units, and there are 10, 10 could be in fact pretty reasonable for someone else. But nevertheless to me insulin resistance goes hand-in-hand with hyperinsulinemia.
And what we see in the instance of a low-carb adapted, fat adapted individual who takes a glucose load and now their glucose tolerance appears to be worse. In fact I call that glucose intolerance. Which is not the same as insulin resistance. And we are splitting hairs, but I actually still think it's important, because at least to me, I don't know... I'm not comfortable citing or invoking the term insulin resistance if insulin is low because if we were to give that person a bolus of insulin, that's going to work.
Because protein somehow has become very controversial in the low-carb world, that protein can trigger gluconeogenesis the new production of glucose, so if we have too much protein we can get ourselves into trouble on a low-carb diet. It's sort of a simple way to think about it and the science of it is much more complicated and paints a different picture. So that's a long lead-up to give you a runway here to go with, because I am curious how you want to explain this.
Up until that point literally three years ago or so I had no involvement whatsoever. I was studying insulin and even ketones a little bit in my lab and totally oblivious to this whole world. I'd heard the sentiment... hearing people adopting low-carb diets and their obsession with... drinking oil, literally drinking oil.
People that were getting hundreds and hundreds if not over 1000 calories per day in oils added to their drinks and I thought that is not healthy. And hearing this fear of protein, that brought me back to a concept that I'd kicked around and thought about years prior - the insulin to glucagon ratio. You said it perfectly and George Cahill was the first researcher from decades ago who really looked at starvation and a lot of insulin.
He has a study called Physiology of Insulin in Man, this big beautiful review paper, it's so well done just to a quality of writing, etc. that you just don't really find. And I can say that there is a guy writing and trying to copy George Cahill... but he mentioned insulin as the fed hormone like you said, the hormone indicative of the fed state, but also the hormone that generally directs metabolism.
And what I mean by that is it directs the use of energy like you mentioned a moment ago is energy going to be stored or used or as I had introduced a couple of years ago or wasted and that's of course ketones. But nevertheless the insulin to glucagon ratio does give an overall reflection of is the body in a fed or a fasted state. The higher that ratio is getting the more it is indicative of a fed state. In other words store.
And inhibit so-called wasteful processes, like autophagy for example. And that's just a low hanging fruit when you talk about the opposite of the fed state which is fasted. Fasted state is a low insulin to glucagon ratio and the most obvious form or effective of fasted state is autophagy is enhanced.
And so when I was thinking about how to structure a conversation about protein I thought, let's look and see what happens in the insulin to glucagon ratio. And there was some delightful studies; it was kind of an amalgamation of studies but largely based on the work of Roger Unger from UT Southwestern. He's a glucagon guy, a legend in the glucagon research.
And his- I found an old study from him which looked at the insulin to glucagon ratio and how the low-carb insulin to glucagon ratio was almost identical to the fasted state and several points lower than the conventional Western diet. So it was pretty interesting to me this idea of what I like to call a nutritional fast, rather than a caloric fast.
So someone who's still eating and getting energy and yet their body is still behaving as if it's in a fasted state. There's mobilization of fat, there's activation of autophagy, even though they're not in fact hungry, not fasting. So anyway, finding ultimately the protein, somewhat could eat protein... and if someone was in a state of glucose excess, like getting the protein at the same time as glucose or underlying hyperglycemia, that exaggerated this insulin to glucagon ratio. In other words, insulin really spiked.
In contrast, if you're eating protein in a fasted state or a low-carb state, because those two in fact are quite similar, then there was essentially no effect from the protein. And so I was eager to share that message when I learned it. I was enthusiastic about it as well. But I have been delighted that insulin and glucagon, the kind of yang to the yin, have become kind of a part of the vernacular in the low-carb realm because glucagon is relevant.
I maintained the insulin is the hormone that has two hands firmly gripped on the steering wheel of directing energy but glucagon's got a hand there. But it is interesting to know the difference. Some people will eat protein and will in fact have massive glucose spiking effect. And it could be that if someone becomes a type 2 diabetic, their alpha cells, the glucagon producing alpha cells have become insulin resistant. That is in fact more work from Roger Unger, the glucagon scientist at UT Southwestern.
They found that part of what I like to say flips the switch from insulin resistance, which is hyperinsulinemia, but normal glycemia, flips the switch to go from hyperinsulinemia to hyperglycemia or over to type 2 diabetes, part of that is that the alpha cells become resistant to insulin's ability to inhibit glucagon production. So they become insulin resistant.
And that might be part of why the very insulin resistant type 2 diabetic or just in other words a certain amount of the population will in fact find that as they'd adopt more carnivore or more protein heavy version of the low-carb ketogenic diet, they might have some struggles with their glucose, they might have some struggles with insulin.
I know when we do what's called multiplex assays, we can measure or multi-analyte, we could measure insulin, leptin, cortisol, growth hormone all in one little batch of plasma from blood. Glucagon - uh-uh... it's an entirely separate test. It has its own set of chemicals that have to be added in order to isolate it and in order to quantify it. And again I don't know the reasons, but it's another beast.
Bret: I imagine- I actually haven't looked into this, I have to admit, so it's probably something that not many labs do. It's going to be a send-out lab, it's going to be expensive-
But again we're making some connections here, then perhaps we could take that one step further to say it's probably a person who is going to have an insulin to glucagon ratio that isn't favorable.
Now one last comment about glucagon, as people are getting introduced to that perhaps for the first time, there is a phenomenon I almost hate to bring this up called glucagon resistance and that could be instances of- when people have had liver damage like a hepatitis, like an actual infection. In those instances those are the very small group of people who- and I emphasize this, it is a small group of people who genuinely have this, but that's when someone who might start fasting and things get very bad for them.
So I have heard of- I learned of this one person who claimed they would try to fast and they were healthy. And many people are so addicted to eating that they can't fast without it being very uncomfortable. That is not what I'm talking about at all. But this person, healthy lean individual that fast... and things really got bad for them, profound headaches, extreme discomfort, they were able to find a physician who did a glucagon tolerance test. And this is documented in the literature where they inject a small dose of glucagon and then the expected effect is to see an increase in glucose.
Because glucagon will mobilize the glycogen from the liver. And this person didn't have it. So a failure to respond to the exogenous glucagon confirmed this glucagon resistance. And it exists, that is a real phenomenon, but albeit very rare.
Do we have to fast for five days to trigger autophagy? You know, is an 18 - 6 fast good for autophagy or is just low-carb good for autophagy? And how do we know? So give us a little rundown on autophagy.
And so it's a way of keeping the cell regenerating itself in a way, keeping its function optimal, maybe that's the best way to say it. And thus people have looked at autophagy as a key to longevity that if you can promote autophagy, then your cells are going to continue to work better, regenerating themselves in a way and I'm not saying that they're resurrecting themselves, but just keeping themselves functioning optimally and that would logically lead to greater longevity.
In humans of course we don't have any evidence to confirm that, but that's a lot of the rationale behind the caloric restriction studies. Caloric restriction promotes longevity and that's not a sentiment I'm endorsing at all but that's the general sentiment. Calorie restrict... that promotes longevity and the intermediate event would be it's because it's promoting autophagy. At least that would be part of it. The truth of it is insulin controls autophagy. If insulin goes up, autophagy stops, because autophagy is wasteful. Insulin wants to store.
Autophagy is getting energy, it's catabolic it's breaking down parts of the cell. Of course it's in the effort of keeping the cell optimal, but it is still breaking stuff down; it is catabolic. And insulin is anti-catabolic and it is anabolic. Those aren't the same thing necessarily. Insulin is anti-catabolic in certain instances like at the muscle it is anti-catabolic and yet it is anabolic in other places like the adipocyte.
So nevertheless insulin very much controls autophagy. There are other variables too, but insulin is the elephant in the room. So once again we can come back to that insulin to glucagon ratio and essentially ask what keeps the insulin to glucagon ratio in a fasted state. Because if you are fasted you are activating autophagy.
Now like I said earlier according to Roger Unger's work from decades ago- and in this is changed of course because we have higher sensitivity tests to determine insulin and glucagon now, but if I remember correctly the fasted insulin to glucagon ratio is around 1.5. If you eat a ketogenic diet your insulin to glucagon ratio is around 2.
If you eat a standard Western American diet it's about 4, so significantly higher. And so I can't say exactly where that cutoff is, but I would say if someone's keeping their insulin at essentially fasting levels, autophagy is running. Whether it's a caloric fast or what I call the nutritional fast, it's still going to be activating autophagy or won't be stopping it.
Ben: Yeah and one important caveat there and that sets back to protein. There are many people who promote longevity diets and the whole schtick of the diet is restrict protein-
That kind of challenges the whole longevity paradigm with protein being the villain. To me, if you want to control mTOR because you want to promote autophagy, well, then control insulin, and also acknowledge that we need to inhibit autophagy at some point we can't have autophagy constantly running in say our muscles and our bones. If so, they'd be always catabolic.
Protein and mTOR, but as you were saying, insulin is the much bigger player, which brings into this sort of cyclical nature of an occasional five-day fast where you're limiting protein but you're also limiting insulin because it's a fast. But you don't want to do that all the time. Obviously it's very difficult to do and reset your metabolic rate.
So, are you a fan of sort of intermittent fasting twice a year, three times a year, that kind of thing? Or do you think a steady state of keeping your insulin low is sufficient, you don't need to do more for longevity, for health?
And that's just something I'm very mindful of. I don't want to eat in a way that my two daughters especially, but that maybe sounds bigoted, but even my son would look at me and say, okay, daddy's not eating, so I'm not going to eat. And I am so worried about eating disorders, partly because I am a professor on a college campus and eating disorders are so rampant among especially young women at that age.
I'm terrified of somehow contributing to someone's eating disorder. But nevertheless, I enjoy eating. It's not something I enjoy going without. So, for me personally, I am a huge advocate of time restricted eating; 18:6 in particular. I will very rarely eat breakfast. I simply just don't enjoy it.
And I do my calisthenic body weight type workouts mid-morning and if I've eaten, I'm just more sluggish, I can't perform as well and I just don't need it, I don't need breakfast. So, these multi-day fast, I think they can absolutely have a place and I can deeply appreciate those in the low-carb community who are advocates of it. There's no question, there's an effect there. No question.
And I can look at that and nod my head and give them a thumbs up, but I'm not as much a fasting guy, I'm an insulin guy, and I'm thinking there may be other benefits of the fasting, like just breaking an addiction for food, realizing you don't have to have that when you think you do. But if I'm looking at fasting as a tool to lower and improve the insulin to glucagon ratio, which is in fact kind of how I look at things, I think there is a more comfortable way to do this, that is more sustainable.
So, that's pretty fascinating. And there's this whole world of are we promoting disordered eating by promoting a low-carb "restrictive diet". There are people on both sides of the spectrum. On the one hand, we're eating all the vegetables, all the meat, all the eggs, all the cheese. How is that restrictive? But on the other hand, in today's society it's seen as very restrictive.
Here's a clinical study, another one, another one, another one. No, she wasn't. And it was the way I was talking about it. And I thought, well how am I talking about it? I do tend to be a very boisterous, somewhat rambunctious speaker, especially when I'm trying to keep my students engaged for two hours... I have a two-hour lecture period.
But I hated the idea that it was only the professor who was talking about a low-carb diet that was triggering an eating disorder. And like you said a moment ago, when I show these students the data, what is the common theme of these studies is that it's calorie unrestricted. It's the antithesis of starvation. It's don't count your calories; eat as much as you can until you're full and then you're done. It's glorious.
It is not calorie counting. And to me, that is the crux of so many genuine eating disorders like anorexia or even bulimia. It is "I can't get that calorie into my system, I need to restrict the energy". So I rage against that idea and I really hope in fact the very students, or anyone who's claiming that's an advocate of a low-carb diet- mind you, when I'm in professor mode, I'm not advocating anything, I'm just showing the data.
And I kind of end up getting lumped in as an advocate simply because I'm the only professor who's showing it. And I do find I have to be a little more heavy-handed to make up for all the professors who aren't.
These are guys who've lost phenomenal amounts of weight and they just find they can't help but talk about it because they're so enthusiastic in a way and I'm not even, They have a conviction that I don't, because they felt it, I never really felt it, I just had the academic conversion.
And that's what got me looking into and scrutinizing low-carb diets as a legitimate intervention and what I now still consider to be the most effective way, calorie for calorie, to control insulin. Lower the carbohydrate, I mean it is so rational. So, my perspective... my paradigm had been how can insulin stay as low as possible?
And then I was seeing, as I started to look through the human clinical data studies that would refer to ketogenic diets. And I of course knew, I'd had nutritional biochemistry... I knew what ketones were, but because I'd had nutritional biochemistry as a student, I also didn't appreciate them because they are not talked about in any way except negative.
Bret: Right.
We're just about to publish a paper looking at gene expressions from different sections of the brain, human brains post mortem, looking at glycolysis genes in brains... of normal brains vs. brains with dementia versus ketolysis, the ability of the brain to use ketones. Whether the brain- dementia or not, ketolysis gene expression perfectly normal. Glycolysis gene expression, not at all.
And I'm talking about P values of 10 to the negative nine. I mean these are massively beyond any hint of coincidence. Dementia brains have a compromised ability to use glucose, and we know this in human studies looking at glucose tracking to the brain, radio imaging. And sure enough, if the brain can't use glucose, there's only one other fuel, that's the ketone.
But anyway, our fear of ketones means people don't want them at all. But back to my story I would see in these low-carb studies some calling it ketogenic, and I would kind of look at that with a little bit of a grimace and think oh, ketones are bad, so I don't want to study that or I don't want to look at that study.
But more and more realizing or appreciating insulin's firm control over biochemistry that ketogenesis is an indicator of controlled insulin, and that was my initial appreciation. I thought, alright, if someone's in ketosis, it simply means their insulin is low, and that's a good thing. So, even then, firstly I was looking at ketones as no more than an inverse indicator of what insulin was, because if insulin is low, ketones are elevated. That was it for a while.
And then I was starting to see more and more of these studies being published, looking at how ketones improve contractility of the heart, for example, greater ATP production, so the actual molecule that can allow the muscles to contract, more ATP production per oxygen consumed. Think about an ischemic hypoxic heart; there's less oxygen and it can maintain ATP production.
So, the ketones improving heart contractility, ketone reducing oxidative stress in neurons. And I was seeing this, and I thought, you know what, I want to step into that. And the greatest beauty of being a scientist is freedom - if I have a question, I can ask it. And if I see, do I have the tools to answer that question?
So we started asking some of these questions. And to this point, we've published the one paper looking at how ketones improve or reduce the oxidative stress from muscle cells and maintain increase, enhance muscle cell survivability. So they're more rigorous, if you will, more resistant to insults. And so, that was a paper that we published last year.
We were finally wrapping up our paper looking at the way ketones affect mitochondrial function in fat cells, you know, that's kind of like the browning of the fat-
Now, it might just be that I'm the man with the hammer and insulin is the nail and I see it everywhere, but even still, I maintain that lowering insulin is the main metabolic benefit. The ketones provide, you know- 80 % of the benefit of low-carb is from insulin control. The ketones provide the next 20 %.
Now, mind you, the more I'm learning about different molecules that you're eating from high starch foods there could be other factors, oxilates for example, and that's stuff I don't really know enough about. That might be a sprinkling in there, but to me, it is mostly controlling insulin.
I know a lot of our listeners have kids and probably wrestle with this. So, tell us some of the strategies and things you use with your kids to help them learn about health, to help them learn about nutrition and to be that role model for them.
That's not going to be my regret. Yeah, so for me... the low hanging fruit in my wanting to impress upon my children the importance of what they eat, it is that I talk about fat and protein as wonderful things. And I don't really give them opportunities in the house to get away from that. We don't have cereal, they never eat cereal for breakfast, ever.
We don't have bread, we don't have sandwiches for lunch, we don't have crackers. That's just not part of the snacking system. It is little pepperonis, it is cheese sticks, vegetable platter with some non-seed oil ranch dip, you now. We make a ranch dip out of ranch seasoning in whole fat Greek yogurt, or sour cream, my wife does that.
Anyway, I will tell them, depending on what kind of food they want, I'll say, how can we have a little fat here, a little more protein? I want my kids someday to go away to college and when they're living with their roommate and open the fridge they'll see skim milk and they'll say, "What's skim milk?" Or they'll see low-fat free yogurt.
You know, so that's the reality, it's far closer to the reality. It's not like my kids will just delightedly go grab a cheese stick. No, no, maybe one of them will and another one will complain about it and say, well, I want this.
And I'll say, we don't have that, we just don't eat that. And maybe someday it'll backfire, maybe someday they'll get out of the house, but they'll also know that they're healthy and they're fit kids, they know that. And they know that mom and dad are healthy and fit and some other moms and dads aren't.
I'll never forget when my son was maybe five at the time, he asked, "Is that person really sick?", because was talking about a very heavy, overweight person. I guess didn't experience all that much in his day-to-day life. He says, "Is this person really sick? Why is he so big?"
And then... it's a hard conversation to have with a five-year-old but I was sort of pleased that they understood that that's not right, and there's a reason behind that-
And they all want to show off their muscles, or wherever, but I'm a terrible example, of course, I'm a pretty teeny guy. But I just want them to focus on the positive. I don't want to scare them into eating - if you eat this way, you're going to look like that person. It's just rather, you've been blessed with a healthy, strong body, let's keep it that way.
This is what I want this healthy strong body, for me, daddy, mommy wants a healthy strong body, we are trying to do this by eating these kinds of things. So, they know it, as much as they might fuss about it. They will want ice cream. If I let them ice cream, they'd eat it all the time of course.
They're not those kinds of kids that are going to be offered ice cream and say no. No, no, they'd eat it. But I want them to know that's on one side of this food balance, and when we indulge in it, it is a treat and we enjoy it and then we know however that it can't be maintained and it can't be every day.
I'll wake up around 5:30, maybe five, and work on the book a bit and then the kids will start to wake up at 6:30. We're very strict with bedtime. The six-year-old goes to bed at 6:30, the eight-year-old goes to bed at 7:30, the 12-year-old goes to bed at 8:30.
I make breakfast, I'm in charge of breakfast, and we kind of rotate. It's bacon and eggs, it will be some egg muffins, some low-carb waffles made out of different kinds of whey and some different types of fats.
So if I'm going to plan lunch for the day I'll either bring lunch; some cheese sticks, some meat, some hard-boiled eggs, which are a staple for me, or I'll make a shake. And I love putting eggs in shakes, just rocky style kind of shakes. Actually a shake that I'm involved in making called Best Fats, I'll put that in there with some eggs and that's my kind of- that will be lunch and I'll keep it in the fridge.
And then dinner is dinner. Whatever the family's having- Mind you, my family being what it is, it's never usually high carb it might be moderate, but usually it's pretty low. Or there's an easy way to make it low-carb but I'm not going to be too disruptive to the family. If we're getting pizza, the kids are going to eat it, I'm fine with it.
I'll usually eat the toppings and the kids know it and they'll tease daddy about it. But that's an easy enough one to do that's not too disruptive. I'll usually do my work out around mid-morning, depending on the time of year and the semester I'll teach on Tuesday and Thursday afternoons, but most of the time is writing. And then a little bit of time in the lab now with my students; I have enough graduate students that they keep the lab running independently of me and then I'm working on a grant or a paper, usually one of those two things.
And it makes you incredibly trustworthy. We know when you're saying something it's based in science, it's based in academics, and if we find a way to apply it to our lives, then it should work and make sense.
I am mostly busy on Instagram and Twitter and my handle there is benbikmanphd, and not so much on Facebook, Facebook's a little too overwhelming. But I consult with a supplement company, Unicity, which is great, and then I also have my Insulin IQ group.
Ben: Thanks Bret.
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