Dr Rangan ChatterjeeFat Cell Scientist: 99% People Lose Weight & Stop Disease Faster With This Insulin Trick
EVERY SPOKEN WORD
110 min read · 21,939 words- 0:00 – 5:58
Insulin resistance defined: the two-part problem (cell resistance + high insulin)
- RCDr. Rangan Chatterjee
So Ben, you have been studying the hormone insulin and insulin resistance for many years now, and we now know that insulin resistance sits at the heart of so many different conditions: obesity, cardiovascular disease, strokes, Alzheimer's, infertility, PCOS, erectile dysfunction, skin health, longevity. So many different things, right? So I thought at the start I would ask you to explain what is insulin resistance, and why is it that one physiological state can have such wide-ranging effects in the body?
- BBDr Ben Bikman
Right. I am thrilled you're allowing me to start with answering that one question, because if we don't take a moment to define the villain of the story, then the rest of the story doesn't make as much sense. Insulin resistance is a two-part problem, and it's really important for people to appreciate the second of the two that I'll mention in order to understand the breadth of problems that stem, that grow from this diseased tree that we're calling insulin resistance. The first part of insulin resistance is what the name evokes, which is the idea that the hormone insulin isn't working as well as it used to, that some cells have become resistant to insulin's effects. Where insulin is coming and knocking on the door of the cell, some cells aren't responding as well as they used to. So that is what gives us the term insulin resistance in the first place. But the second part of this pathology, this two-part pathology, has to be articulated and appreciated in order to understand the diseases that come from insulin resistance. And that second part is that blood insulin levels are elevated. So that's a condition called hyperinsulinemia. These two things always come together in the body. Insulin isn't working perfectly at all the cells of the body, and blood insulin levels are elevated. And then the reason this problem can give birth to so many other issues, including the ones you mentioned and even more, is I believe it's simply a reflection of the importance of metabolism and metabolic health. There's so much of a description and a focus on metabolic health these days, and I applaud that. I rejoice in that. And yet I somewhat wince at the lack of clarity. Metabolic health is best defined as looking at the degree of insulin resistance, and insulin is the master metabolic hormone. It is the one hormone to rule all others. And, and if it's not working well, then metabolic processes in cells throughout the body are not going to work well. And then as metabolism is disrupted, health is disrupted. And then you have all those disorders you mentioned. Now all of a sudden the fat cells don't know what to do with the energy appropriately. Neurons of the brain are not getting adequately nourished because they can't obtain glucose. And then insulin has a lot of these unexpected effects, including affecting sex hormone production, thus giving rise to things like PCOS. So the relevance of insulin resistance, I think, is a reflection of the fact that metabolic health is a foundation to health in general, including chronic disease.
- RCDr. Rangan Chatterjee
Yeah, it's interesting. These terms insulin resistance and metabolic health, certainly in health circles, are getting used more and more. I, like you, have been talking about this for many, many years now. I'm not sure if you're aware, in-- back in twenty fifteen, and I filmed this in twenty fourteen, I filmed the very first documentary globally to show that a condition called type 2 diabetes could be put into remission in just thirty days. And, you know, it's crazy to think that was ten years ago now. And it was deemed r- by some people controversial at the time, although it's not deemed controversial today. But I think one of the problems is, is that those terms, I think the lay public doesn't know what it means. You know, they know what cancer means. They know what a heart attack is. But insulin resistance, metabolic health, you know-
- BBDr Ben Bikman
Yeah
- RCDr. Rangan Chatterjee
... those terms don't really land with them, I think, in the same way.
- BBDr Ben Bikman
Oh, I, I fully agree. In fact, uh, please pardon what may sound like a bit of a plug. When I first wrote my book about insulin resistance, I had toyed around with the idea of giving it a title of something like Insulin Resistance: Why It Matters and Why You Should Care, but I knew no one would care because to most people... In, in fact, to most people, insulin isn't even a hormone. Most people hear the word insulin and think of it as a drug, as a therapy for diabetes. And so it's been, uh, difficult to help people appreciate that insulin is the master metabolic hormone and that when it's not working well, diseases will follow.
- RCDr. Rangan Chatterjee
Yeah. Now, you are a big fan of the low-insulin lifestyle, as I am. Before we get into those sort of practical things that people can do to try and address this, are you able to give us an idea of the scale of the problem? I mean, I mentioned at the start all kinds of different conditions, basically to try and showcase to people that you're probably someone who wants to address this, unless you happen to be one of the very few people who are metabolically healthy. So it'd be quite, be quite good to get an understanding of how large is this problem, but then also what has actually caused it, because I suspect, you know, a lot of people out there have probably got some quite differing views on what the root cause of this problem is.
- 5:58 – 10:02
How big is the problem? Metabolic syndrome as a proxy for insulin resistance
- BBDr Ben Bikman
Hmm. Yeah.The s-- the scope of the problem is remarkable, and indeed, it's been a part of my motivation to continue to focus on this as a scientist for so many years. Uh, within the United States, I can, I can start there and, and then start to extrapolate a little bit because I think some of the data starts to get a little, uh, murky. Within the United States, the problem is sobering, where a report was published in two thousand and sixteen here, which did a, a national survey to try to understand the prevalence of the metabolic syndrome. And they found that eighty-eight percent of US adults had at least one part of this five-part constellation of, of problems that we call the metabolic syndrome, elevated waist circumference, uh, hyperglycemia, hypertension, and then I guess I could call the last two just dyslipidemia, uh, low HDL and elevated triglycerides. So that five-part problem is what constitutes the metabolic syndrome. Again, one, uh, at least one of those was found in eighty-eight percent of US adults. Quite sobering. Now, someone listening may be thinking, "Yeah, but Ben, you were asked about insulin resistance." What we call the metabolic syndrome used to be called the insulin resistance syndrome, and I-- it is a, a superior term because it's more precise. It, it doesn't quite have the ring to it like metabolic does, so it might not sound as good. But this suggests that eighty-eight percent of US adults have some problem arising from insulin resistance. That's quite sobering. Now, I know you have a very international audience, and some may say, "Well, it's just because the Americans are all so fat." Well, interestingly, and even somewhat paradoxically, while Americans are certainly quite fat and, and we're I think in the top ten, although not the fattest, but we're up there, we are not even in the top seventy countries when it comes to type 2 diabetes, one of the main manifestations of insulin resistance. Then if United States is barely in the top hundred in that regard, I think we're in the seventies, then clearly the rest of the world also has a problem. I don't think that mitigates the problem here in the United States metabolically, but it does suggest that this is a global problem. And when you, when you're able to look at type 2 diabetes, which is a more clearly defined clinical situation than insulin resistance, and, uh, we can revisit that later, insulin resistance just isn't measured, uh, or monitored appropriately. But if you just look at type 2 diabetes and use that as your surrogate of insulin resistance, then there are countries throughout, well, South Asia, South Asia, China, Southeast Asia, East Asia, um, the Middle East, uh, these are all countries that have far higher rates of type 2 diabetes than we do within the United States. So this is a global problem. As bad as it is here in the US, it is a-about as bad, if not worse, in many countries around the world, and even in ways you wouldn't expect. So, and, and that maybe brings me to the second part of what your question was, which is what causes it. I think to really appreciate the global scope and why is it that you can look at the United States, where we have such high rates of obesity and, and, you know, relatively normal or modest rates of type 2 diabetes, and then compare it to a country like Singapore, where I did my fellowship research many years ago, and one of my children was born there, and I love that place. Obesity rates are very modest, and yet type 2 diabetes rates are fantastically high, where Singapore is sometimes in the top ten of the most diabetic countries on the planet. There is something here that goes a little beyond diet now because these are very different diets in very different parts of the world. Although globally, the global diet is getting similar, and maybe I'll start with that point. For the sake of time,
- 10:02 – 17:49
Two origins of insulin resistance: “fast” (high insulin) vs “slow” (fat-cell hypertrophy)
- BBDr Ben Bikman
I, I, I will articulate two, two origins of insulin resistance. One is that I call-- One I call fast insulin resistance. This is where you can take humans and induce insulin resistance in hours, and as long as that stimulus persists, the insulin resistance will persist. And then once that stimulus goes away, the insulin resistance goes away. That one is chronically elevated insulin. So the more a person is eating a diet that is filled with refined sugars and starches, the more their glucose levels are spiking and the more the insulin levels are going to be elevated. And just to help people appreciate that, at a, at a now global level, the average individual wakes up, they've been fasting overnight, hopefully, their insulin has come down, and now the average individual spikes up their insulin with some sugary drink or some sugary bowl of cereal or some starchy, uh, baked item on a plate. And then they do something similar for their mid-morning snack, and then lunch, and then afternoon snack, and then supper, and then an evening snack. So the average individual is spending every waking moment in a state of elevated insulin, and too much insulin causes insulin resistance. This is something that's been shown to happen in as little as six days in very healthy college-aged students. You just give them-- start having them eat more refined sugars and starches. After six days, their fasted insulin levels are two and a half times higher, all while glucose at a fasted state stays normal, and that's one of the problems with just measuring glucose. But that is all to describe the fast insulin resistance. If you help insulin come down, then the body becomes much more insulin sensitive quite quickly. But that doesn't necessarily explain why in, say, the United States we seelower levels of insulin resistance than perhaps we see in Singapore. That's the slow insulin resistance where it's actually driven by the size of the fat cell. We have a mistaken view when it comes to body fat and insulin resistance or metabolic health in general. We tend to think that mass matters most. It doesn't. The size of the fat cell is what determines the metabolic consequences of that fat tissue. So if a person has more fat cells but they're smaller, they will actually be metabolically okay. Their blood markers will be fine, their cardiovascular markers will look all right. They're just quite chubby. This is what you tend to see in Caucasians and African ethnicities. They have this genetic ability to make more fat cells, and so if their body has a pressure to store more fat, which it is a whole other topic, then they will reproduce fat cells. And so they have more fat cells, but they're smaller, and small fat cells are insulin sensitive and anti-inflammatory, and both of those are important for maintaining overall cardiometabolic health. In contrast, on the other end of the spectrum, we have East Asians and South Asians and Hispanic, Hispanics here in the Western Hemisphere. Those are ethnicities that have a lower ability, a lower propensity to stimulate new fat cells. So as there is a pressure on that body to store more fat, the fat is left being stored in ever-growing fat cells. Uh, that's a process called hypertrophy. And so as the fat cells are undergoing ever more hypertrophy, they become very insulin resistant to try to stop their growth, almost like a, a naughty child who's filling a water balloon. The water balloon's about to burst if you put any more water in there. And so the fat cell senses it's reaching a point of maximum dimension, and it will become insulin resistant to stop its growth. Now, it won't shrink, but it'll stop. At the same time, the second point here is that as the fat cells are getting so big, they are pushing each other further and further away from capillaries and the life-giving blood that is flowing through them. And in an effort to try to correct that lack of blood flow and that lack of oxygen, the fat cells will begin secreting a host of pro-inflammatory hormones called cytokines, some of which will tell those capillaries to start growing off a new capillary line to feed those starving fat cells. But the overall process, the overall consequence of this will be very pro-inflammatory. So to wrap all of that up, the problem is very prevalent globally. We've already discussed a little bit why it's so relevant with leading to chronic disease. But we also, when we look at the fast insulin resistance, too much insulin causes insulin resistance, and that can be corrected by just bringing the insulin down by avoiding refined sugars and starches. On the other hand, that doesn't necessarily explain the ethnic differences that we see. Why is it that a moderately chubby South Asian now has all of the consequences of insulin resistance, like fatty liver disease, hypertension, and erectile dysfunction, whereas his Northern European Caucasian roommate, who's just as chubby as he is, is doing perfectly fine? That's not because of the fast insulin resistance, but rather because of the effect of the size of the fat cells, where he has fewer but fatter fat cells, whereas his colleague, roommate, friend has more fat cells, but they're smaller.
- RCDr. Rangan Chatterjee
Yeah, it, it's so interesting. I really appreciate the nuance there. If I can just try and summarize where we're at so far, we're talking about the fact that the world basically [chuckles] has poor metabolic health, and you mentioned a very alarming statistic in America, eighty-eight percent of people perhaps. I've seen some studies showing perhaps a little bit more, but a lot of people have problems with their metabolism, which very simply speaking, is the way we utilize and process energy in our bodies. And so of course, if you think about it on a macro level, this is a huge problem. You know? One, one of the sort of core things we need to do as a human being who wants to function in the world is to process and metabolize energy efficiently. If we cannot do that, yes, we're gonna have low energy and fatigue in the short term, but also this increased risk of many other kinds of conditions that we've already mentioned. Okay, so that's a starting point. But you then were sort of explaining very beautifully that America, whilst it has high rates of metabolic dysfunction and high rates of obesity and people carrying excess fat on their bodies, you're saying that proportionately, type 2 diabetes is not as high as you would imagine if the only thing driving the type 2 diabetes was metabolic dysfunction and obesity. You're saying that there's a subtlety, there are genetic predispositions based around our ethnicity, which means that we tend to store fat in different places. So me and you are a prime example here, right? So my parents came to the UK from India in the 1960s and 1970s, so I have a South Asian background, and therefore, from what you're saying, if I consume an excess of calories, I'm likely to store fat in a different way to how you are. Is that a reasonably accurate, uh, summary of where we are so far?
- 17:49 – 26:18
Why ethnicity and fat-cell size matter: personal fat threshold and inflammation
- BBDr Ben Bikman
Yeah. Yeah. In fact, and then, and then just to finish that thought or, or to tag onto that thought, my own ancestry primarily came from England, ironically. Where yours went to, mine came from, and so w- you and I do represent two very beautiful examples of the ends of the spectrum. So if you and I both gained-10, 10 pounds of pure fat, ge- genetics would suggest that I would simply just be that much chubbier and, and perhaps not as flattering in my Speedo. You would have that same physical consequence, but because your fat cells are now much bigger than mine, you are gonna have consequences of insulin resistance. And just to put a fine point on that, there was a study done that, that looked at fat, weight-matched men, Caucasian and South Asian, and they performed an adipose biopsy. We've done this in my own lab t- as well, where they removed a small portion of abdominal fat. And then-- And remember, these men looked the same, so if you s- had, had the two of us standing next to each other, let's just say we're about the same height, same overall body weight, they matched these individuals, and yet the fat cells from the South Asian men were on average, uh, with diameter over three times the diameter. And that's just the diameter. When you look at the volume, that is multiples, maybe ten times larger of a fat cell, even though the men were the same fatness and body size overall. They were con- they controlled for this. So yes, fat cell size will be substantially different for any given fat mass across, say, Caucasians and South Asians, just as an easy example, uh, on average. Now, one other point of nuance where, where you described what would have created that fat mass in the first place. Yes, calories matter, uh, definitely. That energy must be accounted for. However, there is a danger in invoking the principles of thermodynamics in humans because we are not steam engines. The origins of thermodynamics, which is fascinating, um, i- it has created an overly simplistic view, I think, that gets us into a bit of trouble because in this same study that looked at fat cell size, it-- between Caucasians and South Asians, the fasting insulin in the South Asians was about two to three times higher, actually mimicking somewhat the diameter of the fat cell. It was significantly higher, a multiple higher at a fasted state. And that is critical because as you mentioned, and I've mentioned now, I think, insulin is what helps the cells of the body know what to do with energy, and the fat cell is the perfect example. As much as calories matter, the fat cell must be told what to do with those calories, and insulin is the signal that tells the fat cell to grow. Now, again, I'm not saying calories don't matter, but when we look at what is driving that fat expansion, what is driving the body to store more fat, calories is one part of it, but we should also consider, well, what are those calories doing to the insulin, uh, level? And then what is the insulin then telling the fat cell to do? Because if you wipe out the insulin like it is impossible, utterly, totally impossible to hold on to, let alone gain any fat mass. So, so yes, calories matter, uh, but so too does insulin in telling the body, especially the fat cells, what to do with those calories.
- RCDr. Rangan Chatterjee
Yeah. Let's just stick on this example using you and me, 'cause I think it's, uh, given our respective ethnicities, it's-- I think it's a really interesting way to try and tackle this topic. So I appreciate the nuance around calories and of course, insulin is... You know, it's an anabolic hormone, isn't it? It tells the body to store things as opposed to break down things. And we are living in societies now where many of us, because of our lifestyle, and it's not just diet, but let's say because of the way we're eating food, amongst many other things, we're having these chronically elevated levels of insulin. So those chronically elevated levels of insulin are encouraging us all to store fat on our bodies. But the difference between you and me, uh, Ben, if we were the same height, and we were the same weight, and we had similar levels of high insulin-
- BBDr Ben Bikman
Mm-hmm
- RCDr. Rangan Chatterjee
... it seems as though your body is gonna take a very different approach to my body, right? So we both may have a high BMI.
- BBDr Ben Bikman
Mm-hmm.
- RCDr. Rangan Chatterjee
So we may both be regarded as obese by certain metrics, but you may actually be metabolically healthy with your high BMI, and so not have an increased risk of cancer, Alzheimer's, type 2 diabetes, heart attack, infertility, et cetera. You, you could basically be fat but metabolically well, and I could be the opposite. We-- I could have the same BMI as you, but because of my ethnicity, I'm not gonna make new fat cells. I'm just gonna use my existing fat cells and stuff them full of fat. They're gonna expand. They're gonna start leaking out inflammatory markers all around the body. Whereas you are gonna make new fat cells, and they're gonna all be small and tight, so you're gonna look fat perhaps, but-
- BBDr Ben Bikman
Mm-hmm
- RCDr. Rangan Chatterjee
... the markers for long-term health are gonna be sub- significantly different with you. Is that accurate, the way I've, I sort of articulated it?
- BBDr Ben Bikman
Yes, yes, perfectly. If I would just add one final comment, that this whole concept, when it was first posited in some, in, in maybe its clearest form, was described as the personal fat threshold.
- RCDr. Rangan Chatterjee
Hmm.
- BBDr Ben Bikman
So how much fat can a certain body hold before it starts to suffer consequences of that fat? And in broad terms, we would say Caucasians, I have the ability, my fat threshold is much higher. I can store much more fat before it has a negative consequence. And we would say your, in broad terms, personal fat threshold is lower. So you don't have as much-... storage capacity. So once you reach that threshold, you start to experience the consequences of it. And again, it's not fat mass, but as you've just reiterated now, it's the size of the fat cell that matters. And there are different genes that have variants. For example, just to really drill down, w- it's very, very likely that the average South Asian, for example, has a variant that is l- uh, uh, of a gene called PPAR gamma, and where P- and PPAR gamma is the main gene regulator that determines the birth of new fat cells. And this has been s- this has been shown to happen across ethnicities, where the PPAR gamma is a less active variant, whereas in, say, Caucasians, PPAR gamma's quite active. And, and people can actually see this at a, at a broad level. If anyone's ever curious to go and, and wants to have sort of a, a, a morbid evening of entertainment, you can look for TV shows about individuals who have gained just superhuman levels of obesity, you know, 500, 600 pounds, and they are almost always going to be Caucasian or African ethnicities. It's extraordinarily ... You would never find an East Asian. Uh, it would be extremely unlikely to find a South Asian, uh, pr- pretty much impossible. These are ethnicities that simply cannot get that fat because they don't have the ability to endlessly make new fat cells.
- RCDr. Rangan Chatterjee
Yeah, it's kind of interesting. If I reflect on my childhood and a lot of my parents' friends of a similar background, it, it would be quite common in the sort of Bengali Indian community for the guys as they get older to have thin arms, you know, thin legs, but there'd be a belly. And as they get older, you'd see that belly protruding out more and more, um, which is kind of interesting, which kind of plays in here to what you're saying.
- BBDr Ben Bikman
Mm-hmm.
- 26:18 – 28:51
Evolutionary lens: climate, sunlight, and why bodies may store fat differently
- RCDr. Rangan Chatterjee
But also, I always think about these things through an evolutionary lens. So I'm thinking, okay, well, what possibly explains this? Was there some survival advantage for Indian people like me, for example, many thousand years ago to be able to store fat in this way as opposed to Caucasians? I mean, what's your, your current take on that?
- BBDr Ben Bikman
Right. Right. Well, this, this theory can only go so far as, as so many theories when it comes to evolution can. Uh, but one theory would be this idea of where you're located on the planet, how much vitamin D you need to make, and the degree to wh- or how much sun you need to make vitamin D, and the degree to which that is a temperature that requires more insulation. So to, to put all that in more clear terms perhaps, let's say with my very fair skin, my ancestors could thrive in relatively lower light conditions, which would put them closer to the poles.
- RCDr. Rangan Chatterjee
Hmm.
- BBDr Ben Bikman
Let's say closer to the north, um, in this case. And so a little light a day, a little sunlight will penetrate my very fair skin very easily, make all the vitamin D I need, but it's also going to be quite cold. And so one adaptive response would be the ability to make fat cells, especially subcutaneous fat cells, the fat cells that act as a warm jacket going a- all around under the skin of my body, so acting therefore as a good insulator. But let's say your ancestors, with your darker skin complexion-
- RCDr. Rangan Chatterjee
Hmm
- BBDr Ben Bikman
... you need a little ... You're pr- you're not only protected from the sun, you're gonna get sunburned much less readily than I am, but you also need a little more direct light to make sufficient vitamin D.
- RCDr. Rangan Chatterjee
Hmm.
- BBDr Ben Bikman
That's als- that's going to put you closer to the equator, which is going to mean you don't need a lot of insulation. Fat isn't as protective. And you might not also have as much scarcity as my ancestors have, where I wanna have the ability to store a lot of fat in the event that-
- RCDr. Rangan Chatterjee
Hmm
- BBDr Ben Bikman
... winter comes in and I'm not able to eat for a month or, or, or more, and I have to just survive on water. Or, you know, or weeks, maybe a month is dramatic. But where, where your ancestors would've been closer to the equator, uh, you have much more direct sunlight, you're protected more from the sun. You don't need the insulation of, of body fat to keep you warm, but you also have plants that are growing food for you and animals grazing on other plants perhaps year-round.
- RCDr. Rangan Chatterjee
Yeah.
- BBDr Ben Bikman
And so you aren't as needed. You didn't have to adapt perhaps to as much scarcity.
- 28:51 – 30:16
Why glucose-only testing misses the early problem (and can worsen treatment)
- RCDr. Rangan Chatterjee
Yeah. It's fascinating, isn't it, when you think about these adaptations a- and how something that's problematic in this food environment might have been hugely helpful in a more ancestral one. One point I think we should make here, just to bring everyone along, is this idea that you're probably not getting your insulin checked by your doctor, okay? So listeners to this show, I hope by now are aware of insulin resistance, but the problem is, is that people will still go to their doctors and the focus tends to be on blood glucose. And I think we should just explain to people, Ben, if it's okay, that blood glucose can be quite a late marker. So there's many people going round, they're getting their glucose checked by their doctor at their annual medical, and they're thinking, "Yeah, everything's fine." But they don't realize that actually your insulin perhaps could be elevated for five, maybe 10 years, which no one's checking even before that glucose starts to go up.
- BBDr Ben Bikman
Yes. I think this is such an important point because it helps us understand the, why the problem has become-
- RCDr. Rangan Chatterjee
Hmm
- BBDr Ben Bikman
... so prevalent. It's because we simply aren't measuring the right things. You, you articulated this and laid out the question very, very well.
- 30:16 – 39:56
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- RCDr. Rangan Chatterjee
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- BBDr Ben Bikman
Our glucose-centric paradigm has caused us to miss the more relevant marker. And, and it's not a surprise. For a problem called insulin resistance, we should be measuring the insulin. But due to historical, and I would say scientific precedent and reasons, insulin was not measured. Scientifically, insulin was only able to be measured within the past fifty or so years. It's a much younger marker that has even to this day, even to this day requires a significantly more thorough examination in order to just measure. The testing of it itself is just more technically complicated. Glucose is now so easy to measure, and indeed, we've been able to measure it for over a century, that you can strap something on your arm that can tell you your glucose levels every moment of the day. We are years, decades perhaps, a, a, a good ten years out from being able to do the same with any hormone, insulin included. So there are just scientific technical hurdles that have prevented the early measuring of insulin. Now, that's less forgivable to continue to overlook because it is so much simpler now. But even still, it requires a formal blood draw, whereas glucose can be done with something as modestly as a finger prick or indeed slapping something on your arm for ten days. But even historically, through India, through China, uh, through Western Europe, the main manifestation of, of diabetes was glucose dependent, which was the excessive production of urine. In fact, diabetes means a lot of urine is being produced, essentially. And, and when there's too much blood sugar in the body, when glucose is too high, it overwhelms the kidneys, and then the glucose spills into the urine, which creates a lot of urine. So the main symptom of the problem was based on glucose. Why were flies attracted to that urine so much? It's because it was rich with glucose.
- RCDr. Rangan Chatterjee
Hmm.
- BBDr Ben Bikman
So, uh, we can forgive the historical focus on glucose, but again, I think it's becoming less forgivable as, as we learn more and the technology is catching up to enable much simpler measurements of insulin. So for insulin resistance, insulin must be the marker that we focus on. And you stated this well, which is the more we only look at glucose, we're waiting for the late marker because insulin resistance in its earliest form before it's type two diabetes is a state of elevated insulin but normal glucose. And so if glucose is the clinical marker that we're focusing on, it's going to remain clinically silent or undiagnosed. The GP or the physician may be identifying the patient's hypertension and thus giving them some prescription for a hypertensive medication. Or they may notice that their liver is getting fat and telling them to avoid alcohol and the person thinking, "I don't drink alcohol, so what's the problem here?" But little knowing that there's another marker, namely insulin, that if we measured it, we could have detected the problem much sooner, and then it could perhaps change the conversation much earlier in the life of the individual. Rather than waiting for all of these problems to continue to mount, we can recognize the problem in its earliest form by measuring insulin and then acknowledge that so many of these chronic diseases are a result of the elevated insulin. These are not diseases of elevated glucose. They're, they're, they're problems of elevated insulin and the insulin resistance that typifies that state. So the sooner we can convince... modern conventional clinicians to measure insulin, then the earlier we can detect the problem and, in fact, the better we treat it. Because that glucose-centric paradigm not only causes us to detect the problems too late, but for example, in the case of a person with type 2 diabetes, they've had el- elevated insulin, now we've waited until the glucose has risen. If we only have a glucose-centric view, then the clinician will feel justified in pushing the insulin up even higher in order to push the glucose down. Well, that is successful. It can lower the glucose. If you give a person with type 2 diabetes an insulin secretagogue drug or just insulin as a therapy, you push their insulin up even higher, and you will successfully lower the glucose, and yet tragically, we make them fatter, they gain weight very quickly, and they're up to three times more likely, for example, to die from heart disease, which is already the leading cause of death in people with type 2 diabetes. So our failure to have a paradigm that at least encompasses insulin not only leads us to detect the problems too late, but to treat them not only poorly, but even in a way that can result in greater harm to the patient. Our strategy should be measure insulin and do what we can to bring the insulin down. That will be, just by necessity, a strategy that's also bringing the glucose down.
- RCDr. Rangan Chatterjee
Yeah. I mean, I think one of the main reasons across the globe why we are unable to address this chronic disease epidemic is because the whole modern medical system is really set up around acute care, right? That, you know, it's very, very close to me. You look back three, four, five decades, our medical system is very, very good at acute problems like a chest infection, a heart attack, an accident. But we're using that same mentality to address chronic health problems, and that leads to big holes where we're not detecting people early enough. So a lot of people will know about type 2 diabetes, of course, and know what a problem it can be, but they don't realize that actually for five to 10 years before you got the diagnosis of type 2 diabetes, your insulin was up and creeping up. And had somebody told you that eight years ago, you might have gone, "Oh, Doc, what can I do about this? How can I address this?" We know Alzheimer's disease, by the time you get the diagnosis, it possibly started that process in your body 20, 30 years beforehand. We're now even seeing with autoimmune disease, there are certain markers that we can look at early which indicate, no, you're on the road to getting that autoimmune disease, but let's not wait until you're really sick. Let's kind of address it earlier. So I agree with you. I think fasting insulin is a phenomenal test. Unfortunately, here in the UK, it is still not widely available. I'm doing some work with a company to try and change that if I can, or at least contribute to that. But I know you've spoken before, Ben, that even if you can't get those blood tests, there are a couple of skin signs I believe that might indicate that we have an issue with chronically elevated insulin.
- 39:56 – 43:09
Spotting insulin resistance without labs: skin tags and acanthosis nigricans
- BBDr Ben Bikman
Right. Yeah, that, yeah, skin is a window to the metabolic soul. It gives us some insight where we can't maybe get that blood marker, which is gonna be more definitive. There are two specific problems that are surprisingly connected to insulin resistance, and conveniently, both of them occur in generally the same places and one's evidenced without having to remove one's clothes. So along the, the collar line of the neck is the most common site for both of these problems that I will articulate. S- and I bet as I describe this, people will begin to-- they'll nod their head thinking, "Oh, I've seen that before." So the first problem is one called acanthosis nigricans, which is the hyperinsulinemia, the elevated insulin is resulting in aberrant skin growth and aberrant melanin production. So both of those come together here, where the person will have around the ring of their neck a darker section of skin. So the skin's a little more pigmented and at the same time, it has the texture of crinkled tissue paper. So if we took some tissue paper, crinkled it up, and then spread it back out, it has this very just rough lined texture of the skin, and it'll go in a band around the neck. In that same location, a person may manifest with the second skin problem that reflects insulin resistance, which is skin tags. This is this aberrant growth of skin cells where it results in these little stalks of skin, like almost little mushrooms is, if it, uh, like, like a little mushroom. It's not a mound of skin like a big mole or something, but rather a distinct little protrusion of skin. So skin tags and then acanthosis nigricans are both extremely strong indicators of insulin resistance. Someone listening to this, if you see this on yourself, you can also get these problems elsewhere where the skin rubs, like at the armpits or the groin, so it doesn't just happen around the neck. But if someone has noticed these things, it is extremely likely that they have i- in fact, insulin resistance and maybe perhaps even somewhat advanced insulin resistance. But the good news underlying all of this is that, not to get too far ahead of the conversation, but it is reversible. As insulin resistance reverses, the skin gets back to its healthier state. So these are not permanent problems.
- RCDr. Rangan Chatterjee
Yeah. We'll maybe get to some of the biomarkers that we can check even if we can't get insulin a bit later. I'm really keen that we-At least address some of the practical things people can do. We've kinda set the scene that, you know, insulin resistance lies at the heart of so many different conditions, and we're not picking it up early enough. But let's assume that someone listening or watching this recognizes that, "Yeah, you know what? I'm pretty sure I've got a degree of insulin resistance," as much of the population does. In terms of practical things we can do, you know, where would you start to advise people on that?
- 43:09 – 50:22
Low-insulin lifestyle fundamentals: smart carbs + fasting windows + fat-cell shrinking
- BBDr Ben Bikman
Hmm. Right. Yeah, this is, in fact, the, the good news of all of this. As much as our conversation and any conversation of insulin resistance can be quite sobering and sound like a bit of a horror story, it at least is one with a happy ending because it is a problem that can be changed very quickly. You just had mentioned a moment ago how you, uh, explored the reversal of type 2 diabetes in as little as thirty days for what is, um, in, in many people's minds considered an irreversible problem. Well, these problems are only irreversible insofar as we may adopt solutions that only address symptoms. Because all of these metabolic problems, insulin resistance and everything that stems from it, they are problems of lifestyle. And so the food we eat, how we eat it, when we eat it, how frequently we eat it, is the culprit or the cure. And so that brings us to the cure version of it. Um, if, if the, the main driver of fast insulin resistance worldwide is too much insulin, then the solution is to give the body a break. And how can we bring insulin down? That is simply just by controlling carbohydrates. Now, I don't want someone to hear me say that and think I am declaring war on all carbohydrates. That is a, an extraordinarily diverse, broad macronutrient family. But the more carbohydrates are being consumed that come from bags and boxes with barcodes, the more the person is going to be living a life of hyperglycemia and hyperinsulinemia. And so we need to control carbs. So focus on whole fruits and vegetables rather than refined sugars and starches. That will result in much more modest glucose excursions and m- very modest, brief insulin spikes, and then the person will be able to enjoy times of lower insulin. And at the same time, we need to embrace a culture of just fasting. And I don't mean dramatic multi-day fasts, although people can certainly do that successfully. But even if the person just starts with mini fasts, we, we don't need to eat every hour or two. We don't need to be sipping on a sugary beverage every moment of the day. I would strongly encourage a person to eat a nice, hearty breakfast and let it be one in which carbohydrates are controlled and perhaps you're more-- y-you have fruits and vegetables, and you are liberal with proteins and fats, and then don't eat again for four hours. You don't need any snack. We're not, we're not little preschool children who get hungry in two hours. As adults-- In fact, as adults, we should be able to fast for twenty-four hours without much effort. I-i-in fact, if a person cannot fast for twenty-four hours, assuming that they don't have any underlying disease that would prevent them from doing so, that itself is a warning. An adult should be able to fast from calories, from food for twenty-four hours. But at a minimum, have these mini fasts that give you four hours or so between your three main meals of the day if you are gonna eat three meals. But the first one I think would be the most important, which is control carbs and then, and then be liberal with protein and fat because those have little to no effect on insulin and blood glucose levels. And then in a, in a longer, slower perspective and process, it would be the process of shrinking fat cells. And when someone is losing weight, that's what they should be thinking. They should be thinking, "I'm shrinking my fat cells," because that's actually what happens. You're not killing fat cells. You're not getting rid of fat cells. You're shrinking them. And, and as m-- But people have, of course, because of our calorie-centric view of obesity, they tend to have a calorie-centric view of weight loss. I, I think calories matter, but I would recommend that people start with a low insulin strategy because if you lower insulin-- Uh, my friend and collaborator, Dr. David Ludwig at Harvard University, he'd found that if you give people meals that have the exact same number of calories, but they vary in their ratio of carbohydrates to fats and thus have differential effects on what insulin will do, if you keep insulin low, metabolic rate can go up by almost four, uh, four hundred to five hundred calories a day just by lowering insulin. When insulin comes down, the body just starts to burn the metabolic engine a little faster. And then at the same time, when insulin's down, you start making ketones. And when you make ketones, you breathe those ketones out or you urinate those ketones out, and every ketone has a calorie load roughly similar to glucose. So now the person is just wasting, they're excreting up to hundreds of calories a day by just breathing and urinating out those calories in the form of those ketones. So the person can have a caloric shift of almost a thousand calories a day by just keeping their insulin down, depending on where they're starting. And, and so calories do matter, but I think when it comes to the fat cell shrinking journey, it's a more prudent approach to say, "Okay, I'm not just going to cut my calories. I'm going, I'm going to change my calories in an effort to lower my insulin. As I lower my insulin, I'm going to have a metabolic advantage of burning more energy and then wasting energywith, with ketones, and that's going to help me reconcile the calories. And this will result in a certain degree of fat cell shrinking or fat loss. And then if a person feels like they need to go further, that's where they could integrate some structured fasting in a more formal way. I have very strong thoughts on fasting, though, that is a little more nuanced, but in general, I have a favorable view. So to me, to sum that up, a person would benefit and improve their insulin sensitivity dramatically and quickly by simply lowering their insulin, by avoiding processed sugars and starches or controlling carbs. And then second, take that same approach to take your first step on a fat cell shrinking journey, and then calorie control will-- could be a second step if needed. But I think the best way to do that is through structured fasts rather than deliberately cutting calories or avoiding sources of calories like fats.
- RCDr. Rangan Chatterjee
Yeah. So many interesting points there, Ben. So firstly, you mentioned how a healthy, metabolically well adult should be able to fast for twenty-four hours. Now, the crazy thing is, Ben, is in twenty twenty-five, that is deemed to be a highly controversial statement by so many people, which to me is ludicrous if you just think about human evolution. If we were unable to spend twenty-four hours without having any food and we couldn't function and we got really sick, I'm not convinced many of us would have survived, right? [chuckles] So-
- BBDr Ben Bikman
Yeah
- 50:22 – 1:03:14
Fasting and women’s cycles: why timing matters (follicular vs luteal phase)
- RCDr. Rangan Chatterjee
... but yes, I agree many people struggle with that today. That doesn't mean that it isn't a good goal that's worth building up to at some point, right? If you fix your metabolic health, people will often find that they can fast for twenty-four hours, often quite effortlessly. Now, just on that point, do you think that applies to men and women, or do you think one of the sexes is more biased to being able to fast for twenty-four hours?
- BBDr Ben Bikman
Hmm, th-that's a great question, and it, it's a topic that's getting, uh, uh, more interest. I think there is some fascinating differences when it comes to metabolism between men and women. The two sexes are profoundly different, in, in some ways shockingly similar when it comes to metabolic function. But because women carry the metabolic burden of fertility, it's no surprise that their metabolism has a little more nuance. Progesterone, uh, carries quite a, a punch. It, it has quite a metabolic effect. And so during the luteal phase, when her progesterone levels go from essentially nothing to a lot, progesterone has a few different and, and meaningful effects that I think would make it harder for the woman to fast during that es- you know, that especially that week or so before the progesterone starts to come back down of the luteal phase, so the time after she ovulates. Um, progesterone has a central nervous system effect to promote hunger. It's never discussed as one of the hunger hormones. We talk about other hunger hormones, and we never include progesterone, and yet progesterone is significant. That doesn't mean a woman can't fast, but it will mean she's having a much harder time, um, doing so. And, and, and thus perhaps, uh, it would be a time to be a little more generous with yourself and, and kind to your body and not fight it quite so hard. But fasting would not be favorable to pregnancy if it happened too much, and, and moreover, especially not at the beginning of pregnancy, where she needs to grow not only her own body but also potentially the body of another little human. And so she wants-- the body wants to prime itself to be hungry. And so in the, in the event sh- that she was pregnant, progesterone is just starting to set the stage. It is, after all, the hormone of gestation. So the luteal phase would make it a little harder. Otherwise, I, I don't think there would be much concern, and indeed, I think during the follicular phase, a woman may find it easier actually because at any given moment, women are actually mobilizing and burning more fat than her male counterparts. In fact, this is one of the metabolic markers that I both love and appreciate. I appreciate what it shows us, and I appreciate the differences between the sexes, where free fatty acids are the marker of lipolysis or fat breakdown. And estradiol is such a promoter of lipolysis that at any given moment, a woman will have free fatty acid levels that are about forty percent higher than her male counterpart. This is absolute proof that her body is relying more on fat as a fuel. And women have more fat than men. In fact, back to our earlier topic, they're healthier with that fat because they have smaller but more abundant fat cells. So even in the sexes, within ethnicities, the, the size of fat cells explain the differences in cardiometabolic risk. Uh, a premenopausal woman is, is virtually immune to the consequences of having higher fat mass because she has just more but, but smaller fat cells. But to, to bring that all back to the topic of fasting, I think in that follicular phase, a woman may actually be able to fast more easily than a male because she's burning more fat than he is, and fat is the fuel of the fasted state. Ketones are as well, um, but that's a bit of a, a, a branch, uh, in topic here. But this all sort of touches on this concept of metabolic flexibility, where I, I-- which itself is once again derivative of insulin and insulin resistance. When the whole concept of metabolic flexibility and metabolic inflexibility was first identified and articulated at the University of PittsburghIt, it was quickly seen to be a consequence of insulin, where the metabolically flexible person will eat a typical meal and be in glucose burning or sugar burning mode. And then a few hours later, they h- they transition into the fasted state, and they go into fat burning mode. And even, even a relatively lean adult has hundreds of thousands of calories stored in their body as fat. So if you can transition to burning fat for fuel, you are now running on a, on a diesel engine that can take you very far-
- RCDr. Rangan Chatterjee
Mm
- BBDr Ben Bikman
... metabolically down the road. But some people are metabolically inflexible, as it was identified by, um, Goodpaster and Kelly, the two scientists who first articulated these points, where they eat a meal and they're in sugar burning mode, and then hours later, when they should be transitioning into the fasted state, they are not. They're still stuck in sugar burning mode. That becomes a problem because the human body does not have hundreds of thousands of calories. Indeed, the liver only has about two thousand calories stored as glucose that it can share with the body. And so if you have a hard time w-weaning yourself off of glucose as your primary fuel, as glucose starts to run out, the body senses a deficiency in fuel and then will promote hunger to try to correct that, even if there is abundant fuel stored in fat cells.
- RCDr. Rangan Chatterjee
Mm.
- BBDr Ben Bikman
If we're not tapping that fuel, then what good is it? Uh, we're not relying on it. That will drive hunger, and it will drive the person to have a very hard time fasting. And so I think when it comes to adults, and I just had a conversation with a lovely woman in my neighborhood saying, "Oh, I can never fast for twenty-four hours. I just start to feel so sick." I thought it's because you're stuck in sugar burning mode.
- RCDr. Rangan Chatterjee
Yeah.
- BBDr Ben Bikman
You've never allowed your body... And, and, and again, this is, insulin is, to maybe finish that thought because I hinted at it, insulin is the hormone that determines the fuel use. If insulin is elevated, the body is sugar burning. If insulin is low, the body is fat burning. And so even here, with metabolic flexibility and inflexibility and the ability to fast, we s-still cannot step too far away from insulin.
- RCDr. Rangan Chatterjee
Yeah. I mean, that's the irony, isn't it? When people are carrying excess weight that they're trying to lose, the irony is that there is a ton of calories on board in the fat, but they're just not able to access it, and they keep feeling hungry. And obviously, for many people, that's because they're stuck in the sugar burning mode. They can't access the fuel tank of fat. But if they could just unlock that, they would find that actually there is a ton of energy to sustain them, and I guess that's the point that they're all trying to get to. Now, there's a couple of things to tie together here, I think, Ben. So let's just back up to what you said about women. You used the term follicular phase and luteal phase. For people who are not familiar with that, could you just summarize that again, but put it in the context of, is that early in the cycle? Is that just before-
- BBDr Ben Bikman
Mm
- RCDr. Rangan Chatterjee
... their periods? And just sort of say when those phases are and, you know, in which phases are they more insulin resistant, and in which phases are they more able to fast? I think that would be really helpful for people.
- BBDr Ben Bikman
Yeah, yeah, yeah, thanks. Yeah, thanks for... Yeah, uh, let's, let's bring that down to more, um, kind of palatable language. Yeah, so right at, at the beginning of the early part of the cycle, when, when I describe the menstrual cycle when I teach it, I actually will rarely use the term menstrual cycle and rather split it up into its two component parts, what's happening in the ovary and then what's happening in the uterus. Now, the uterine cycle's not a part of this particular story. It's the ovarian cycle that matters most because it, it's the ovaries that are producing these hormones that are not only telling the uterus what to do, but, but also telling the body what to do with, with fuel and metabolism. So at the first part of the cycle, so leading up to ovulation, that is the follicular phase, where her ovaries will have follicles, eggs, if you will, that are developing and maturing. And then there will be this big surge of estradiol, the main estrogen, and then that helps one of the follicles, and there's some other hormones too, like luteinizing hormone, but I don't want to make it too complicated. But suffice it to say, during the luteal phase, we are deve- or sorry, the follicular phase, we're developing follicles and, and those are what's going to become... One of them will become the main follicle, and it will ovulate, and now she has the egg that has been captured and is moving down the fallopian tubes to be fertilized or to be eliminated. Um, now that was ovulation, when one of the follicles became dominant, and then it ruptured, releasing the egg, but then the follicle remains in a remnant called the corpus luteum, the yellow body. And the, the, that now determines the luteal phase, which is the, the, the follicle producing a lot of progesterone now. And again, it is an enormous swing. The male body has nothing comparable to this. Male fertility, certainly essential, but it is beautiful and simple like a barbershop quartet, whereas female fertility is like a two hundred piece symphony. There's so much nuance and controlling that has to happen here for it all to play out well. Now, back to the two phases. During the follicular phase, she is burning a lot of fat very readily, and even as estradiol levels are going up, estradiol is a hormone that promotes lipolysis. Now, it's a little more nuanced than that, but we can end it there and just say sh- it, she's gonna be much more insulin sensitive during that follicular phase, the first part of her cycle, and much more fat burning. Then after ovulation, during the follicular phase, she is going to, with elevated progesterone, uh, be a little hungrier and be more insulin resistant.Because progesterone actually is one of the few hormone signals that can drive insulin resistance, and this potentially opens up an entirely new topic, which is to simply say briefly, not all insulin resistance is pathological. What you and I have been talking about-
- RCDr. Rangan Chatterjee
Mm
- BBDr Ben Bikman
... is purely insulin resistance in the terms of pathology, illness, where insulin resistance is not serving a helpful purpose. It's only causing metabolic mayhem. But there are instances, and pregnancy is perhaps the most famous, where insulin resistance is physiological. It's happening for a purpose. It's meant to happen. That's why it's physiological. Progesterone is what's driving that largely, and the insulin resistance that occurs during gestation is occurring to help the body grow because if you can be pushing up insulin levels, you said it earlier, insulin is an anabolic hormone. It wants to build things.
- RCDr. Rangan Chatterjee
Mm.
- BBDr Ben Bikman
Well, she is going to be building a human for the next nine months. She's gonna be building her own network of new blood vessels and a placenta-
- RCDr. Rangan Chatterjee
Mm
- BBDr Ben Bikman
... and mammary tissue to feed that baby even once it's born because her work isn't over yet. And so it is, as I s- have said before, a metabolic marathon, and progesterone helps the process happen. So to bring it all back to answering the question more clearly, in the first half of the phase, the follicular phase, fasting would be easier, fat burning is higher, and her body's more insulin sensitive, which is what allows her to be mobilizing fat so much more easily. And then in the second half, during the follicular phase after ovulation, progesterone is going to make that all a little more complicated. She'll be hungrier because of progesterone's effects at the brain, and she will be more insulin resistant, making it a little harder to naturally transition between the metabolic states. In other words, metabolic flexibility will be a little more compromised during that time.
- RCDr. Rangan Chatterjee
Yeah, I love that. So that's, I, I hope, really helpful for people, particularly for women, uh, trying to understand why they may crave certain things. They may find things, uh, certain things easier in the first half of the cycle compared to the second half. And of course, that's a nuance that's much needed in science and health in general. This difference between men and women probably hasn't been spoken about enough, and slowly but surely, I think this is now starting to be addressed,
- 1:03:14 – 1:27:26
Tools and timing: CGMs, breath devices, circadian eating, and avoiding the evening ‘witching hour’
- RCDr. Rangan Chatterjee
probably not quick enough, um, you know, compared to what we would want ideally, but certainly at least now people are talking about the difference between men and women, and more and more research is going into that area. Bringing it back to some of these practical strategies you outlined before, Ben, you were talking very much about how we can eat in a way that keeps insulin low. Now, people are used to hearing about things like low-carb diets, low-fat diets, vegan diets, paleo diets. I would say that many people or a lot of people probably haven't heard of a low-insulin diet. And again, I think just to highlight the, the sort of key points so far, you are basically saying that from your research and from your reading of the research, chronically elevated insulin levels are causing all kinds of metabolic havoc in our bodies. And so it stands to reason that if we're trying to address that, and for many people that will be losing weight, that will be how it shows up in them, but not always, because I guess that's something we haven't addressed yet, that some people could be of normal weight, yet still have chronically elevated insulin levels that are causing them problems, which we can perhaps touch on. In essence, you're saying if we can have a low-insulin lifestyle, that's going to directly address the issue. Now, you mentioned breakfast, and I know in previous interviews I've heard you give, um, you're a big fan of changing your breakfast away from the modern sugary cereal, high insulin promoting breakfast to the more prioritize protein, have some healthy fats, and if you are gonna have carbs, have whole food carbs that ideally are grown above the ground and not below the ground, okay? That sounds, I think, to many people like a low-carb diet. Now-
- BBDr Ben Bikman
Mm
- RCDr. Rangan Chatterjee
... that term low carb, I think, again, can be confusing because low compared to what, right? [laughs] So some people regard 100 grams of carbs a day as a low-carb diet. Some people regard under 25 grams of carbs a day as a low-carb diet. So broadly speaking, would you say that your approach is in favor of a low-carb diet?
- BBDr Ben Bikman
Hmm. Y- yes, it, it, it is, but I would say I, I, I didn't use the words low carb on purpose.
- RCDr. Rangan Chatterjee
Yeah.
- BBDr Ben Bikman
Where when I say control carbs, maybe another way of describing this would be a smart carb approach.
- RCDr. Rangan Chatterjee
Mm-hmm.
- BBDr Ben Bikman
Because after all, what if you... E- e- for me, that's not so difficult to do. My, my culture, my food culture, my family dynamic, the, the environment I'm in, it's relatively easy for me to adhere to a low-carb diet, and that's certainly how I describe my own diet. As a, as a middle-aged dad with kids at home and a very busy family life, I am generally low carb, but that's not to say my whole family is, but I f- just find prudent ways to do it. A- and, and I'll, I'll come back to breakfast in just a moment because I think that's... There's some important timing to all of this. But when I have conversations with my friends in India, that's... A low-carb diet, forget about it. That's, that is a, maybe a, a culture that has more carbs in its diet than maybe any other because of just some avoidance of meat, uh, and which, which I am incredibly understanding for. That's why I mention these kind of cultural differences that we start to see. And yet I know many, many Indians whoa-adopt a smart carb diet. And, and I think it does just come back to scrutinizing the quality of the carbohydrate. And you said it very well, is the carbohydrate growing above the ground? And then even when it comes to fruits, some fruits have very modest glycemic impacts, whereas some fruits have substantial glycemic impacts. And so there are ways to be smart about your carbohydrates that don't necessarily require you to be eating very low carb, l- very or, or any degree of low carb. You could still have a primarily carbohydrate-based or plant-based diet, but you're just being smart about those plants. And what they would all have in common, whether a person is coming at this approach to reverse insulin resistance from a, a, a meat-based approach, an omnivorous approach, or even vegetarian or even, even dare I say vegan, what they will all have in common is an avoidance of carbohydrates that are coming from bags and boxes with barcodes. So they will all be avoiding pro- ultra-processed foods. And, and I s- as I see the global trend, certainly within the United States, moving towards scrutinizing ultra-processed foods more, I rejoice. I think that is a tremendous win where we're now getting healthier fats, and we're getting carbohydrates the way perhaps they were intended to be consumed-
- RCDr. Rangan Chatterjee
Yeah
- BBDr Ben Bikman
... which is in their whole food form. And then to bring it back to breakfast, I, I'm an advocate of controlling breakfast simply because, at least in my own experience and what I see anecdotally, it's the easiest meal to control because it has the least impact on a person's overall life. And, and maybe I'm looking at that from the perspective of a family man, where, where there's some interesting evidence when it comes to intermittent fasting, where it's very clear that if a person eats earlier in the day, the metabolic outcomes are superior. So studies show that if you eat breakfast and lunch and you fast through your supper, you are-- you have superior metabolic outcomes than the group that is fasting through breakfast and eating lunch and supper. However, even though I can acknowledge those data as a scientist, that will not work for me because I am a husband and a father, and I'm not going to not eat dinner with my family. That is what I hope, in an ideal society, the most social of all the meals, ideally. The family has gathered together around the table, and we're all eating dinner. And so for me, it's not an option to fast through dinner. My wife wouldn't allow it, and it would be weird anyway. Uh, and, and so I wanna have dinner with my family. So I choose to fast through breakfast because it is, uh, easier on me socially. My family dynamic allows it. Even though I know the data suggest it's not superior, it's the best I can do in my situation. So I fast through breakfast. I have a big lunch, and then that help-- By having a nice hearty lunch, it will help me control my supper consumption more easily, and then it will also make my evening snacking easier because-- to avoid it, rather, to be clear, because that is the witching hour when it comes to food and habits and addictions. The average person can be walking by a plate of cookies all day and not be tempted to eat a single one until around six PM. Six to nine PM, then all of a sudden, this little gremlin comes to life inside their brain that makes it a, a Herculean effort to, to deny themselves that indulgence. Even me, as much as I know, a-a-as, as informed as I am, my knowledge set when it comes to metabolism is expansive. And yet it just goes to show the difference between knowledge and, and application, that knowing something, and I would want to state this quite emphatically, uh, to anyone listening and with empathy, I wouldn't-- I would hate for someone to hear our conversation and think, "Boy, these points are so simple that they're making. Why do I struggle?" Because knowledge is not the same as implementing.
- RCDr. Rangan Chatterjee
Mm.
- BBDr Ben Bikman
When you start to talk about habits and diet, especially carbohydrates, that is an honest to goodness addiction, potentially, where in all of the neurobiology of addiction to foods, there's no evidence of addiction to fats and proteins, and not fats alone. It is-- The common variable is always carbohydrate. Now, again, I'm not waging war on carbs to say this, but that is the one thing that can be manipulated in such a way, adjusted, and tweaked to make us crave it. It is something salty and crunchy or sweet and gooey that we start to crave, and it's going to-- what they will all have in common is a base of a refined starch or sugar. So I say all of this with empathy, but I have found that if I have a hearty lunch so that I go into my supper and evening still a little full from lunch, it is much easier for me to control those addictions or at least bad habits in the evening-
- RCDr. Rangan Chatterjee
Yeah
- BBDr Ben Bikman
... that are so abundant.
- RCDr. Rangan Chatterjee
Ben, I think one of the things people really love about you is, yes, your passion, yes, the intricate and extensive knowledge you have around this topic, but also the fact that you are willing to acknowledge your humanity and the fact that despite you knowing the perfect way to construct a lifestyle, you also have real world modern family life limitations. And I think there was a really interesting point in what you said, which is-- which we could perhaps expand on, which is this idea that there are multiple levers that one can turn to give them a low insulin lifestyle. And you're not gonna be able to do all of them, probably. So you have to choose the ones that align with the other parts of your life.And what you said about evening family meals, I think is a prime example where for many people, if you just stopped at saying if you eat earlier, that's better for your metabolic health. And I've seen all those studies, and it's pretty clear to me that for most people, if you front load your calories, uh, in the day, I think there's some good Spanish studies, if you eat most of your calories before 3:00 PM, you have better metabolic outcomes even if you consume the same number of calories. You know, that is pretty remarkable when you see that. So circadian biology plays a huge role as to how we metabolize things and when. I also, like you, have young kids, and I want to have an evening meal with them as much as possible. So there are other ways to pull those levers on a low insulin. So you miss breakfast, you know, and you find that this big hearty lunch means that you're still a bit full in the evening, so you're not gonna overconsume your meal. You've also acknowledged, you know, the witching hour, and I know in previous conversations you've been very open about, you know, the problem you have avoiding sugary cereal to the point where-
- BBDr Ben Bikman
Yes
- RCDr. Rangan Chatterjee
... I believe it's no longer in the house, right? Is that right? It's still the same? You don't keep it-
- BBDr Ben Bikman
Yeah
- RCDr. Rangan Chatterjee
... in the house?
- BBDr Ben Bikman
Yeah. No, it's, it's, it's because it starts to call out to me. And that, that, that, that siren call, it's like a sailor jumping overboard to drown himself. In my case, it's drowning in cereal.
- RCDr. Rangan Chatterjee
Yeah. BON CHARGE are a wellness brand that have a fantastic range of products designed to help you feel better, live better, and sleep better. From blue light glasses to red light therapy devices and beyond, BON CHARGE make it really easy for you to prioritize your wellness at home. And I myself have been using many of their products for well over five years now. One of my current favorites is their Demi Red Light Therapy device. I've been following the research on red light therapy for many years, and the potential benefits include enhanced recovery, better skin, improved eye health, and also improved sleep. Now, since I got this panel, I've been sitting in front of it for about 10 minutes every morning whilst reading and 10 minutes every evening, and I'm definitely finding that I feel more relaxed. I'm falling asleep much faster. And overall, I would say I've had a big increase in energy. To get 20% off all of their products, go to boncharge.com/livemore. I've been drinking KETONE IQ for about 12 months now when I need to focus and get dialed in before a podcast recording or a writing session, and also before I work out or go for a run. And honestly, I've been really impressed, not only how it makes me feel and perform, but also with its taste. Whether you're trying to focus on an important project, stay clear-headed throughout the day, or juggle multiple things on your to-do list, KETONE IQ delivers clean brain fuel that helps you think sharper, longer, and smoother. It's backed by science and trusted by athletes and high performers all over the world. So if you're looking to push yourself harder, recover faster, and feel sharper under pressure, then why not give KETONE IQ a try? Visit ketone.com/livemore for 30% off your subscription and get a free gift with your second shipment. Click the link in the description box below or scan the QR code on screen. So I guess there are many ways we can try and lower insulin, right? You, you mentioned if you already prioritize protein, increase healthy fats. Those things by and large don't tend to drive up insulin. Um, you know, be careful with your carbohydrate intake. But also the timing of food I think was really interesting. So I have spoken before how I believe a CGM, a continuous glucose monitor, is arguably one of the best behavioral change tools I've seen since I started practicing. Um, I've seen very few things help an individual understand the impact that food has on their body like a CGM. Uh, perhaps we can talk about the pros and cons of a CGM. At the same time, I just wanna add something else that I've been experimenting with over the past few months, which is a Lumen device. I don't know if you've seen them or not. It's a-
- BBDr Ben Bikman
Mm-hmm
- RCDr. Rangan Chatterjee
... breathalyzer. They measure the composition of, um, you know, oxygen and carbon dioxide as you're breathing out and make a calculation on how much you're fat burning versus how much you are carb burning. And again, why I find devices like this so interesting, these N equals one experiments that we do on ourself, I, like you, I'm very familiar with a lot of the research on metabolic health. And I would say for many years, I eat pretty well, okay? But getting that Lumen device, and when I in the morning I would check waking up, am I in fat burning or sugar burning? I could see a direct correlation for me between, A, how many carbs I had at dinner, as opposed to whether I'd flipped into fat burning in the morning or stayed in carb burning, and the timing of my evening meal.
- BBDr Ben Bikman
Mm.
- RCDr. Rangan Chatterjee
So simply using that device helped reinforce in my head, "Hey, Rangan, be mindful in the evening with respect to how many carbs you're having." Even whole food carbs I found it was happening with. And also it helped me shift my evening meal just about an hour earlier. Now, I was able to do that in the context of my life, but that was very powerful because just by doing that... And I actually think the earlier dinner was more important than the carb intake. When, when I actually compared the two, I would find that if I had my evening meal at, let's say 5:00 PM-You know what? In the morning, when waking or an hour after waking, I was-- whenever I checked it, I was fat burning, which is of course what you want to happen overnight. It's something you wanna flip into fat burning. So I mentioned a couple of things there. I mentioned the CGM, I mentioned the Lumen. Do you have any comments on, on what I just mentioned?
- BBDr Ben Bikman
I do. I am, like you, an enormous advocate of these technologies because I think it helps a person-- I think the reason it works so well is that it helps a person become their own motivator, where they don't have to have you or I wagging a finger at them and telling them what to do. When they see... I have known perhaps no single thing that has resulted in more behavior change than, uh, you might have just said this exactly how I'm saying it, than a CGM. When a person sees, when they get to pull back the curtain and witness the metabolic consequences of what they eat or drink, they, they change. They don't like what they see, and they, they, they don't-- they feel it as well, where they now can see something. There's a visual representation of what they're already feeling, which is the, the consequences of this massive hyperglycemic variability that may linger for up to four hours after these sugary, starchy indulgences. And then they see how better they feel when the line is, has a lot-- is a lot quieter and lower because they're controlling their carbs and just being smarter with what they're consuming with starches and sugars. I'm a big advocate of the CGM. I, I think the Lumen device is very clever, and I, in fact, am thrilled. I know they just created a version that can measure ketones at the same time.
- RCDr. Rangan Chatterjee
Hmm.
- BBDr Ben Bikman
And, and ketones are, as much as we have a, a, a perhaps a, a generally negative view, th-in their simplest way, they are simply evidence of fat burning. If you are burning fat, you are making ketones. That is just the way it goes. It, it is simply fat. Ketones are simply consequences of the liver burning a lot of fat, and that happens as insulin comes down. So when, with the, with the addition of the ketone monitoring as well, I think the Lumen is really putting itself in a strong position to monitor metabolic health. And, and I know the-- I've had conversations with that group, and I love them a-as people. They just are-- seem like really delightful people.
- RCDr. Rangan Chatterjee
Can I just, just touch on a, a key point there? We'll come to ketones 'cause I'm fascinated, um, by that topic. Around CGMs, for people who don't know, uh, CGM stands for continuous glucose monitor, and it is, you know, a real-time, uh, approximation of what your blood sugar is doing, okay? Your blood glucose is doing. Which allows you to see, oh, when I eat this food, you can see what happens to that glucose, how high it goes, how long it stays elevated for. And of course, we want, by and large, our food to not spike our glucose really high, and even if it does go up, we want it to come down relatively quickly. We've also, early on in the conversation though, kind of mentioned how medicine is a bit hyper-focused on glucose, and that's a late marker. So in case anyone's getting confused by what we said earlier, and now that we're sort of saying y-you know, a CGM can be really useful, um, can you just help people understand that? Because on one hand, we're saying glucose is late, we wanna be focused on insulin. At the same time, we're then saying that a CGM is really helpful because it's telling us about our blood glucose.
- BBDr Ben Bikman
Mm. Right. Right. Yeah, I can see, um, how that might be seem a little incongruous. The value of the CGM is that it allows us to measure it-- glucose in its dynamic states. The problem with the person going into their GP or clinician every year for the fasted blood test is that fasting glucose isn't going to tell you the story.
- 1:27:26 – 1:51:39
Ketones and exogenous ketones: brain fuel, performance, and the ‘high insulin + high ketones’ paradox
- RCDr. Rangan Chatterjee
Yeah. It's so interesting. Okay, so let's go back to what you were talking about with respect to ketones. Okay, so first of all, I'm super excited to hear that Lumen are gonna start measuring ketones soon. Uh, that's very exciting. You also mentioned that, you know, people may have a negative view of ketones. They, they may have heard it in the context of a ketogenic diet, but you're essentially saying, wait a minute. Generally speaking, if you're burning fat, which many of us are wanting to do, um, and would benefit from doing, our ketones are going to go up. Is that always the case if you're burning fat, the ketones are gonna go up?
- BBDr Ben Bikman
100% of the time. Yes. Yes, so ketones are proof positive of fat burning. Now, it, it takes a little time to get there. So the average adult, in, in, in just-- I'm gonna mention children in just a moment to help people understand just how evolutionarily relevant ketones are to humans, uniquely to humans, interestingly. And there's interesting ideas on evolution that explain this. But with, with about 16 hours or so of fasting, a pers- an adult should start to have detectable levels of ketones in their blood or in their, in their breath or in their urine. And all of those are places where you can measure ketones, and a person could get devices or measuring devices to detect it in, uh, every one of those instances. So around 16 to 20 hours, ketones are coming online, if you will. Now, interestingly, if you look at fasting in a newborn human, a, a, a newborn baby will, or just a baby in general, an infant, will, with- within just about one or two hours of fasting, will have ketone levels that get higher than an adult will in one full day of fasting. So the newborn baby gets into a deep state of ketosis extremely quickly, extremely quickly. And, and it is in fact so essential to brain development that if, that if a baby is born premature, the baby is going to be born underweight. Now, all tissues of the body will be perfectly proportioned in size except one, which is its fat mass. So a premature baby is born with too little fat. And if you don't have a lot of fat, you don't have a lot of ketones being produced.
- RCDr. Rangan Chatterjee
Mm.
- BBDr Ben Bikman
And one of the reasons why that baby may develop, a premature baby may develop learning disabilities in life, and there is a much higher risk of that, it could be, and this is articulated in the work of Dr. Stephen Cunnane, a wonderful-
- RCDr. Rangan Chatterjee
Mm
- BBDr Ben Bikman
... gentleman and scientist, and I encourage everyone to look up his work. And much of what I'm articulating now is based on his theory of evolution that he articulates in his book, Survival of the Fattest. Uh, I admire the, the wittiness of the title here, but his whole theory is that humans are unique among all land-based mammals because we are the only singular, only land-based mammal born obese. We are born extremely chubby, and he posits that that chubbiness is essential to the, to the development of one single organ that arguably makes humans different from every other species, which is the brain, that ketones are the preferred fuel for the brain. And then maybe come back to that thought, lest people still are holding on to some outdated view of ketones being a problem. We have a view which even persists in academia. I have colleagues-
- RCDr. Rangan Chatterjee
Mm
- BBDr Ben Bikman
... who state this with conviction, teaching students. They will say, "The brain prefers glucose," or, "Glucose is the preferred brain fuel," and that is demonstrably false. The m- You can take an individual who has glucose levels at five millimolar and ketone levels atLet's say two and a half just for easy math, where the ketones are less than half the concentration of what the glucose is, and already in that state, the brain is obtaining 70% of its energy from the ketones.
- RCDr. Rangan Chatterjee
Mm.
- BBDr Ben Bikman
So how can we reason that the glucose is the preferred fuel when even at half the level, the brain is already getting more than twice of its fuel, uh, from the ketones? And, and so ketones are an essential fuel for the brain, helping the brain even develop, and this is likely why newborn humans get into a deep state of ketosis so quickly. Within just one to two hours of fasting, the baby is in a deeper state of ketosis than-
- RCDr. Rangan Chatterjee
Wow
- BBDr Ben Bikman
... its parents are after a full day of fasting. So we cannot pretend, or we shouldn't say that ketosis is an unnatural state, a state of having elevated ketones. But we make them. All of this was a very long-winded, winding answer to, um, just w- are ketones a sign of fat burning? Yes, absolutely they are, but they go much further than that. But I, I... As much as the evidence on ketones is growing, and my own lab has published some fascinating, I, I'd like to think, work on ketones and the signaling, ketones are now known to be so beneficial to the brain, including not only seizures and migraines, where that evidence has existed for over a, a century, but also with things like cognitive decline, early-stage Alzheimer's disease, Parkinson's disease-
- RCDr. Rangan Chatterjee
Yeah
- BBDr Ben Bikman
... migraines, I, I mentioned improves with ketones. Uh, the... There was a paper just published on women with PCOS where just supplementing ketones, and that gets me to my point, that if a person wants to get some of the advantages of ketones, and there, there are many. We published a paper using humans, finding that when ketones were elevated, the metabolic rate of their fat tissue was three times higher than the metabolic rate of humans that did not have elevated ketones, so they can help directly with weight loss by enhancing metabolic rate. Uh, but this is what has given and justified the explosion in research and interest in products in exogenous ketones, but I'm going a little outside the topic. So biochemically, we make ketones when we burn fat. They are not only a fuel for the body, especially the brain, but every cell with mitochondria will use ketones as a fuel very happily.
- RCDr. Rangan Chatterjee
Yeah.
- BBDr Ben Bikman
But the brain especially. But then ketones have direct signaling effects that benefit the body, reducing inflammation, improving mitochondrial function, and that's why some people may want to, in some instances, just be drinking ketones as well.
- RCDr. Rangan Chatterjee
Yeah. So you're not necessarily saying people need to adopt what is traditionally called a ketogenic diet, right? I think there's a subtle difference here whereby you're saying most people, if you're metabolically well, if you have a period of time without food, maybe 12, 14, 16 hours, you will be making ketones and you will be burning fat. Okay? You're also saying though that, and I know you recognize this from hearing you talk in, uh, other podcasts, that a traditional ketogenic diet can be quite tricky for some people-
- BBDr Ben Bikman
Mm-hmm
- RCDr. Rangan Chatterjee
... to stick to. And you're saying now that the development of these exogenous ketones is a way for people to not have to go on restrictive ketogenic diets, but still get some of those benefits. Now, that's super fascinating. Now, I have been following the research on exogenous ketones for a few years. I myself have probably been taking them on and off for about 18 months now. And what's kind of really interesting for me, Ben, is that I find you can often get ahead of what's going on in the literature by following what the top sports teams are doing, right?
- BBDr Ben Bikman
Yeah.
- RCDr. Rangan Chatterjee
'Cause they tend to not do stuff that doesn't work, right? They're looking for those marginal gains, and I'm well aware that for many years, the top Tour de France teams, many of them have been using exogenous ketones during the Tour de France. And I believe initially it was kind of, you know, no one wanted to share with anyone else that they were doing it as a performance advantage, but I think it's got out now where pretty much all of them, or at least a lot of them, are doing so. I'm also very good friends with Dale Bredesen, and I've been out before, uh, to California pre-COVID to help Dale run some intensives for patients with cognitive decline, and using his protocol, how one can actually reverse that in certain cases. And Dale is also a fan. So Dale is Professor Bredesen. He, I think, published the first study globally showing that certain stages of cognitive decline could be reversed by taking this multi-pronged approach, and one of the things that Dale will use with patients are exogenous ketones. So I think there's enough evidence now to say, hey, listen, for some people... And, and, you know, as I say this, Ben, I've just presented to you two very different extremes of the spectrum, haven't I? I've said about the Tour de France cyclists who are looking for elite performance, and I'm then contrasting that with an elderly patient with early cognitive decline who may benefit from taking exogenous ketones. Again, sort of mirrors the start of this conversation where I said to you insulin resistance seems to play a role in all of these different kinds of diseases. Again, we see a similar thing here with exogenous ketones. There is research suggesting that taking these exogenous ketones could help with a wide variety of different things. So, you know, when did you first become aware of the benefits of exogenous ketones, and who do you think should consider taking them to improve their health and wellbeing?
- BBDr Ben Bikman
Right. I first became aware of them when I, a, a little before, about a year or two before we published our report on ketones and fat metabolism. And that study is one of the ones I'm most proud of because we used all three biomedical models. We studied fat cells, we studied fat from rodents, and then we studied humans at the very top of it all. And, uh, in every model, the data were consistent how ketones enhanced or increased the metabolic rate of fat tissue by, uh, an, more than an insignificant degree. It was very meaningful. And, and so I think, uh, so that's probably within 10 years or so, I, I learned of exogenous ketones. And everyone who's curious about them, you really need to look at the work of Dominic D'Agostino-
- SPSpeaker
Mm-hmm
- BBDr Ben Bikman
... at University of South Florida. He is the, uh, I consider him the authority. Now, there may be are other authorities of ketogenic diets, but when it comes to ketone biochemistry and supplements, Dom is the authority. And I am-- I feel inclined to just encourage people who are curious about this, and I'll, I'll answer that second part of the question, which is who, who should be curious enough to ex-experiment, that make sure what you, what you th- what you are getting is in fact a ketone. That there are some things that people call ketones and, and they're actually more accurately termed an alcohol precursor, where it's an alcohol molecule that when consumed, the liver will convert it to a ketone. And, and that can have the-- I think there's, there's some considerations there that sometimes get glossed over. So if a person is interested in ketones, get just real ketones. Get beta-hydroxybutyrate in its actual form. Beta-hydroxybutyrate is the main ketone in the blood, and you can get, uh, exogenous supplements that are in fact just BHB or beta-hydroxybutyrate in what's called the salt or acid forms. They're both great, and they both work, uh, very, very well. And there's no, there's no need to convert it. Now, who should be curious enough to experiment with this? We mentioned a couple instances here where elite athletes, in fact, even we don't need to look f- I don't need to look very far. Even here at BYU, my university, we just had the, uh, the great glory of winning a, a national championship. Everyone listening probably knows in the US, collegiate sports is a very big deal. And we just have had this remarkable feat of our, both our men's and our women's cross-country teams won the national championship. So a huge accomplishment for the university. And interestingly-
- SPSpeaker
Congratulations.
- BBDr Ben Bikman
Thank you very much. W- I'm very, very pleased with these student-athletes. They, they use exogenous ketones. And, uh, and, uh, we-- someone would say, "Well, wow, what a coincidence." Maybe. Maybe, but also there's a performance advantage. So one person who would benefit from ke- exogenous ketones is the athlete who has a training and dietary regimen that has them eating a lot of carbs because they wanna have a lot of glycogen in their muscles and liver. And then that means they may not have a lot of ketones. And so more and more of these athletes want this extra fuel that they would normally be deprived of. Then anyone with any degree of neurological disorder, the evidence is just overwhelming.
- SPSpeaker
Mm-hmm.
- BBDr Ben Bikman
Schizophrenia, bipolar disorders, I mentioned Parkinson's, Alzheimer's disease, migraines, seizures, every one of those has evidence to show an improvement when the brain is able to access ketones, every one of those disorders and, and more. That whole realm of metabolic psychiatry is exploding. Speaking of the brain, there's just been new evidence looking at the effects of ketones on concussions and-
- SPSpeaker
Mm-hmm
- BBDr Ben Bikman
... and traumatic brain injuries, how ketone-- Part of the disruption and consequences of the brain impact is actually a disruption in glucose metabolism as well. So all the more reason to give the person a fuel that the brain can use, and the evidence shows faster improvement when you give the patient ketones. And then even as I mentioned with something like weight loss and fasting, part of the adaptation to being able to fast is, is your brain being able to use ketones for a fuel. Because if your brain is still trying to only burn blood glucose, it will transition poorly into a fasted state. And so some people find that exogenous ketones help train their body to fast more easily. And so then when they want to go into a true twenty-four-hour fast, they're able to do so much more readily.
- 1:51:39 – 1:59:20
Context matters: biomarkers, processed foods, high-carb healthy populations, and stress/sleep drivers
- RCDr. Rangan Chatterjee
knowledge of the science and research in this area. Practically speaking, you mentioned about doing things that can help us keep those insulin levels down, which of course will have a secondary effect of keeping our glucose levels down. There are lots of different diets out there that people like to debate about and fight about. Where I'm landing on this, you know, what, twenty-three and a half years since I qualified as a doctor, is that if you're mostly following a whole food diet, you know, mostly whole foods, minimally processed as much as you possibly can, then if certain blood biomarkers are in the normal range, so a fasting insulin under six, an HbA1c maybe under five point four, even under five point two, a good triglyceride to HDL ratio, so under one point five, then in some ways, the debate over the diet is semi-pointless in the sense that whatever you're doing in the context of your life is keeping your insulin and your sugar where you want it to be. Would you agree with that, or would you see it slightly differently?
- BBDr Ben Bikman
I would agree one hundred percent. Yep. I, I've never-- as, as much as I make-- I come across very strong in my language sometimes. My wife tells me that often. But I, I would never want to have conveyed that there's only one way to do this.
- RCDr. Rangan Chatterjee
Hmm.
- BBDr Ben Bikman
Uh, I think there, there are multiple routes to getting to the same destination. And, and I want there to be, uh, I like that there can be variety because of, say, the cultural differences, the, the traditions, the, the-- even if it's sort of self-imposed moral views, um, uh, I, I, I like that we can come, we can have different, uh, routes to the same destination. And yes, if the metabolic outcomes, the cardiometabolic markers are all good, then I would say that person's probably doing something that works. Now, m-maybe they're able to get away with something because of high physical activity levels that later they will need to reconcile. Uh, so, so I don't think just having optimal numbers does not mean what you're doing is going to be the way you should continue to do it. I think that's very important, that if I-- You know, I'm a college professor, and I can see young twenty-year-olds who do all kinds of abusive things to their bodies when it comes to lifestyle. They eat terrible things, they have terrible sleep habits, and yet their metabolic markers-
- RCDr. Rangan Chatterjee
Hmm
- BBDr Ben Bikman
... would generally be all quite good. Well, let's see what happens in ten years from now.
- RCDr. Rangan Chatterjee
Yeah.
- BBDr Ben Bikman
So we shouldn't, we shouldn't use the metabolic marker to justify poor habits if, if we can acknowledge them as such.
- RCDr. Rangan Chatterjee
Yeah.
- BBDr Ben Bikman
But all things equal, if we took a group of fifty-year-olds across various ethnicities with various dietary and lifestyle habits, and their metabolic markers were good, then I would generally just say, "Well, then keep doing what you're doing." At that point, there would be a consequence. We would see the negative signs already.
- RCDr. Rangan Chatterjee
Yeah.
- BBDr Ben Bikman
And so I think there is room for variety, and as you and I have already stated, I think there would still be some common things, even though some would be more meat-based than others, let's just say, as an obvious difference. Uh, I, I think what they would still have in common would be the avoidance of, of particularly processed foods.
- RCDr. Rangan Chatterjee
Yeah. What's really interesting is I adopt a very similar approach to you in my own life. I've experimented enough to know what works for me, what doesn't work for me, particularly as I get older, you know, and I'm constantly tweaking and, you know, of course, given what we do, we're fascinated by health. I'm fascinated by population health. I'm also fascinated by what I can do to keep myself well as I get older.But what's really interesting is although we will adopt a similar approach ourselves in the environment in which we live, I find it really interesting to think about other populations who are seemingly very insulin sensitive, yet doing some quite different things. So I guess one example might be the Tsimane tribe, that's T-S-I-M-A-N-E, who are known to have 70% carbohydrate diets and very low rates of chronic disease. First of all, are you familiar with the research on the Tsimane tribe? Um, and, and if not, all I'm-- the only point I'm trying to make is that, um, I think you can't really look at your diet in isolation. You sort of have to look at it in the context of everything else that's going on in your life. So in my first book, about seven, eight years ago, I, I hypothesized that could it be in this modern Western environment where people, um, are under-moved, under-slept, chronically overstressed, living indoors, and find it hard to get cheap, accessible whole foods, could it be in this particular environment that a low-carb diet appears to have such incredible benefits for so many people? Whereas, I'm not an expert on the Tsimane tribe, to be clear, but whereas the Tsimane tribe may be living outdoors a lot more, getting exposed to a lot more natural light, have the proper circadian cues from their environment, low levels of stress, strong community, active, maybe fifteen, sixteen thousand steps every day. Maybe in that environment, they can have a seventy percent whole food carbohydrate diet, yet still have low insulin levels and be highly insulin sensitive. Uh, any comments at all, Ben, on what I've just said?
- BBDr Ben Bikman
Yeah. Yeah. Yeah. So I wasn't familiar with the Tsimane, but I'm familiar with other groups like, say, the Kitavans, where decades ago they were pointed to as a group that ate high carb and yet had very low levels of cardiometabolic complications. So I've certainly been familiar with this sort of community, and I think you've articulated it well, and I have very little to add, and maybe just then I will reiterate in my own brief way. I think you can make up for a lot, and you need to account for a lot. I like that you mentioned stress. These are probably cultures that have incredibly good sleep habits. And good sleep can make up for a lot.
- RCDr. Rangan Chatterjee
Mm.
- BBDr Ben Bikman
One thing we haven't even discussed is the role of stress as a driver of insulin resistance, where when I first articulated the fast insulin resistance and with high insulin being the main one, well, there are two others that, uh, I haven't really mentioned. Inflammation is an acute stress that causes insulin resistance, and then the stress hormones themselves, c- cortisol and epinephrine, cause insulin resistance very quickly. And then the most common reason that cortisol will be up is going to be poor sleep. So the more-- Yeah, I think it is dangerous to extrapolate beyond these cultures and communities where we need to take their diet in the environment that it's in. And, and you said it well, very physically active and, and probably v- much lower stress environments where strong sense of community as well plays into that, and then really good sleep habits, and then avoiding these more processed, you know, sugars and other refined, more versions. The carbs they are eating are in whole forms.
- 1:59:20 – 2:11:23
Personalization and next levers: visceral fat, adrenaline, cold immersion, and a ‘breakfast tomorrow’ action step
- RCDr. Rangan Chatterjee
Yeah. And just to tie up a loose end from early on in this conversation, when we were talking about our respectively different ethnicities and how in a very similar environment with a similar caloric intake, we're going to likely store fat in a very different way. We've gone through that, but then can we extrapolate from that, that me and you therefore might need a slightly different approach to lose that fat and improve our metabolic health? Because we store it differently, do we need to attack it and address it differently?
- BBDr Ben Bikman
Hmm. Yeah, that's a good question. I, I think the, the easy answer, the easy answer to the degree to which different people who store fat differently need different interventions is no, that the-- generally, the same principles will apply, f- foremost being lower insulin. That is the one common variable. Lower insulin to enable fat burning while being prepared to control calories, and I think the best way to do that is through structured fasting. However, that is not to say there aren't-- isn't some nuance. For example, if a person has more of their fat stored viscerally, visceral fat is, is much more responsive to the fat-burning hormone epinephrine, or adrenaline, as we-- you'd say in the UK. Uh, adrenaline is going to increase fat breakdown much more rapidly, more easily at visceral fat cells than subcutaneous fat cells. And so you had described some of the men you were encountering growing up, how they were quite thin on their limbs and quite chubby right on their belly. That is one of the more common ways to describe someone with more visceral fat. Now, why am I even bringing that up? There are interventions that will increase epinephrine a little more, like cold immersion, like exercise. So cold therapy, you know, getting in the ice bath, that will increase epinephrine substantially. Exercise increases epinephrine. So visceral fat m- may be more responsive to that kind of intervention than someone who has more, say, subcutaneous fat, where the subcutaneous fat is less responsive to that-... burning breakdown signal of the epinephrine and adre- or, or adrenaline. So I don't mean, while I do think there are common principles, like generally lowering insulin, and, and so being smart about the composition of the calorie, less so the quantity, at least initially. But then maybe complimenting that, depending on your unique phenotype, your unique version or method of storing fat, then you may benefit from high-intensity interval training, where you have a, a substantial adrenaline burst.
- RCDr. Rangan Chatterjee
Mm-hmm.
- BBDr Ben Bikman
Or one thing that I'm very passionate about is cold immersion. I, I personally, I, I love it and do it every single morning, and am now at the point I can't imagine starting my day without it.
- RCDr. Rangan Chatterjee
Wow. It's kind of interesting. I [laughs] I certainly don't wanna start off down a new rabbit hole, given the time. I mean-
- BBDr Ben Bikman
Yeah [laughs]
- RCDr. Rangan Chatterjee
... there's so, there's so many things that I wanna go into with you. I think I'll save some of them for a part two, th- like stress, inflammation, supplements, things like berberine, ALA, apple cider vinegar, the effects of plastics on insulin resistance, medications that make us more insulin resistant, uh, cancer, fasting, fast-
- BBDr Ben Bikman
Well, and we even have evidence showing that diesel exhaust particles force fat cells to grow.
- RCDr. Rangan Chatterjee
Yeah, exactly, so-
- BBDr Ben Bikman
You know, so even, even outside calories entirely, yeah.
- RCDr. Rangan Chatterjee
I, I think I've already got a list there which will make a really good part two. Just to finish [laughs] off this part one, um, cold immersion, again, I'm also fascinated by some of the research. I, I think the psychological benefits, of course, are profound when we do something uncomfortable and learn to control our response to that.
- BBDr Ben Bikman
Well, well said.
- RCDr. Rangan Chatterjee
You know-
- BBDr Ben Bikman
I like how you just said that. Well said
- RCDr. Rangan Chatterjee
... a- and also, of course, there can be these biochemical benefits as well, uh, for certain people. But again, what's really interesting is I hear you talk about your own relationship with cold immersion. I think back to ethnicities and cultures, and then I think, well, I, I can argue this two ways. I could argue that, well, my ancestors largely lived in warm equatorial environments, where food was probably relatively abundant most of the year round. Uh, didn't have to, you know, overeat in the summer to store fat to get through a long, dark winter. How often would they have been exposed to cold?
- BBDr Ben Bikman
Never.
- RCDr. Rangan Chatterjee
Yeah. Well, unless they live in the mountainous regions, of course.
- BBDr Ben Bikman
Yeah.
- RCDr. Rangan Chatterjee
But then you can also flip it. You know, I'm very fascinated by a lot of the work from people who talk a lot about circadian biology, and my understanding is that in more Northern Hemisphere climates, there's an incredible benefit to having cold immersion. And then I think about me, and I think, well, my genetics and my biology is probably designed for an equatorial environment, but I live in the northwest of England. So then I'm thinking, do I try and live like my ancestors, or might cold immersion help me in the context of my new environment?
- BBDr Ben Bikman
Hmm.
- RCDr. Rangan Chatterjee
And I'm not expecting you to necessarily have an answer-
- BBDr Ben Bikman
Yeah
- RCDr. Rangan Chatterjee
... un- unless you do, of course. It was more just to hypothesize on these various different elements that can be either very confusing or actually quite empowering as well.
- BBDr Ben Bikman
Yeah. I, I think this could be an instance of, um, not... You know, earlier we had mentioned a similar conundrum with regards to high insulin and high ketones. I, I think that this could be another instance of us saying, let's not let an evolutionary view prevent us from taking advantage of-
- RCDr. Rangan Chatterjee
Mm-hmm
- BBDr Ben Bikman
... an intervention. Uh, so y- I like that you mentioned the mental health. When I first became interested in ice baths, it was actually to try to improve some modest levels of anxiety, very controllable, but I just tend to be a kind of high-strung, um, um, uh, person. I'm always kind of on, and I just would have a hard time being calm and quiet in my mind, and even just tapping my toes all the time. N- not to mention, just very poor sleep habits. And I th- when I started this last winter, I wondered at the improvements in my sleep, and I wondered whether a part of it was the fact that here in the Northern Hemisphere, even worse, actually, in the UK than where I am in Utah, that sun doesn't rise until late in the day. And especially in the UK, even if it does rise, there may be so much cloud coverage that you still don't really see it.
- RCDr. Rangan Chatterjee
Mm-hmm.
- BBDr Ben Bikman
And you don't have that exposure, that sunlight hitting the eyes, telling your body, "I'm awake now. It's time to start my clock." And when I would wake up in the very early morning and get into that ice bath, I, I, I can't quantify this, but I swear that, by this, that it told my body, "I'm awake now-
- RCDr. Rangan Chatterjee
Mm-hmm
- BBDr Ben Bikman
... and it's time to start the clock." So that by the time the evening would roll around, I would be much more tired.
Episode duration: 2:11:24
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