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How Food, Fasting & Lifestyle Can Transform Your Metabolic Health & Reduce Your Risk of Disease with Dr Ben Bikman #582
02:17:05
Most of us will never have our insulin levels tested, yet this single hormone is the body’s master regulator of energy. When it stops working properly, almost every system in the body is affected, from how we store fat, to how we age.
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- [00:01]
Dr. Ben Bikman
Skin is a window to the metabolic soul There are two specific problems that are surprisingly connected to insulin resistance and conveniently both of them occur in generally the same places. So along the collar line of the neck is the most common sight. And I bet as I describe this people will begin to nod their head thinking, oh, I've seen that before.
- [00:25]
Dr. Rangan Chatterjee
Hey guys, how you doing?
- [00:27]
Podcast Host/Announcer
Hope you're having a good week so far. My name is Dr. Rangan Chatterjee and this is my podcast Feel Better Live.
- [00:35]
Dr. Rangan Chatterjee
More Most of us have never had.
- [00:39]
Podcast Host/Announcer
Our insulin levels tested, yet this single hormone is the body's master regulator of energy if it stops working properly. Almost every system in the body is affected, from how we store fat to how quickly we age. Today's guest is Dr. Ben Bickman, a scientist and world leading expert and on insulin and metabolism. He's a professor in the Department of Physiology and Developmental Biology at Brigham Young University and has spent years researching how changes inside our cells lead to common metabolic disorders such as obesity, type 2 diabetes and dementia. He frequently publishes his research in peer reviewed journals, speaks at scientific conferences all over the world, and is the author of two books, why We Get Sick and How not to Get Sick. In our conversation we discuss why insulin is the body's master hormone, guiding how we store and use energy and how.
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Dr. Rangan Chatterjee
Resistance to it can cause a wide.
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Podcast Host/Announcer
Range of chronic health problems.
- [01:50]
Dr. Rangan Chatterjee
The fact that almost nine in 10.
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Podcast Host/Announcer
Adults show signs of poor metabolic health. How ethnicity and genetics shape the way we store fat explaining why two people of the same weight and size can face very different risks of conditions like type 2 diabetes or heart disease why focusing only on blood glucose misses the early warning signs of poor metabolic health and why measuring insulin levels offers a clearer and earlier picture of risk. The visible clues your body may already be giving you that can indicate elevated insulin and practical strategies to bring insulin down, from reducing refined sugars and starches to spacing out meals and experimenting with fasting in ways that work for both men and women. So often we're told that chronic illnesses are inevitable or a natural part of aging, but this is simply not the case and this conversation is a powerful reminder that our everyday choices have a profound impact on our short term and our long term health.
- [03:11]
Dr. 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?
- [03:56]
Dr. 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 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 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 nour 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.
- [06:36]
Dr. 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. Back in 2015 and I filmed this in 2014, I filmed the very first documentary globally to show that a condition called type 2 diabetes could be put into remission in just 30 days. And, you know, it's crazy to think that was 10 years ago now and it was deemed 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, those terms don't really land with them. I think in the same way.
- [07:37]
Dr. Ben Bikman
Oh, I fully agree. In fact, 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 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 difficult to help people appreciate that insulin is the master metabolic hormone and that when it's not working well, diseases will follow.
- [08:20]
Dr. 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.
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Podcast Host/Announcer
Try and address this, are you able.
- [08:34]
Dr. Rangan Chatterjee
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 good to get an understanding of how large is this problem, but then also what is 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.
- [09:10]
Dr. Ben Bikman
Yeah, 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 within the United States. I can start there and then start to extrapolate a little bit because I think some of the data starts to get a little bit murky within the United States. The problem is sobering. Where a report was published in 2016 here which did a national survey to try to understand the prevalence of the metabolic syndrome. And they found that 88% 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, hyperglycemia, hypertension, and then I guess I could call the last two just dyslipidemia, low HDL and elevated triglycerides. So that five part problem is what constitutes the metabolic syndrome. Again, at least one of those was found in 88% 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 it is a superior term because it's more precise. It doesn't quite have the ring to it like metabolic does. So it might not sound as good, but this suggests that 88% 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 also fat. Well, interestingly and even somewhat paradoxically, while Americans are certainly quite fat and we're, I think, in the top 10, although not the fattest, but we're up there, we are not even in the top 70 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 70s, 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're able to look at type 2 diabetes, which is a more clearly defined clinical situation than insulin resistance, and we can revisit that later, insulin resistance just isn't measured 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, the Middle East. 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 about as bad, if not worse, in many countries around the world and even in ways you wouldn't expect. 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 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 10 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. 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 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 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 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 they're fasted, insulin 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 see lower 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 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 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. 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 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, 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 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 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 effects 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.
- [18:41]
Dr. Rangan Chatterjee
Yeah, 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 has poor metabolic health. And you mentioned a very alarming statistic in America. 88% 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 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 going to 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 the 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 summary of where we are so far?
- [21:00]
Dr. Ben Bikman
Yeah, yeah. In fact. And then just to finish that thought, or to tag onto that thought, my own ancestry Primarily came from England. Ironically, where yours went to, mine came from. And so you and I do represent two very beautiful examples of the ends of the spectrum. So if you and I both gained 10 pounds of pure fat, genetics would suggest that I would simply just be that much chubbier 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 going to have consequences of insulin resistance. And just to put a fine point on that, there was a study done 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 as well, where they removed a small portion of abdominal fat. And remember, these men looked the same. So if you 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, with diameter over three times the diameter. And that's just the diameter when you look at the volume, that is multiples maybe 10 times larger of a fat cell. Even though the men were the same fatness and body size, overall, they were. 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, on average. Now, one other point of nuance where you described what would have created that fat mass in the first place. Yes, calories matter, 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, 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 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 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, but so too does insulin in telling the body, especially the fat cells, what to do with those calories.
- [24:33]
Dr. Rangan Chatterjee
Yeah, let's just stick on this example using you and me, because I think it's given our respective ethnicities, 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.
- [24:54]
Dr. Ben Bikman
You know.
- [24:55]
Dr. Rangan Chatterjee
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, Ben, if we were the same height and we were the same weight and we had similar levels of high insulin, 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, 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 could basically be fat, but metabolically well. And I could be the opposite. I could have the same BMI as you, but because of my ethnicity, I'm not going to make new fat cells. I'm just going to use my existing fat cells and stuff them full of fat. They're going to expand, they're going to start leaking out inflammatory markers all around the body, whereas you are going to make new fat cells and they're going to all be small and tight. So you're going to look fat, perhaps, but the markers for long term health are going to be significantly different with you. Is that accurate? The way I've sort of articulated it?
- [26:56]
Dr. Ben Bikman
Yes, yes, perfectly. I would just add one final comment, that this whole concept, when it was first posited in maybe its clearest form, was described as the personal fat threshold. 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, it's very, very likely that the average South Asian, for example, has a variant that is of a gene called Ppar gamma and where PPAR gamma is the main gene regulator that determines the birth of new fat cells. This has been shown to happen across ethnicities where the PPAR gamma is a less active variant, whereas in, say, Caucasians, PPAR gamma is quite active. And people can actually see this at a broad level. If anyone's ever curious to go and wants to have sort of a morbid evening of entertainment, you can look for TV shows about individuals who have gained just super human 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. It would be extremely unlikely to find a South Asian. 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.
- [28:59]
Dr. Rangan Chatterjee
Yeah. It's kind of interesting if I reflect on my childhood and a lot of my parents friends offer similar backgrounds, 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 see that belly protruding out more and more, which is kind of interesting, which kind of plays in here to what you're saying. 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?
- [29:59]
Podcast Host/Announcer
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- [31:47]
Dr. Rangan Chatterjee
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- [31:48]
Podcast Host/Announcer
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- [34:04]
Dr. Ben Bikman
Right, right. Well, this, this theory can only go so far as, as so many theories when it comes to evolution can. 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 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 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, let's say closer to the north 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 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, you need a little, you're not only protected from the sun, you're going to get sunburned much less readily than I am, but you also need a little more direct light to make sufficient vitamin D 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 want to have the ability to store a lot of fat in the event that winter comes in and I'm not able to eat for a month or more and I have to just survive on water or weeks, maybe a month is dramatic. But where your ancestors would have been closer to the equator, you have much more direct sunlight. You're protected more from the sun. You don't need the insulation 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. And so you aren't as needed, you didn't have to adapt, perhaps to as much scarcity.
- [36:13]
Dr. Rangan Chatterjee
Yeah, it's fascinating, isn't it, when you think about these adaptations 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 listen to this show. I hope by now are aware of insulin resistance, but the problem 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 around, 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.
- [37:23]
Dr. Ben Bikman
Yes, I think this is such an important point because it helps us understand why the problem has become 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. Our glucose centric paradigm has caused us to miss the more relevant marker. 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 50 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 good 10 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 10 days. But even historically, through India, through China, through Western Europe, the main manifestation 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 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. So we can forgive the historical focus on glucose, but again, I think it's becoming less forgivable 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. But 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 2 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 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 glucocentric 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 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.
- [42:45]
Dr. 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. 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 that 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 the companies 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.
- [44:44]
Dr. Ben Bikman
Right? Yeah. Yes. Skin is a window to the metabolic soul. It gives us some insight where we can't maybe get that blood marker which is going to 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 collar line of the neck is the most common site for both of these problems that I will articulate. 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, 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, 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. Its healthier state. So these are not permanent problems.
- [47:12]
Dr. Rangan Chatterjee
Yeah, well, 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 kind of 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. Where would you start to advise people on that?
- [47:58]
Dr. Ben Bikman
Right, yeah. This is in fact the good news of all of this. As much as our conversation, in 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 explored the reversal of type 2 diabetes in as little as 30 days for what is 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. If 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 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 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 many fasts, 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. 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 little preschool children who get hungry in two hours. As adults, in fact, as adults, we should be able to fast for 24 hours without much effort. In fact, if a person cannot fast for 24 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 24 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 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 people have, of course, because of our calorie centric view of obesity, they tend to have a calorie centric view of weight loss. I think calories matter, but I would recommend that people start with a low insulin strategy, because if you lower insulin, 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, lower metabolic rate can go up by almost 400 to 500 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 1,000 calories a day by just keeping their insulin down, depending on where they're starting. 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 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 energy 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 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.
- [54:24]
Dr. 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 24 hours. Now, the crazy thing is, Ben, is in 2025, 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 24 hours without having any food and we couldn't function and we got really sick, and I'm not convinced many of us would have survived.
- [55:09]
Podcast Host/Announcer
Right.
- [55:09]
Dr. Rangan Chatterjee
So, 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 24 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 sectors is more biased to being able to fast for 24 hours?
- [55:41]
Dr. Ben Bikman
That's a great question. And it's a topic that's getting 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 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 carries quite a punch. 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 meaningful effects that I think would make it harder for the woman to fast during that, especially that week or so before the progesterone starts to come back down of the luteal phase. So the time after she ovulates. 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 doing so. And thus, perhaps it would be a time to be a little more generous with yourself 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 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 the body wants to prime itself to be hungry. And so in the event 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 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 40% 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 size of fat cells explain the differences in cardiometabolic risk. A premenopausal woman is virtually immune to the consequences of having higher fat mass because she has just more but smaller fat Cells. But 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. But that's a bit of a branch in topic here. But this all sort of touches on this concept of metabolic flexibility, 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 Pittsburgh, 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 transition into the fasted state and they go into fat burning mode. And 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 diesel engine that can take you very far metabolically down the road. But. But some people are metabolically inflexible, as it was identified by Goodpastor 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 2,000 calories stored as glucose that it can share with the body. And so if you have a hard time 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, if we're not tapping that fuel, then what good is it? 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 24 hours. I just start to feel so sick. I thought it's because you're stuck in sugar burning mode. You've never allowed your body. 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 still cannot step too far away from insulin.
- [61:46]
Dr. 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 use 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 their periods and just sort of say when those phases are 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.
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- [64:45]
Dr. Ben Bikman
Yeah, let's bring that down to more kind of palatable language. Yeah. So right at the beginning of the early part of the cycle, 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's the ovaries that are producing these hormones that are not only telling the uterus what to do, but also telling the body what to do 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. Sorry, the follicular phase, we're developing follicles 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. 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 that now determines the luteal phase, which is 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 200 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 she's going to 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, 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 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 in 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. 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 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've 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.
- [69:24]
Dr. Rangan Chatterjee
Yeah, I love that. So that's, I hope, really helpful for people, particularly for women trying to understand why they may crave certain things, they may find things, 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. Probably not quick enough 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 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 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, you're a big fan of changing your breakfast away from the modern sugary cereal, high insulin promoting breakfast to the more prioritized protein, have some healthy fats, and if you are going to 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 that term, low carb, I think again can be confusing because low compared to what? Right. 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?
- [72:19]
Dr. Ben Bikman
Yes, it is, but I would say I didn't use the words low carb on purpose. Where when I say control carbs, maybe another way of describing this would be a smart carb approach. Because after all, what if you. For me, that's not so difficult to do. My culture, my food culture, my Family dynamic, 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 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 just find prudent ways to do it. And I'll come back to breakfast in just a moment because I think 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 is maybe a culture that has more carbs in its diet than maybe any other because of just some avoidance of meat, which I am incredibly understanding for. That's why I mentioned these kind of cultural differences that we start to see. And yet I know many, many Indians who adopt a smart carb diet. 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, to be eating very low carb, very 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 meat based approach, an omnivorous approach, or even vegetarian, or 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 ultra processed foods. And 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, which is in their whole food form, and then to bring it back to breakfast. 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 maybe I'm looking at that from the perspective of a family man, 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 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. And so I want to have dinner with my family. So I choose to fast through breakfast because it is 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 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 6pm, 6 to 9pm Then all of a sudden this little gremlin comes to life inside their brain that makes it a herculean effort to deny themselves that indulgence. Even me, as much as I know, 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 application. That knowing something, and I would want to state this quite emphatically to anyone listening and with empathy. 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. 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 that are so abundant.
- [78:44]
Dr. 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 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 going to 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 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 in the day, I think there's some good Spanish studies, if you eat most of your calories before 3pm you have better metabolic outcomes even if you consume the same number of calories. You know, it's 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 over consume 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 I believe it's no longer in the house. Right. Is that right? It's still the same. You don't keep it in the house?
- [80:55]
Dr. Ben Bikman
Yeah. No, it's because it starts to call out to me, that, that. That siren call. It's like a sailor jumping overboard to drown himself. In my case, it's drowning in cereal.
- [81:06]
Dr. Rangan Chatterjee
Yeah. So I guess there are many ways we can try and lower insulin, right? You've mentioned a few already. Prioritize protein, increase healthy fats. Those things, by and large, don't tend to drive up insulin. 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. I've seen very few things help an individual understand the impact that food has on their body, like a cgm. Perhaps we can talk about the pros and cons of a CGM at the same time. I just want to 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 breathalyzer. They measure the composition of 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 1 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. So simply using that device helped reinforce in my head, hey, Rongan, 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 that earlier dinner was more important than the carb intake. When I actually compared the two, I would find that if I had my evening meal at, let's say, 5:00pm, 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 somebody you want to 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 what I just mentioned?
- [83:53]
Dr. 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 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 change. They don't like what they see, and 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 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 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 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. And ketones are, as much as we have perhaps a generally negative view. 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 is simply fat ketones are simply consequences of the liver burning a lot of fat. And that happens as insulin comes down. And so 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 I know I've had conversations with that group, and I love them as people. They just seem like really delightful people.
- [85:55]
Dr. Rangan Chatterjee
Can I just touch on a key point there? We'll come to ketones, because I'm fascinated by that topic around CGMs. For people who don't know, CGM sounds for continuous glucose monitor. And it is, you know, a real time 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 earlier 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, you know, a CGM could be really useful, can you just help people understand that? Because on one hand we're saying glucose is late, we want to 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.
- [87:11]
Dr. Ben Bikman
Right, Right. Yeah, I can see how that might seem a little incongruous. The value of the CGM is that it allows us to measure 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. But that's not to say glucose is irrelevant, because dynamic glucose can tell you the story. So if a person has a CGM and they eat a couple pieces of bread by following their cgm, they would want to see how high did it go? Did it go. I'm going to use milligrams per deciliter on this trade here with millimolar. I can't recall, but it would maybe be up to 8 or 9. Millimolar is going to be too high, but around 200 milligrams per deciliter. That's a warning. You went a little too high, higher than you should given what you ate. But then look at how long it takes to come down. If that hasn't come down by about two hours, that is again a warning sign. And then another warning sign can be what happens when it does come down? Does it come down too low? Do you dip into this hypoglycemic range? That itself a rebound. Hypoglycemia is itself a sign of too much insulin and a dysregulated insulin response. You know, all of this being some form, some manifestation of insulin resistance. So what we aren't able to get with A once annual fasted single point of glucose we are able to get by looking at glucose and all of its dynamic life cycle during the course of a day. So in that regard, CGM is powerful. But maybe one other final point, just to help people balance it off of the conversation from earlier. I think there is tremendous value in bringing in controlling glucose. But if the clinical intervention is to control glucose by pushing up insulin, that is not a trade off, that is worth it. It is a net harm. It is worse than otherwise.
- [89:15]
Dr. Rangan Chatterjee
And how might one do that? Because a lot of the dietary interventions will actually lower glucose and lower insulin.
- [89:22]
Dr. Ben Bikman
Right, Exactly. That's the difference where neither you nor I, we're not saying there's not value in lowering glucose, but conventional clinical care will tell the will give the individual a prescription for a drug that will lower the glucose by forcing the insulin up even higher and then even giving them the asinine advice of just eating whatever you want, continue to eat whatever you want, just cover it with your insulin. That is not what we're saying. We're saying if glucose is high or the frequent glucose excursions are what's driving your insulin up and keeping insulin up all day. Well, we need to lower insulin, but the way to do that is by just avoiding everything that's messing with your blood glucose so frequently and so control the consumption of carbohydrates that are resulting in these glycemic excursions, which are in turn resulting in insulin excursions as this comes down now. So the dietary approach actually does flip it on its head. Said in, in direct contrast to the clinical approach. The clinical approach will say we're going to push your insulin up higher to control your glucose and you will get fatter and die faster, but you'll have good glucose.
- [90:30]
Dr. Rangan Chatterjee
And you're Talking about type 2 diabetes where yes, got elevated insulin, you've got elevated glucose and you'll be given a prescription for insulin or you know, when it's advanced at least, which will push into. Yes, it will bring glucose down, you hope, but it will do that at a huge cost because the insulin is going up. And we know the problems with chronically elevated insulin. And you're contrasting that with a lifestyle.
- [90:54]
Dr. Ben Bikman
Approach on you with the lifestyle approach. We would then state, we would say, well, our end goal is still to lower insulin because that's the thing driving insulin resistance and all the chronic diseases that come from it. But to get there, we're gonna control carbs first, we're gonna control your glucose first. And that comes back to the dietary Approach, So the. The lifestyle approach. And again, these are lifestyle problems. And so if it's a lifestyle culprit, it must be a lifestyle cure. We cannot expect a pharmacological or a pharmaceutical cure to what is a lifestyle problem. It's not a pharmaceutical problem in the first place. These diseases of lifestyle, it must be a lifestyle solution. So we flip the paradigm and the directionality of it, and we say the end goal is to control your insulin. The best way to do that will be controlling the starches and sugars that are in your mouth in the first place. What's the content of them, and how frequently are you consuming them.
- [91:51]
Dr. 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 going to start measuring ketones soon. That's very exciting. You also mentioned that, you know, people may have a negative view of ketones. 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 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.
- [92:26]
Dr. Ben Bikman
Gonna go up 100% of the time. Yes. Yes. So ketones are proof positive of fat burning. Now, it takes a little time to get there. So. So the average adult, and just. I'm going to 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 about 16 hours or so of fasting, an adult should start to have detectable levels of ketones in their blood or 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 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 newborn baby will, or just a baby in general, an infant will, 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 it is, in fact, so essential to brain development 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. 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 Cunane, a wonderful 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. I admire 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 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. You can take an individual who has glucose levels at 5 millimolar and ketone levels at, let's say, 2 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. 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 from the ketones? 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 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 just. Are ketones a sign of fat burning? Yes, absolutely. They Are, but they go much further than that. But as much as the evidence on ketones is growing, and my own lab has published some fascinating, 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 century, but also with things like cognitive decline, early stage Alzheimer's disease, Parkinson's disease, migraines, I mentioned improves with ketones. 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 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. 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. 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.
- [98:21]
Dr. 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 other podcasts, that a traditional ketogenic diet can be quite tricky for some people 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. Because 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 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 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 well being?
- [101:44]
Dr. Ben Bikman
Right. I first became aware of them when I 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 in every model, the data were consistent how ketones enhance or increased the metabolic rate of fat tissue by more than an insignificant degree. It was very meaningful. So that's probably within 10 years or so, I learned of exogenous ketones and everyone who's curious about them, you really need to look at the work of Dominic d' Agostino at University of South Florida. He is the. I consider him the authority. Now, there maybe are other authorities of ketogenic diets, but when it comes to ketone biochemistry and supplements, Dom is the authority and I feel inclined to just encourage people who are curious about this. And I'll answer that second part of the question, which is who should be curious enough to experiment that make sure what you are getting is in fact a ketone, that there are some things that people call ketones and they're actually more accurately termed an alcohol precursor, where it's an alcohol molecule that when consumed, deliver, will convert it to a ketone. And that can have. I think 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 exogenous supplements that are in fact just BHB or beta hydroxybutyrate in what's called salt or acid forms. They're both great and they both work very, very well, and 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 far. I don't need to look very far. Even here at byu, my university, we just had the great glory of winning a national championship. Everyone listening probably knows in the US Collegiate sports is a very big deal. And we just had this remarkable feat of Both our men's and our women's cross country teams won the national championship. So a huge accomplishment for the university. And interestingly, thank you very much. I'm very, very pleased with these student athletes. They use exogenous ketones and someone would say, well, wow, what a coincidence. Maybe, maybe. But also there's a performance advantage. So one person who would benefit from exogenous ketones is the athlete who has a training and dietary regimen that has them eating a lot of carbs because they want to 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. 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 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 traumatic brain injuries. How ketones, part of the disruption and consequences of the brain impact is actually a disruption, 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 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 24 hour fast, they're able to do so much more readily. And again, it's because the brain isn't sensing any degree of energy deficit because it's been trained to use ketones as a fuel. And ketones become the main fuel to the brain in the fasted state. I mentioned the study on pcos. A paper was just published this week finding that one version of the ketone called LBHB, one of the enantiomers, increased cardiac output by 40%. And what was so shocking in that study is that it wasn't because of some, what's called inotropic effect. It wasn't because the heart was beating harder, which would perhaps be considered a negative in a person with some heart failure or hypertension. It was because of the afterload. The aorta and the vessels, the main arteries were all more dilated. And so the pressure that the left ventricle was beating against was much, much lower. And that is what allowed a 40% increased cardiac output. So every time the heart was beating, it was able to move 40% more blood, all because they had given, they had administered this particular form of beta hydroxybutyrate. So from top to bottom, the evidence just continues to stack up. We published a report finding that ketones undo the inflammation as a result of uric acid. So people with gout may be able to find some significant rapid improvement. And again, the evidence just continues to mount. And I'm optimistic that it's actually just going to continue to grow.
- [107:51]
Dr. Rangan Chatterjee
In regular human physiology, Ben, Ketones would typically only be present when insulin levels were low. Okay. I think that speaks to everything we've been talking about thus far. Keep your insulin low, encourage fat burning, you're gonna get ketone production. And what's interesting about exogenous ketones. So ketones, you know, that we're taking in from the outside, we're drinking basically, as opposed to endogenous ones that our body will make, that you can actually drink those ketones whilst having high insulin. So you mentioned athletes who might be consuming a lot of carbs. They might want their glycogen source to be as full as possible before they race and compete. And you're saying for those guys, there may be or there is a performance advantage for taking exogenous ketones. Which begs the question from me, if in inverted commas in nature, ketones would only do their job when insulin levels were low, do we still believe that they have a powerful effect in the presence of high insulin levels? Which seems to be less natural, if I can say it that way. Do you know what I'm getting at, Ben?
- [109:14]
Dr. Ben Bikman
Oh, oh. In fact, yes. This is a concern I articulated, in fact, years ago, thinking of the biochemistry and the endocrinology of it all, which is exactly how you're framing the question. It is unnatural to be, for example, eating a bagel and all of the hyperglycemia and hyperinsulinemia that would come from it while sipping on a ketone drink. Those two would not normally happen. It's a metabolic paradox. High insulin and high ketones. I actually attempted to use that as evidence to avoid exogenous ketones. And because my thinking was at the time, if you've elevated insulin, you're telling the liver to make fat, and then what's to stop the liver? Who's uniquely suited to do this? What would be stopping the liver from taking that bhb, that ketone molecule, and then sending it into this biochemical pathway of lipogenesis. And in fact, I had become quite convinced in my own cleverness that that was the case. And yet, in reality, the liver lacks the enzyme that is capable of doing that. And so, in the absence of that enzyme, that would allow that conversion of BHB into a new fatty acid molecule and then a triglyceride molecule. I can't think of any. I still wouldn't recommend eating the bagel in the first place. But there is no. I'm unaware of any evidence to suggest that even though it is a metabolic paradox, that doesn't mean it's a metabolic problem. And again, there is, I think, human evidence to support this. You'd mentioned athletics. That's an easy one where we would say, well, they're just burning all that fuel. But even in this study in women with pcos, they did not change their diet at all. They ate the exact same standard American high carb diet that they were eating at the outset of the study. And the only difference was the inclusion of the exogenous ketone and every biomedical marker got better. So I don't think we need to look too far and indeed, I don't need to speculate too much where we can rely on some of that evidence. But you're right in noting that it is an oddity that wouldn't exist in nature. But that is perhaps just an evidence of how clever we are, that we can in some instances still sort of hack our way, in this instance, to the better outcomes.
- [111:37]
Dr. Rangan Chatterjee
Yeah, and I love that. And this is, you know, human innovation. We're sort of figuring something out and going, hey, wait a minute. Well, maybe for those people who can't go onto a low insulin diet or won't, maybe they can still get some of those benefits. And one of the cases I see as there being real potential for this is in those cases of cognitive decline. Right. And actually a friend of mine, one of their elderly relatives, who I was helping out with a little bit, it's kind of interesting. It was very hard for them to change their diet to the point that I would have liked them to in terms of trying to help them. I know that for some people with cognitive decline, you know, ketogenic diets, low carb diets with a therapeutic window for fasting can sometimes be life changing. I've seen that time and time again. But for this individual, you know, I recommended that if they could afford it because of course, not everyone can. And we have to acknowledge that, you know, it's not in everyone's budget at the moment. Although I hope over time that will change. As more and more people see the benefits of exogenous ketones. I imagine in the next three, four, five years is prices will come down for that individual. Their feeling is that those exogenous ketones really did help them, their family member, with their cognition. Right. So that's kind of interesting. Is it? We know ketones can have a power effect on the brain for some people, particularly if they've got cognitive issues. And depending on the family environment around them, or if they're in a nursing home, there May not be the appetite or the ability to change one's diet. And, you know, I'd be excited to see more research there, but it's a fascinating area for sure. Would you still say, though, ideally, you can get those benefits by adopting this low insulin approach that you outlined earlier on in the conversation?
- [113:43]
Dr. Ben Bikman
Yeah, you can. I would say you can get most of them. Although I did mention one study that suggests that there would still be a benefit to supplementing. So I mentioned the LBHB study, which increased cardiac output by 40%. So potentially enormous relevance to people with heart failure and even athletics. Well, the body makes very low levels of L bhb. It's very modest levels. And so that would be an instance where if a person said, well, I just really want that 40% increased cardiac output. A ketogenic diet won't do that. That because most of the BHB we're making is in the D form which isn't eliciting that same effect. Now, the D form is eliciting all the other cognitive benefits that we mentioned and the muscle fuel, but not the heart differences. And some of the. There's actually growing evidence. I just sat through an unpublished. These are results that are not published yet, but a talk just two weeks ago outlining other brain signaling effects of lbhb. So as much as I think a person could get an enormous amount of benefit, it just by making the ketones with the ketogenic diet. You've already outlined all of the reasons why a person may find that difficult to do or just not want to do it. And even if a person did want to do it, you could still make the case and say, actually there's this other form of BHB that you don't make a lot of that you could benefit from, depending on what your needs are.
- [115:07]
Dr. Rangan Chatterjee
Do you take them daily?
- [115:09]
Dr. Ben Bikman
I do, yeah. And again, I recommend the BHB form. You can get these insults and acids. Don't let the word acid scare you, it's just suggested. It comes in just the pure BHB form and you can get the D and the L. And I use them at different times for different purposes, but I do. As much as I still adhere to a low carb diet, I am convinced enough of the data that I just want a little more.
- [115:34]
Dr. Rangan Chatterjee
Yeah, me too. And it's on and off when I take them. But although I forgot today I tried to take one about 30 minutes or so before. I have a podcast because this is is, you know, a long form show where we go deep and you Know, anecdotally I think it makes a difference, but of course I've seen the research as well. Okay, Ben, we've gone quite technical and quite deep throughout the conversation today, which is one of the reasons why I wanted to have you on the show because you do have such a complete 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, 23 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 6, an HbA1c maybe under 5.4, even under 5.2, a good triglycerides HDL ratio, so under 1.5, 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?
- [117:33]
Dr. Ben Bikman
I would agree 100%. Yep. I've never as much as I make, I come across very strong in my language sometimes. My wife tells me that often. But I would never want to have conveyed that there's only one way to do this. I think there are multiple routes to getting to the same destination and I want there to be. I like that there can be variety because of say the cultural differences, the traditions, even if it's sort of self imposed moral views. I like that we can come, we can have different 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. Now maybe they're able to get away with something because of high physical activity levels that later they will need to reconcile. 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 20 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, habits, and yet their metabolic Markers would generally be all quite good. Well, let's see what happens in 10 years from now. So we shouldn't use the metabolic marker to justify poor habits if we can acknowledge them as such. But all things equal, if we took a group of 50 year olds across various ethnicities with various dietary and lifestyle habits in 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. 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, I think what they would still have in common would be the avoidance of particularly processed foods.
- [119:45]
Dr. 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 and I'm constantly tweaking. And 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 Samani 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 Somali tribe? And if not, the only point I'm trying to make is that 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 hypothesized that could it be in this modern western environment where people are under moved, underslept, 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 Somali tribe, to be clear, but whereas the Somali 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 15, 16,000 steps every day. Maybe in that environment they can have a 70% whole food carbohydrate diet, yet still have low insulin levels and be highly insulin sensitive. Any comments at all, Ben, on what I've just said?
- [122:07]
Dr. Ben Bikman
Yeah, yeah, yeah. So I wasn't familiar with the Tamani, but I'm familiar with other groups like say the Kitavans where decades ago they were appointed 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. 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 I haven't really mentioned. Inflammation is an acute stress that causes insulin resistance. And then the stress hormones themselves, 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 it in the environment that it's in. And you said it well, very physically active and probably 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 sugars and other refined more versions, the carbs they are eating are in whole forms.
- [123:45]
Dr. Rangan Chatterjee
Yeah. And just to tie up a loose end from earlier 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 or 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?
- [124:30]
Dr. Ben Bikman
Yeah, that's a good question. I think that the easy answer, the easy answer to the degree to which different people who store fat differently need different interventions is no, that generally the same principles will apply, 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 isn't some nuance. For example, if a person has more of their fat stored viscerally, visceral fat is much more responsive to the fat burning hormone epinephrine or adrenaline, as you'd say in the us, uk, 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 may be more responsive to that kind of intervention than someone who has more, say, subcutaneous fat fat, where the subcutaneous fat is less responsive to that burning breakdown signal of the epinephrine or adrenaline. So I don't mean while I do think there are common principles like generally lowering insulin and so being smart about the composition of the calorie, less so the quantity, at least initially, but then maybe complementing 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 substantial adrenaline burst or one thing that I'm very passionate about is cold immersion. I personally love it and do it every single morning. And now at the point, I can't imagine starting my day without it.
- [126:54]
Dr. Rangan Chatterjee
Wow, it's kind of interesting. I certainly don't want to start off down a new rabbit hole, given the time. I mean, there's so many things that I want to get into with you. I think I'll save some of them for a part two, like stress, inflammation, supplements, things like berberine, ala, apple cider vinegar, the effects of plastics on insulin resistance medications that make us more insulin resistance, cancer, fasting.
- [127:21]
Dr. Ben Bikman
Oh, and we even have evidence showing that diesel exhaust particles force fat cells to grow.
- [127:25]
Dr. Rangan Chatterjee
Yeah.
- [127:26]
Dr. Ben Bikman
Even outside calories entirely.
- [127:27]
Dr. Rangan Chatterjee
Yeah, I think I've already got a list there which will make a really good, good part two, just to finish off this part one, cold immersion. Again, I'm also fascinated by some of the research. I think the psychological benefits, of course, are profound when we do something uncomfortable and learn to control our response to that.
- [127:49]
Dr. Ben Bikman
Well, well said. You know, I like how you just said that. Well said.
- [127:53]
Dr. Rangan Chatterjee
And also, of course there can be these biochemical benefits as well 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 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, 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?
- [128:39]
Dr. Ben Bikman
Never.
- [128:40]
Dr. Rangan Chatterjee
Yeah, well, unless they live in the mountainous regions, of course. 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? And I'm not expecting you to necessarily have an answer 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.
- [129:37]
Dr. Ben Bikman
Yeah, I think this could be an instance of not. You know, earlier we had mentioned a similar conundrum with regards to high insulin and high ketones. I think that this could be another instance of us saying, let's not let an evolutionary view prevent us from taking advantage of an intervention. So 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 person. I'm always kind of on and I just have a hard time being calm and quiet in my mind and even just tapping my toes all the time. Not to mention just very poor sleep habits. And 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 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 can't quantify this, but I swear by this that it told my body, I'm awake now and it's time to start the clock. So that by the time the evening would roll around, I would be much more tired in a very good way. It was very satisfying feeling to be tucking the kids in, to be going into my room, tidy up the home a little bit and just starting to feel this sleep pressure get to a point that I knew I'm going to lay down and I'm going to fall asleep quite quickly. So for me it was this mental central effect, the metabolic effect, I didn't need to pay attention to as much. And then I haven't really. I'm already pretty healthy. I have a lot of other healthy habits. That's not to say it couldn't help someone in that regard, but that's actually not why I did it. Even though I first presented cold immersion from a metabolic perspective, and I would certainly defend that, for me, it was not born from a metabolic interest, it was more born from a nervous system anxiety, sleep perspective.
- [132:03]
Dr. Rangan Chatterjee
Yeah, so, so fascinating. Ben, I've thoroughly enjoyed this conversation with you. I love your attention to detail. I love the passion that you have for this topic. I know there's many topics we didn't get a chance to explore today, which we will do in the near future, I hope. But just to close off this one, if somebody has heard this conversation, Ben, and has realized that, you know what, I've not been taking my health as seriously as I could have done. They're pretty sure that they have issues with their metabolic health, they're pretty sure they have insulin resistance and they've been putting off doing something about it. I just wonder what would your final words of advice be to them?
- [132:56]
Dr. Ben Bikman
Thank you. I've really enjoyed this as well. I would maybe give two pieces of advice and they work together. 1. Think of your reason for wanting to improve your metabolic health. I have found that if it goes beyond just wanting to lose weight for the sake of losing weight as just an obvious one, then I think your motivation will be better, it'll be stronger. So have a reason for wanting to be healthy. And I would hope to some degree it's because of a sense of family or community that you have people you want to be with and be with for a long, healthy, enjoyable time. So have a reason for wanting to make these changes that goes beyond weight loss. And then number two, a more practical application would be change breakfast tomorrow. That it has become a meal of dessert in many, many places global at this point. This is not just an American phenomenon. Now change breakfast tomorrow. Either fast through it and have a warm, a hot cup of maybe coffee or tea even with a little dab of butter, which can help making the fasting a little easier or just control carbs, Prioritize protein and don't fear the fat that comes with that protein. So change breakfast tomorrow. It is the least impactful meal to change with regards to social oddities or social dynamics or obligations. It's the simplest meal to change and arguably it's going to be the most important because it sets you up to succeed through the day.
- [134:26]
Dr. Rangan Chatterjee
Yeah, love that, Ben. And I just want to acknowledge you here at the end for all the work you do in the public domain. You're a hardcore scientist, you run a lab at a university, you're a professor, but you still spend a lot of time going on podcasts, recording videos, writing books, trying to help people understand just how they can take control of the health. Of course, in the background I can see your first book, why we Get Sick. The second one I can't say. I think it's how not to get Sick. How not to get sick. I know. I believe you're working on a third book, which is super exciting.
- [135:01]
Dr. Ben Bikman
I am.
- [135:02]
Dr. Rangan Chatterjee
There's of course your website and also your YouTube channel. But for people who want to sort of get more info from you, where would you have them go?
- [135:11]
Dr. Ben Bikman
Yeah, I think simplest, I would just direct people to my website. Go to benbickman.com and Bickman is spelled B I K m a n. Benbickman.com and you can find everything I'm doing.
- [135:22]
Dr. Rangan Chatterjee
Yeah. Fantastic. Well, Ben, thank you so much for making time for coming on the show and I look forward to a part two in the very near future.
- [135:29]
Dr. Ben Bikman
Indeed. I agree. Thanks. This was wonderful.
- [135:35]
Podcast Host/Announcer
Really hope you enjoyed that conversation.
- [135:38]
Dr. Rangan Chatterjee
Do think about one thing that you.
- [135:40]
Podcast Host/Announcer
Can take away and apply into your own life.
- [135:44]
Dr. Rangan Chatterjee
And also have a think about one thing from this conversation that you can.
- [135:47]
Podcast Host/Announcer
Teach to somebody else. Remember, when you teach someone, it not only helps them, it also helps you learn and retain the information. Now, before you go. Just wanted to let you know about Friday 5. It's my free weekly email containing five simple ideas to improve your health and happiness. In that email I share exclusive insights that I do not share anywhere else, including health advice, how to manage your time better, interesting articles or videos that I've been consuming, and quotes that have caused me to stop and reflect. And I have to say, in a world of endless emails, it really is delightful that many of you tell me it is one of the only weekly emails that you actively look forward to receiving. So if that sounds like something you would like to receive each and every Friday, you can sign up for free@drchatterjee.com Friday 5 Now if you are new to my podcast, you may be interested to know that I have written five books that have been bestsellers all over the world covering all kinds of different topics. Happiness, food, stress, sleep, behavior change and movement, weight loss and so much more. So please do take a moment to check them out. They are all available as paperbacks, ebooks and as audiobooks which I am narrating. If you enjoyed today's episode, it is always appreciated if you can take a moment to share the podcast with your friends and family or leave a review on Apple Podcasts. Thank you so much much for listening. Have a wonderful week. And please note that if you want to listen to this show without any adverts at all, that option is now available for a small monthly fee on Apple and on Android. All you have to do is click the link in the episode notes in your podcast app and always remember, you are the architect of your own health, making lifestyle changes always worth it, because when you feel better, you live more.