Fat Cell Scientist: 99% People Lose Weight & Stop Disease Faster With This Insulin Trick

1. RCDr. Rangan Chatterjee0:00

   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?

2. BBDr Ben Bikman0:45

   Right. I am thrilled you're allowing me to start with answering that one question, because if we don't take a moment to define the villain of the story, then the rest of the story doesn't make as much sense. Insulin resistance is a two-part problem, and it's really important for people to appreciate the second of the two that I'll mention in order to understand the breadth of problems that stem, that grow from this diseased tree that we're calling insulin resistance. The first part of insulin resistance is what the name evokes, which is the idea that the hormone insulin isn't working as well as it used to, that some cells have become resistant to insulin's effects. Where insulin is coming and knocking on the door of the cell, some cells aren't responding as well as they used to. So that is what gives us the term insulin resistance in the first place. But the second part of this pathology, this two-part pathology, has to be articulated and appreciated in order to understand the diseases that come from insulin resistance. And that second part is that blood insulin levels are elevated. So that's a condition called hyperinsulinemia. These two things always come together in the body. Insulin isn't working perfectly at all the cells of the body, and blood insulin levels are elevated. And then the reason this problem can give birth to so many other issues, including the ones you mentioned and even more, is I believe it's simply a reflection of the importance of metabolism and metabolic health. There's so much of a description and a focus on metabolic health these days, and I applaud that. I rejoice in that. And yet I somewhat wince at the lack of clarity. Metabolic health is best defined as looking at the degree of insulin resistance, and insulin is the master metabolic hormone. It is the one hormone to rule all others. And, and if it's not working well, then metabolic processes in cells throughout the body are not going to work well. And then as metabolism is disrupted, health is disrupted. And then you have all those disorders you mentioned. Now all of a sudden the fat cells don't know what to do with the energy appropriately. Neurons of the brain are not getting adequately nourished because they can't obtain glucose. And then insulin has a lot of these unexpected effects, including affecting sex hormone production, thus giving rise to things like PCOS. So the relevance of insulin resistance, I think, is a reflection of the fact that metabolic health is a foundation to health in general, including chronic disease.

3. RCDr. Rangan Chatterjee3:25

   Yeah, it's interesting. These terms insulin resistance and metabolic health, certainly in health circles, are getting used more and more. I, like you, have been talking about this for many, many years now. I'm not sure if you're aware, in-- back in twenty fifteen, and I filmed this in twenty fourteen, I filmed the very first documentary globally to show that a condition called type 2 diabetes could be put into remission in just thirty days. And, you know, it's crazy to think that was ten years ago now. And it was deemed r- by some people controversial at the time, although it's not deemed controversial today. But I think one of the problems is, is that those terms, I think the lay public doesn't know what it means. You know, they know what cancer means. They know what a heart attack is. But insulin resistance, metabolic health, you know-

4. BBDr Ben Bikman4:21

   Yeah

5. RCDr. Rangan Chatterjee4:21

   ... those terms don't really land with them, I think, in the same way.

6. BBDr Ben Bikman4:26

   Oh, I, I fully agree. In fact, uh, please pardon what may sound like a bit of a plug. When I first wrote my book about insulin resistance, I had toyed around with the idea of giving it a title of something like Insulin Resistance: Why It Matters and Why You Should Care, but I knew no one would care because to most people... In, in fact, to most people, insulin isn't even a hormone. Most people hear the word insulin and think of it as a drug, as a therapy for diabetes. And so it's been, uh, difficult to help people appreciate that insulin is the master metabolic hormone and that when it's not working well, diseases will follow.

7. RCDr. Rangan Chatterjee5:09

   Yeah. Now, you are a big fan of the low-insulin lifestyle, as I am. Before we get into those sort of practical things that people can do to try and address this, are you able to give us an idea of the scale of the problem? I mean, I mentioned at the start all kinds of different conditions, basically to try and showcase to people that you're probably someone who wants to address this, unless you happen to be one of the very few people who are metabolically healthy. So it'd be quite, be quite good to get an understanding of how large is this problem, but then also what has actually caused it, because I suspect, you know, a lot of people out there have probably got some quite differing views on what the root cause of this problem is.

8. BBDr Ben Bikman5:58

   Hmm. Yeah.The s-- the scope of the problem is remarkable, and indeed, it's been a part of my motivation to continue to focus on this as a scientist for so many years. Uh, within the United States, I can, I can start there and, and then start to extrapolate a little bit because I think some of the data starts to get a little, uh, murky. Within the United States, the problem is sobering, where a report was published in two thousand and sixteen here, which did a, a national survey to try to understand the prevalence of the metabolic syndrome. And they found that eighty-eight percent of US adults had at least one part of this five-part constellation of, of problems that we call the metabolic syndrome, elevated waist circumference, uh, hyperglycemia, hypertension, and then I guess I could call the last two just dyslipidemia, uh, low HDL and elevated triglycerides. So that five-part problem is what constitutes the metabolic syndrome. Again, one, uh, at least one of those was found in eighty-eight percent of US adults. Quite sobering. Now, someone listening may be thinking, "Yeah, but Ben, you were asked about insulin resistance." What we call the metabolic syndrome used to be called the insulin resistance syndrome, and I-- it is a, a superior term because it's more precise. It, it doesn't quite have the ring to it like metabolic does, so it might not sound as good. But this suggests that eighty-eight percent of US adults have some problem arising from insulin resistance. That's quite sobering. Now, I know you have a very international audience, and some may say, "Well, it's just because the Americans are all so fat." Well, interestingly, and even somewhat paradoxically, while Americans are certainly quite fat and, and we're I think in the top ten, although not the fattest, but we're up there, we are not even in the top seventy countries when it comes to type 2 diabetes, one of the main manifestations of insulin resistance. Then if United States is barely in the top hundred in that regard, I think we're in the seventies, then clearly the rest of the world also has a problem. I don't think that mitigates the problem here in the United States metabolically, but it does suggest that this is a global problem. And when you, when you're able to look at type 2 diabetes, which is a more clearly defined clinical situation than insulin resistance, and, uh, we can revisit that later, insulin resistance just isn't measured, uh, or monitored appropriately. But if you just look at type 2 diabetes and use that as your surrogate of insulin resistance, then there are countries throughout, well, South Asia, South Asia, China, Southeast Asia, East Asia, um, the Middle East, uh, these are all countries that have far higher rates of type 2 diabetes than we do within the United States. So this is a global problem. As bad as it is here in the US, it is a-about as bad, if not worse, in many countries around the world, and even in ways you wouldn't expect. So, and, and that maybe brings me to the second part of what your question was, which is what causes it. I think to really appreciate the global scope and why is it that you can look at the United States, where we have such high rates of obesity and, and, you know, relatively normal or modest rates of type 2 diabetes, and then compare it to a country like Singapore, where I did my fellowship research many years ago, and one of my children was born there, and I love that place. Obesity rates are very modest, and yet type 2 diabetes rates are fantastically high, where Singapore is sometimes in the top ten of the most diabetic countries on the planet. There is something here that goes a little beyond diet now because these are very different diets in very different parts of the world. Although globally, the global diet is getting similar, and maybe I'll start with that point. For the sake of time, I, I, I will articulate two, two origins of insulin resistance. One is that I call-- One I call fast insulin resistance. This is where you can take humans and induce insulin resistance in hours, and as long as that stimulus persists, the insulin resistance will persist. And then once that stimulus goes away, the insulin resistance goes away. That one is chronically elevated insulin. So the more a person is eating a diet that is filled with refined sugars and starches, the more their glucose levels are spiking and the more the insulin levels are going to be elevated. And just to help people appreciate that, at a, at a now global level, the average individual wakes up, they've been fasting overnight, hopefully, their insulin has come down, and now the average individual spikes up their insulin with some sugary drink or some sugary bowl of cereal or some starchy, uh, baked item on a plate. And then they do something similar for their mid-morning snack, and then lunch, and then afternoon snack, and then supper, and then an evening snack. So the average individual is spending every waking moment in a state of elevated insulin, and too much insulin causes insulin resistance. This is something that's been shown to happen in as little as six days in very healthy college-aged students. You just give them-- start having them eat more refined sugars and starches. After six days, their fasted insulin levels are two and a half times higher, all while glucose at a fasted state stays normal, and that's one of the problems with just measuring glucose. But that is all to describe the fast insulin resistance. If you help insulin come down, then the body becomes much more insulin sensitive quite quickly. But that doesn't necessarily explain why in, say, the United States we seelower levels of insulin resistance than perhaps we see in Singapore. That's the slow insulin resistance where it's actually driven by the size of the fat cell. We have a mistaken view when it comes to body fat and insulin resistance or metabolic health in general. We tend to think that mass matters most. It doesn't. The size of the fat cell is what determines the metabolic consequences of that fat tissue. So if a person has more fat cells but they're smaller, they will actually be metabolically okay. Their blood markers will be fine, their cardiovascular markers will look all right. They're just quite chubby. This is what you tend to see in Caucasians and African ethnicities. They have this genetic ability to make more fat cells, and so if their body has a pressure to store more fat, which it is a whole other topic, then they will reproduce fat cells. And so they have more fat cells, but they're smaller, and small fat cells are insulin sensitive and anti-inflammatory, and both of those are important for maintaining overall cardiometabolic health. In contrast, on the other end of the spectrum, we have East Asians and South Asians and Hispanic, Hispanics here in the Western Hemisphere. Those are ethnicities that have a lower ability, a lower propensity to stimulate new fat cells. So as there is a pressure on that body to store more fat, the fat is left being stored in ever-growing fat cells. Uh, that's a process called hypertrophy. And so as the fat cells are undergoing ever more hypertrophy, they become very insulin resistant to try to stop their growth, almost like a, a naughty child who's filling a water balloon. The water balloon's about to burst if you put any more water in there. And so the fat cell senses it's reaching a point of maximum dimension, and it will become insulin resistant to stop its growth. Now, it won't shrink, but it'll stop. At the same time, the second point here is that as the fat cells are getting so big, they are pushing each other further and further away from capillaries and the life-giving blood that is flowing through them. And in an effort to try to correct that lack of blood flow and that lack of oxygen, the fat cells will begin secreting a host of pro-inflammatory hormones called cytokines, some of which will tell those capillaries to start growing off a new capillary line to feed those starving fat cells. But the overall process, the overall consequence of this will be very pro-inflammatory. So to wrap all of that up, the problem is very prevalent globally. We've already discussed a little bit why it's so relevant with leading to chronic disease. But we also, when we look at the fast insulin resistance, too much insulin causes insulin resistance, and that can be corrected by just bringing the insulin down by avoiding refined sugars and starches. On the other hand, that doesn't necessarily explain the ethnic differences that we see. Why is it that a moderately chubby South Asian now has all of the consequences of insulin resistance, like fatty liver disease, hypertension, and erectile dysfunction, whereas his Northern European Caucasian roommate, who's just as chubby as he is, is doing perfectly fine? That's not because of the fast insulin resistance, but rather because of the effect of the size of the fat cells, where he has fewer but fatter fat cells, whereas his colleague, roommate, friend has more fat cells, but they're smaller.

9. RCDr. Rangan Chatterjee15:30

   Yeah, it, it's so interesting. I really appreciate the nuance there. If I can just try and summarize where we're at so far, we're talking about the fact that the world basically [chuckles] has poor metabolic health, and you mentioned a very alarming statistic in America, eighty-eight percent of people perhaps. I've seen some studies showing perhaps a little bit more, but a lot of people have problems with their metabolism, which very simply speaking, is the way we utilize and process energy in our bodies. And so of course, if you think about it on a macro level, this is a huge problem. You know? One, one of the sort of core things we need to do as a human being who wants to function in the world is to process and metabolize energy efficiently. If we cannot do that, yes, we're gonna have low energy and fatigue in the short term, but also this increased risk of many other kinds of conditions that we've already mentioned. Okay, so that's a starting point. But you then were sort of explaining very beautifully that America, whilst it has high rates of metabolic dysfunction and high rates of obesity and people carrying excess fat on their bodies, you're saying that proportionately, type 2 diabetes is not as high as you would imagine if the only thing driving the type 2 diabetes was metabolic dysfunction and obesity. You're saying that there's a subtlety, there are genetic predispositions based around our ethnicity, which means that we tend to store fat in different places. So me and you are a prime example here, right? So my parents came to the UK from India in the 1960s and 1970s, so I have a South Asian background, and therefore, from what you're saying, if I consume an excess of calories, I'm likely to store fat in a different way to how you are. Is that a reasonably accurate, uh, summary of where we are so far?

10. BBDr Ben Bikman17:49

    Yeah. Yeah. In fact, and then, and then just to finish that thought or, or to tag onto that thought, my own ancestry primarily came from England, ironically. Where yours went to, mine came from, and so w- you and I do represent two very beautiful examples of the ends of the spectrum. So if you and I both gained-10, 10 pounds of pure fat, ge- genetics would suggest that I would simply just be that much chubbier and, and perhaps not as flattering in my Speedo. You would have that same physical consequence, but because your fat cells are now much bigger than mine, you are gonna have consequences of insulin resistance. And just to put a fine point on that, there was a study done that, that looked at fat, weight-matched men, Caucasian and South Asian, and they performed an adipose biopsy. We've done this in my own lab t- as well, where they removed a small portion of abdominal fat. And then-- And remember, these men looked the same, so if you s- had, had the two of us standing next to each other, let's just say we're about the same height, same overall body weight, they matched these individuals, and yet the fat cells from the South Asian men were on average, uh, with diameter over three times the diameter. And that's just the diameter. When you look at the volume, that is multiples, maybe ten times larger of a fat cell, even though the men were the same fatness and body size overall. They were con- they controlled for this. So yes, fat cell size will be substantially different for any given fat mass across, say, Caucasians and South Asians, just as an easy example, uh, on average. Now, one other point of nuance where, where you described what would have created that fat mass in the first place. Yes, calories matter, uh, definitely. That energy must be accounted for. However, there is a danger in invoking the principles of thermodynamics in humans because we are not steam engines. The origins of thermodynamics, which is fascinating, um, i- it has created an overly simplistic view, I think, that gets us into a bit of trouble because in this same study that looked at fat cell size, it-- between Caucasians and South Asians, the fasting insulin in the South Asians was about two to three times higher, actually mimicking somewhat the diameter of the fat cell. It was significantly higher, a multiple higher at a fasted state. And that is critical because as you mentioned, and I've mentioned now, I think, insulin is what helps the cells of the body know what to do with energy, and the fat cell is the perfect example. As much as calories matter, the fat cell must be told what to do with those calories, and insulin is the signal that tells the fat cell to grow. Now, again, I'm not saying calories don't matter, but when we look at what is driving that fat expansion, what is driving the body to store more fat, calories is one part of it, but we should also consider, well, what are those calories doing to the insulin, uh, level? And then what is the insulin then telling the fat cell to do? Because if you wipe out the insulin like it is impossible, utterly, totally impossible to hold on to, let alone gain any fat mass. So, so yes, calories matter, uh, but so too does insulin in telling the body, especially the fat cells, what to do with those calories.

11. RCDr. Rangan Chatterjee21:22

    Yeah. Let's just stick on this example using you and me, 'cause I think it's, uh, given our respective ethnicities, it's-- I think it's a really interesting way to try and tackle this topic. So I appreciate the nuance around calories and of course, insulin is... You know, it's an anabolic hormone, isn't it? It tells the body to store things as opposed to break down things. And we are living in societies now where many of us, because of our lifestyle, and it's not just diet, but let's say because of the way we're eating food, amongst many other things, we're having these chronically elevated levels of insulin. So those chronically elevated levels of insulin are encouraging us all to store fat on our bodies. But the difference between you and me, uh, Ben, if we were the same height, and we were the same weight, and we had similar levels of high insulin-

12. BBDr Ben Bikman22:26

    Mm-hmm

13. RCDr. Rangan Chatterjee22:27

    ... 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.

14. BBDr Ben Bikman22:36

    Mm-hmm.

15. RCDr. Rangan Chatterjee22:36

    So we may both be regarded as obese by certain metrics, but you may actually be metabolically healthy with your high BMI, and so not have an increased risk of cancer, Alzheimer's, type 2 diabetes, heart attack, infertility, et cetera. You, you could basically be fat but metabolically well, and I could be the opposite. We-- I could have the same BMI as you, but because of my ethnicity, I'm not gonna make new fat cells. I'm just gonna use my existing fat cells and stuff them full of fat. They're gonna expand. They're gonna start leaking out inflammatory markers all around the body. Whereas you are gonna make new fat cells, and they're gonna all be small and tight, so you're gonna look fat perhaps, but-

16. BBDr Ben Bikman23:33

    Mm-hmm

17. RCDr. Rangan Chatterjee23:35

    ... the markers for long-term health are gonna be sub- significantly different with you. Is that accurate, the way I've, I sort of articulated it?

18. BBDr Ben Bikman23:45

    Yes, yes, perfectly. If I would just add one final comment, that this whole concept, when it was first posited in some, in, in maybe its clearest form, was described as the personal fat threshold.

19. RCDr. Rangan Chatterjee23:56

    Hmm.

20. BBDr Ben Bikman23:57

    So how much fat can a certain body hold before it starts to suffer consequences of that fat? And in broad terms, we would say Caucasians, I have the ability, my fat threshold is much higher. I can store much more fat before it has a negative consequence. And we would say your, in broad terms, personal fat threshold is lower. So you don't have as much-... storage capacity. So once you reach that threshold, you start to experience the consequences of it. And again, it's not fat mass, but as you've just reiterated now, it's the size of the fat cell that matters. And there are different genes that have variants. For example, just to really drill down, w- it's very, very likely that the average South Asian, for example, has a variant that is l- uh, uh, of a gene called PPAR gamma, and where P- and PPAR gamma is the main gene regulator that determines the birth of new fat cells. And this has been s- this has been shown to happen across ethnicities, where the PPAR gamma is a less active variant, whereas in, say, Caucasians, PPAR gamma's quite active. And, and people can actually see this at a, at a broad level. If anyone's ever curious to go and, and wants to have sort of a, a, a morbid evening of entertainment, you can look for TV shows about individuals who have gained just superhuman levels of obesity, you know, 500, 600 pounds, and they are almost always going to be Caucasian or African ethnicities. It's extraordinarily ... You would never find an East Asian. Uh, it would be extremely unlikely to find a South Asian, uh, pr- pretty much impossible. These are ethnicities that simply cannot get that fat because they don't have the ability to endlessly make new fat cells.

21. RCDr. Rangan Chatterjee25:48

    Yeah, it's kind of interesting. If I reflect on my childhood and a lot of my parents' friends of a similar background, it, it would be quite common in the sort of Bengali Indian community for the guys as they get older to have thin arms, you know, thin legs, but there'd be a belly. And as they get older, you'd see that belly protruding out more and more, um, which is kind of interesting, which kind of plays in here to what you're saying.

22. BBDr Ben Bikman26:17

    Mm-hmm.

23. RCDr. Rangan Chatterjee26:18

    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?

24. BBDr Ben Bikman26:42

    Right. Right. Well, this, this theory can only go so far as, as so many theories when it comes to evolution can. Uh, but one theory would be this idea of where you're located on the planet, how much vitamin D you need to make, and the degree to wh- or how much sun you need to make vitamin D, and the degree to which that is a temperature that requires more insulation. So to, to put all that in more clear terms perhaps, let's say with my very fair skin, my ancestors could thrive in relatively lower light conditions, which would put them closer to the poles.

25. RCDr. Rangan Chatterjee27:20

    Hmm.

26. BBDr Ben Bikman27:20

    Let's say closer to the north, um, in this case. And so a little light a day, a little sunlight will penetrate my very fair skin very easily, make all the vitamin D I need, but it's also going to be quite cold. And so one adaptive response would be the ability to make fat cells, especially subcutaneous fat cells, the fat cells that act as a warm jacket going a- all around under the skin of my body, so acting therefore as a good insulator. But let's say your ancestors, with your darker skin complexion-

27. RCDr. Rangan Chatterjee27:51

    Hmm

28. BBDr Ben Bikman27:51

    ... you need a little ... You're pr- you're not only protected from the sun, you're gonna get sunburned much less readily than I am, but you also need a little more direct light to make sufficient vitamin D.

29. RCDr. Rangan Chatterjee28:02

    Hmm.

30. BBDr Ben Bikman28:03

    That's als- that's going to put you closer to the equator, which is going to mean you don't need a lot of insulation. Fat isn't as protective. And you might not also have as much scarcity as my ancestors have, where I wanna have the ability to store a lot of fat in the event that-

Episode duration: 2:11:24