Hey everyone. Welcome to the Peter Atia drive. I'm your host Peter Atia. The drive is a result of my Hunger for optimizing Performance Health longevity critical thinking along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top-performing individuals in the world. And this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality more fulfilling life. If you enjoyed this podcast, you can find more information on today's episode and other topics at Peter TMD.com.
Everybody welcome to this week's episode of the drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why instead we've chosen to rely entirely on listener support. If you're listening to this you probably already know but the two
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About for free and have them pass savings onto you again the podcast will remain free to all but my hope is that many of you will find enough value in one the podcast itself and to the additional content exclusive for members to support us at a level that makes sense for you want to thank you for taking a moment to listen to this. If you learn from and find Value in the content, I produce please consider supporting us directly by signing up for a monthly subscription. I guess this week is dr. Jason Fung. Jason is a nephrologist in Toronto Canada, many of you listening to this podcast probably already are at least familiar with him just before another reason through social media or other channels. He's quite a vocal critic of the conventional approach to treating type 2 diabetes and he also has in my experience at least one of the most significant clinical practices that utilizes fasting as a treatment for metabolic disease.
Jason relatively informally for quite a while but I've gotten to know him better in the past year and was really looking forward to doing this interview because I certainly get asked a lot of questions that I think Jason would have great insight into is the author of several books including the Obesity code. The diabetes code the complete guide to fasting and the longevity solution is the co-founder of the Intensive dietary Management program Jason graduate from the University of Toronto and completed his residency at UCLA in this episode. We talk about a lot. We actually kick it off with a discussion. I didn't plan to get into but I thought it was really interesting and I hope you do as well about evidence-based medicine and you know the difference between the taking two scientific disciplines one of medicine biology the other of physics and comparing and contrasting some of the differences. I sort of make an argument around theoretical versus experimentalists things like that and talk a little bit about Nephrology. What took Jason into that field and why is being a nephrologist a doctor who specializes in kidney disease. Why does that?
Him a quite unique insight into kind of the early indications of metabolic disease and then we get into the meat of this thing, which honestly I think this is one of the most interesting discussions I've ever had on insulin resistance and you listen to this podcast. You've heard me talk about that a lot and I think Jason's take on this quite frankly is probably the smartest thing I've heard now that doesn't mean that I necessarily agree with everything and that doesn't mean that there aren't holes in these arguments but his explanation for why a concept of insulin resistance, which is very difficult to explain when you try to parse it out into tissue specific effects of insulin. He has a much better explanation for this that clinically makes more sense and ultimately results in a much more logical treatment plan. So once we go through this discussion of what people call insulin resistance and Come Away with this idea of hyperinsulinemia for which by the way has a great example using a suitcase that I'd never heard before but I took the liberty of bolting on to it as much as possible.
So by the end of this you might be sick of hearing about suitcases. We talked a little bit about nafld e and then we close the discussion. So if there's sort of a final part of this it's getting into the clinical stuff the use of dietary restriction including ketogenic diets carbohydrate restriction, but most of what we talked about pertains to fasting and I think that that's where a lot of people are going to be kind of interested. Jason has a very different approach to fasting than I do in my practice and I think that probably stems from the fact that I'm not treating patients who are nearly as sick as Chase and so in that sense, he has to be a little bit more extreme out of the gate and to listen to some of the the clinical wisdom that he brings to this is even for me quite informative. So I hope you enjoy this discussion with Jason half as much as I did. There's so many things I want to talk about with you and I would say that you are among the three people top three certainly that on social people are always saying when are you going to interview Jason when you going to interview Jason and of course
Plan to do this in December in person and that's when I had my whole Dental Calamity that required like tooth extraction after secondary tooth extraction. Also, I never made it up. So anyway, I'm glad we could do this and I appreciate everyone's patience with this but I guess the broader point is I think people are so interested in speaking because of all the work you've done around fasting insulin resistance and just overall. I mean, you're a clinician on the front lines. I mean, you know, it's one thing to sort of pontificate on Twitter. It's quite another thing when you actually show up in clinic and see hundreds of patients as you do thanks. I mean, I think that's one of the things that I think distinguishes me from some of the other people that are out there is that stuff's got to work. Otherwise, it just ain't worth it. Right like you can talk all you want about this and that but if it doesn't change management, then it doesn't interest me particularly because that's where I come from and I think this is where a lot of people get sort of they see these academics and they say, okay.
They know everything about this. It's like well, they might know everything but if it doesn't work on the front lines, it's not worth anything. I think this is an attitude. I see like in physics, which is I know you you really look up to Richard feinman as do I but I actually love the whole story of you know, Einstein and Niels Bohr and all that because physics to me is sort of like I love that because the way they do science is so much better than we do in medicine that is to say for in this specific instance. For example, if you have all these theories, they're great. But if they don't agree with experimental evidence, it ain't worth anything, right and they say this in physics, but they don't say this in medicine where it's like, okay, you think that yo eating lots of carbs is really good for you, right? You have this hypothesis that eating less fat and tons and tons of refined carbs is good for you and that's a great Theory at all makes sense and the same thing with calories.
Like it sounds like if you just cut calories it makes sense. But if your theory doesn't work, then it's not a good theory. And this is what they say in physics which they don't say in medicine and in medicine at always like boggles my mind how these bad theories go round and round and round because they make sense, but nobody's actually put them to the test or nobody's point out these things and it's the same with insulin resistance. I think actually to me the most important topic is sort of insulin resistance because again, that's what I deal with as a nephrologist. I see a lot of type 2 diabetes that to me is completely sort of misunderstood and the way we think about insulin resistance is sort of totally wrong and that's why we have the sort of mess that we have. I think well, we're going to get to that for certain. I definitely like to build on what you've said. Yeah. There's a beautiful demonstration of what you described. It's a video from either Caltech or Cornell I can't recall so it was either right before he had left corner.
After he had arrived at Caltech we're finding is that a Blackboard and he is explaining the scientific method in about as elegant way as you can which is to basically say which you did which is this is the scientific method you make a guess you design an experiment to test the consequences of that guess you do the experiment and if the output of that experiment aligns with your guess the hypothesis turns out to be likely correct or more likely to be correct. And if it doesn't you go back to the drawing board and the Simplicity with which one of the most brilliant physicists of the 20th century explains that is not lost on anyone who watches it and I would agree with you completely I've gotten into trouble by saying this before but I guess I guess on your podcast you can sort of say what you want. But I'm generally suspect of people who have very very strong points of view on things in biology or medicine who no longer interact with patients doesn't mean that they're wrong but I'm generally suspect because of that because the other thing is biology is harder than physics the reality. It's just a lot Messier and sometimes people ask me, you know, do you
Always see patients and the answer is yes, I think so and I hope so because they are kind of a humbling tool every time. I think I've really got it figured out. I'll always meet a patient who proves me wrong and they're obviously right and I'm wrong and I think the other part about physics which I love is that the way they think about it is that there's you know, a theory like Newton has a theory for example, and it explains a lot as a great Theory and everything but then there's these anomalies and the anomalies are what drives sort of science for because you have to come up with a better theory that explains the anomalies and if you come up with a better Theory they make these wild predictions and if these wild predictions are true, you know, this new Theory can sort of supplant it so the way Niels Bohr and the quanta supplanted sort of Einstein even though he was brilliant. So the point is that that doesn't happen in medicine in medicine. We have this super laborious process of evidence-based medicine where instead of saying hey, here's a theory that
Makes more sense because explains everything what they do is they say every single point that go where's the evidence? Where's the evidence? Where's the evidence? So that's why nothing ever moves forward like I do the same thing in the frolla G that I did 20 years ago when I was doing my training it's like what was the last Advance we had right? It's like so from so long a word like most of the advances in medicine for example, come from like aspirin. It counts for like 50% of the progress. We've made it's sort of ridiculous. Whereas physics sort of moves, you know at light speed because they don't demand the sort of evidence base and I always say that, you know, evidence-based medicine is good. If you know how to apply it right because the whole point of evidence-based medicine is that it's not a search for truth. It's a search for consensus and it may or may not be true. But if you have a crazy Theory and then you send it out to five people and they say well it's crazy. It gets killed. So if you have like a theory
Hey, the earth goes around the Sun not the Sun goes around the earth. You send it to a consensus of peers. They say no no, no clearly the you know, the sun revolves around the earth that would never have made it through. So the evidence-based medicine is not everything like you have to understand where to apply it. And this is where I think we've gotten into so much trouble is that every sort of advanced moves glacially because we sort of demand that things have to have evidence. So something like fasting for example, which I always get into trouble a lot to write again two tons of trouble for calories. Everybody tax me for all kinds of stuff but fasting five years ago was the dumbest thing you could do right now. I'm like why like, it doesn't make any sense that it should be so bad, right? So I thought about it and I went through it and then I just brought it immediately to patients right just treated hundreds and hundreds and hundreds of patients and the results like amazing and of course if you don't eat you're going to lose weight.
If you don't eat your diabetes can get better, right so it worked and that was the point like you got to get to that point where it's like and then everybody says to me. Oh, where's the evidence? I'm like, why do I need evidence? Like people are getting better. Right? I'm not a researcher, right? You can come up with the research, but just try it on people look at it. But all these people are saying oh, there's no evidence. There's no evidence clearly as bad and that's where everything just sort of bogs down. You get all these people who sort of demand that every sort of little step has to be based on consensus at the consensus moves. So slowly that you can't move. You can't move like Einstein movie can't you can't make those sort of intuitive leaps forward that always bothers me a lot. Well, it's sort of a problem it is there is a distinction right in physics. I think broadly speaking and again physicists will sort of bristle at the Simplicity with which I'm saying this but you can generally divide the field into the experimentalists in the theorists and that's what I think.
Allows the step function changes and understanding so Einsteins advances were theoretical so the experimental evidence to support these things came after but yes many times the big steps forward come on the basis of theoretical propositions and we don't really have that in medicine and biology. We don't have experimentalists and theorists. I've thought a lot about this actually and I didn't intend to go down that rabbit hole, but there's a whole separate podcast, by the way on this topic of how could you change biological research to take some of the advantages that we see in the physical sciences where you can create a symbiosis between the theorists and experimentalists. The last thing I'll say on this point. By the way that I agree with you is the real challenge of exclusively relying on evidence based medicine is that framework is very good for certain problems. It's actually quite good for problems that are rather acute for which the interventions to address.
Are rather simple and for which you will get an answer quickly. So in many ways the pillar of evidence-based medicine is infectious disease, if you think about how much we have learned through evidence-based medicine with respect to the treatment of HIV and frankly most infections. It's remarkable. I mean, we've really got that dialed in but again, if you take a step back and look at those criteria, well infections are quite acute typically very easy and binary to measure progression. The interventions are simple take this medication don't take this medication and that's much more complicated than well. I want you to exercise a certain way for this period of time where I want you to eat a certain diet for a certain period of time and then the resolution can be to whatever metric it is, whether it be T-cell count or amelioration of the clinical infection that occurs really quickly. So you're right. I mean II think evidence-informed medicine is probably a better way to think about it. But yeah someone like you is, you know, you're really
Neat Forefront of using your best ethical judgment to say look, I'm going to bring something to a patient population. The other thing I want to add by the way while I'm on my soapbox that you help me stand up onto is people are very quick to say well you don't have the evidence to support fasting for a patient with type 2 diabetes and you can say okay, that's true. So there is a risk that if this patient with type 2 diabetes goes on a fasting protocol something bad could happen. But what people in medicine I find are very I wouldn't even say quick to forget. I don't even think it registers is what's the risk of not doing something the risk of doing something is usually more in our Forefront. It's that risk of not doing something that people often forget and if the risk of not doing something is stay the course slowly slowly increase the amount of insulin this patient requires slowly slowly watch the micro and macro scopic vascular disease progressed. Well that risks actually at that's a pretty bad risk. Well, that's absolutely true and it's like
This is the point that I always made the patient's it's like if you keep on doing what it is that most doctors do including myself, right? I used to just give people tons and tons of insulin. I know what is going to happen and everybody acknowledges that if you'll just get worse over time and it was just sort of accepted as like there's the risk of not doing anything right, but if you suddenly change, you know, bring it in French in like fasting or low-carbohydrate diets ketogenic diets or whatever. There's a risk of doing it sure. We don't know what the risks are but, you know the risk of not doing something and that's the virtual certainty that you're going to in 10 years go on dialysis or something like that, right? Yes, that's not an insignificant risk. It's actually a huge risk compared to doing fasting which has been done for thousands of years and always say like look like the problem with evidence-based medicine and consensus and stuff. Look at look at what happened with the low-carb guideline. So as you know a couple days ago the American Diabetes Association came out with sort of new guidelines and they said hey,
Low, carbohydrates pretty reasonable it has the most evidence behind it's like five years ago. They're persecuting dietitians for giving low carb advice. Right? It's like, you know are the human body hasn't changed in the five years that it took for you to realize that right and that's where you're doing patients a real disservice by having these sort of expert opinions guidelines right where people can't decide for themselves like as a dietitian. You can't decide for yourself that you want to be low car because five years ago, they would have run you out and persecuted you right taking away your license and today like as of sort of two days ago. You're actually falling completely within American Diabetes Association guidelines, right? So it's like this is a big problem the flip side. I guess that's progress and we'll take it. Right and I've said this before it's sort of one of my little tongue-in-cheek comments, but you know, I'll fax have a half-life and some of those Half Lives can be quite short, but it is interesting to see this because it's been about
Ten years that I've been paying attention to this and these things typically do occur on five year Cycles go through the Ada the AHA and then in the United States, obviously the USDA. Also, I guess in fact - it's hard to believe we're coming up to 2020 this time next year. We'll be dealing with a new set of dietary guidelines, which I don't want to think about. So let's change gears for a moment. You're a nephrologist. So for people listening and that means you specialized after doing your training in Internal Medicine you then sub-specialized to double down on one particular organ a beautiful organ called the kidney which give us, you know, a little bit of a sense of like, what is it about the kidney that is so special because it is pretty special organ, you know, Internal Medicine everybody sort of divides themselves and types, right? So in medical school, it's interesting because you have the jocks who go into Orthopedics, right? And then you have the really sort of touchy-feely people and they go into family medicine and Pediatrics and Internal Medicine generally attracts a lot of people.
Sort of like to think about things and then within Internal Medicine, you have the sort of subdivision into the different types and generally went at least where I was going to school at the University of Toronto. The nephrologists were always the ones who like to think about things because that's all we could do and we can do it can do a lot about it. Like, you know, you stick people on dialysis and so on but they like to think about problems like Puzzles, like electrolyte problems and stuff. So you have this low sodium and low potassium's and what's happening in the kidneys because the kidneys do a lot in terms of homeostasis. They keep track of you know, they keep the sodium and check and you keep the proper amount of water and salt and potassium and calcium in the body. So it's fairly complex, but it's a specialty where people like to think as opposed to like GI which was towards these sort of action oriented people who like the scope and you know, snare things out and stuff. So that was really what attracted me to
Really was that that's sort of my my personality as I like to think about stuff. I like to work out puzzles. I'm addicted to Sudoku. It's just something I love to do and it's just the way I am. So that's sort of why I chose Nephrology and I wound up doing it that at UCLA. I do enjoy it and when I say there's not a lot we can do what I mean. Is that up to a certain point kidney disease you can treat them but there's really like to treatments right? There's prednisone then then dialysis. And the last time we had a drug that actually slow down progression of kidney disease was like the ACE inhibitors in the 80s, right? It's been a long time since things changed and just now we have the sglt2 is for diabetic kidney disease before that. It's like nothing so there wasn't a lot to do but at there's a lot to think about so that's sort of what I liked about it and the kidney I mean every organ is unique in its own way, but one of the things that I recall being sort of Blown Away by in medical
Was how smart the kidney was you don't think of it as a particularly intelligent organ you think of it as well? It's just a filter but there is a very clever design and evolution which said rather than the kidney learning. What is bad and figuring out a way to always get rid of things that are bad it was because it was the opposite it was learn. What is good and when you throw everything out during the first pass of filtration just learn to pull back the good because the probability that the good things are going to change is low the probability that you'll see new bad things is high and so I remember the nephrologist sort of standing there saying look it would be tempting to think that the kidney would operate like it's going into your sock drawer to pull out just the right sock but it doesn't it pulls out all of the socks and puts back the right ones and that allows sort of stuck with me one is a pretty interesting statement of just how important it is to have that system working and the second thing is how small the organ is and
What a high fraction of are circulating blood volume passes through it. And as you build on that which gets to some of the stuff we're going to talk about today why the kidney is such an early warning indicator of disease either through high blood pressure or high glucose. I mean is it safe to say that some would argue that the eyes are generally the first place you can see evidence of that disease of either high blood pressure high glucose, but the kidneys would probably come in pretty clothes as well. Wouldn't they? Oh, yeah. Absolutely. So the thing about the kidney is that they get like 20 percent of the entire circulation of the body. So it's a huge amount of blood that goes through and then the amount that comes out through the glomerulus, which is the sort of functional unit of the kidney is few huge. So basically they take everything out and then sort of put it back in. So that's why they can fine tune it so well, but a huge amount of fluid that goes through the kidney sort of all the time even though a trickle comes out as urine like it's filtering.
Ten times more than that so you might have a liter of urine a day, but you're filtering way more than that every single minute truthfully. So it's an incredible system and the reason that eyes and the kidneys are such early warning indicators is that the eyes is the best because you can actually directly visualize it's the only place you can directly visualize the blood vessel, but the glomerulus which is, you know, you have about a million of these glomeruli in the in the body, but they're basically a big bag of blood vessels. So if you're going to have two Z's is of the blood vessel, which turns out to be where are these metabolic diseases impact each other so the heart disease and kidney disease that comes later on but there's so many blood vessels in the kidney that it gives you this sort of early warning. So the first thing you generally see in terms of diabetes or high blood pressure you start to see this protein that appears in the urine so you can measure it something called the album and creatinine ratio and you
Actually see it. So when you start to get increased urinary albumin excretion what you know is that there is damage to the vascular system just because the vascular trees like so so big there and you can directly measure it. So if you were to go to your liver, for example, there's nothing you can measure right. So it's got a big vascular. So the lungs haven't been faster system, but you can't measure anything. Whereas the urine you can actually directly measure it and the eyes you can directly see it. So that's why they come out so early so increased urine album excretion actually a very very strong correlation to heart disease not because having a bit of urine and so bad but it tells you that there's something bad going on in the blood vessels of the kidney which tells you that something bad is going on in the blood vessels of the body. So that's why looking directly into the eyes is useful and measuring the urine is very useful. Yeah, and because my skills for looking into patients eyes are not good enough that I can reliably do that. I have in the past three years really started to pay much.
Retention to Staten see creatinine along with micro albumin for exactly this reason because it's sort of occurred to me in a momentary Insight that if my interest is in longevity, which means trying to figure out a way to get people to outlive what their expected time course is one of the most important organs that gets neglected is the kidney and if you are in your 40s, but you already have a glomerular filtration rate at 80% of what would be predicted. You have to fast forward a little bit and say well, what's that going to look like when you're 80 the net implication to me has been a much greater focus on blood pressure even sort of stage one. So slightly elevated blood pressure that I think many Physicians until recently probably just weren't thinking of as a significant enough problem. But once you do start looking at that micro abdomen and that's just at and see as a non nephrologist. We get a little bit of a window of insight into your world and there are a lot of people
Walking around I mean a staggering amount of people walking around who on the surface just based on their creatinine look pretty normal but a slightly deeper look says No, actually they're not normal. They are they are compromised and it won't be clinically relevant for 30 or 40 years, but that's going to be relevant. The thing is that there are no symptoms. So I see people all the time with diseases like IJ nephritis, which is the most common sort of primary kidney disease in the world and they will not know it and they will have lost sort of like 95% their kidney function by the time I see them just because they never knew they had a problem because they never checked it. It's very silent in that way. You just don't know you have a problem unless you start looking for these things and that's why it's important to sort of keep an eye on the urine is so easy to write it's not invasive anybody can do it.
Well, let's talk about this thing called insulin resistance because there's two broad broad topics. I want to explore with you today and I can see no better way to approach them. Then in this order. Let's start with the problem statement and then let's start to talk about the treatment. So I will confess at the outset Jason that as it's been nine or ten years that I've thought about this problem. I still have a hard time explaining to somebody certainly if I only have the duration of an elevator ride what insulin resistance is because I get tempted to get into well, it means this thing in this type of tissue but this thing in this type of tissue and blah blah, so let's not hold you to the standard of you only got an elevator ride to explain it. But how would you explain it both to maybe a lay person but then even at the level of nuance that we could sort of have a rigorous discussion about it, this is really what I think is the sort of most important problem in medicine, which is the metabolic syndrome.
And insulin resistance and the whole way that we sort of think about it. I think is completely wrong those kind of step back and say let's start with what we think is insulin resistance and taking this physics approach what's wrong with it? What parts of It Don't Fit the sort of experimental evidence if you will, so when we talk about insulin resistance and sort of I'll just step back a bit and say, okay. What do we think about insulin resistance the way I was taught about insulin resistance, which I'll tell you I think it's completely wrong and probably you were taught the same thing. Right? So the way we think about insulin resistance as we think about it only in terms of the glucose, right? So insulin is a hormone and when insulin goes up it allows glucose from the blood to go into the cells, we know that we know that glute for receptors go it goes into the cell membrane glucose and and now the cell can use it. So the reason we call it insulin resistance is because we know that there are
Levels of insulin as opposed to type one where there are low levels of instant there's normal levels of insulin, but the glucose is not going into the cell for some reason and when you measure the blood glucose for example is very high and there's insulin around. So if insulin is round why can't the glucose go into the cell and this is why we say hey if there's insulin then the cell must be resistant to the insulin. This is insulin resistance. This is the sort of lock and key Paradigm that we talked about. So insulin is a hormone it acts on the insulin receptor, which is on the cell surface and the insulin receptor is like a gate so there's a door there's a lock insulin is like the key so it opens the door and therefore the glucose can go from the blood into the cell the cell has energy to use so we can measure insulin we can also look at insulin receptors you can sequence and and you can tell there's actually nothing wrong with them. So insulin receptors are completely normal insulin is
The normal so what you say is that well, there must be something that's gumming up the system. So like a piece of gum that sort of stuck in that lock. It's gumming up the things you have a normal key. You have a normal lock, but when you put the key in the lock, it doesn't really work and then therefore the glucose can't get into the cell and the cell is now facing a internal starvation and the internal starvation is why we give insulin to move the glucose into the cell and that's our current thinking or at least what I was taught and what most people still think about insulin resistance, but it's almost completely Incorrect and there's no possible way can be correct because there's a central Paradox of insulin resistance, which is that insulin has actually many many different functions only one of which is letting glucose into the cell. So for example, we know in the liver that insulin is responsible for de novo lipogenesis that
As if you have a lot of carbohydrates glucose it will build it into glycogen and that is working fine. If there's too much glucose after the glycogen is full it's going to turn it into triglycerides are fat and that is working fine. So denovo lipogenesis is working fine. Let's take a state of type 2 diabetes, which is we acknowledged as a high insulin resistance. How can it be that you have a liver cell which can't let in the glucose. So it's resistant to the insulin yet. The other effect of insulin, which is de novo. Lipogenesis is not only working fine. It's actually going over time, right you can measure de novo lipogenesis and type 2 diabetes. It's super super high and what about the mitogenic effects of insulin. So insulin as a growth factor, you can measure it for example with large for gestational age babies. And you say that a woman is insulin resistance. Yeah.
Insulin is actually doing what it's supposed to do is actually stimulating a lot of growth. So there again insulin is super sensitive or say testosterone. We know insulin has effect on testosterone and PCOS and there is working again not just normally like super high. So in the liver you have this sort of central Paradox where you say in the same tissue to the same levels of insulin, you have both resistance and super sensitivity. Like that's not really possible. It's the same cell same thing, but they people call it selective insulin resistance. So that's sort of the central Paradox of insulin resistance and it doesn't really make any sense that this can be the way and Jason I would just add an even simpler observation to that which I've always struggled with which is a very common phenotype of insulin resistance is adiposity obesity remaining obesity, which of course
The accumulation of fat in a fat cells. So a fat cell is getting bigger well for a fat cell to get larger, it needs to incorporate triglyceride to incorporate triglyceride requires insulin and to keep insulin in the fat cell requires insulin to prevent lipolysis. And so on the one hand you say well this patient is insulin resistant will talk about which sells you know, maybe the muscle is insulin resistant, but at the very least looking at the fat cell it appears to be quite well in sensitive to insulin, right exactly and it's the same thing with de novo lipogenesis and that this is why I say we know that de novo lipogenesis in this state of insulin resistance is taking sort of glucose and turning into fat and then the liver sort of exports this fat as V LDL and triglycerides. Well, the thing is that if you have internal starvation of this liver cell, that is the glucose cannot get into this liver cell. How on Earth is this liver?
Going to package glucose and turn it into fat because we know that is happening. But where's this glucose? Like it's taking glucose making it into fat, but you're telling me if that with this Paradigm that no glucose is getting in your facing internal starvation. I mean, it's like making a brick wall with no bricks. It's just impossible. But yet this is the Paradigm that we face this internal starvation Paradigm and you look at the person like you look at a type one untreated type 1 diabetic where there actually is no insulin and they're like a stick. So if you ever seen some pictures these type 1 diabetics could not gain fat no matter how much they ate then they, you know, they peed out all the glucose then they died.
That's not what it looks like in type 2 diabetes and insulin resistance because type 2 diabetes is a disease of too much insulin resistance. So there's no way that is possibly true. So what you have to come up with is a different sort of a new paradigm of thinking about what insulin resistance actually is and this is one of the things that you know why I say physics always appeals to me because that's where you can come up with a new Theory which explains all these sort of paradox is much better and that is that it's not a sort of underfill problem. It's an overflow problem because there's two possible way. So we say their insulin resistant because the glucose does not go into the cell. That's the whole reason we say it's in some resistance locking key Paradigm. The gate is closed but there's actually two reasons why that glucose might not go into the cell because either the door is closed or it's already too full that is
If you have a cell that is already bursting to the seams with glucose that glucose from the blood simply can't get in. So this is a totally different Paradigm than this sort of internal starvation Paradigm because it's an overflow Paradigm, but it solves the problem of the central Paradox. That is why is this liver cell making so much new fat from glucose because it's jammed full of fat the glucose from the outside cannot go in but the liver cell is so busy trying to make new fat Novo lipogenesis. That is just shoving it out the door, but there's too much going in. So the problem is not insulin resistance per se the problem is hyperinsulinemia that is in the first place. It was all this insulin that put all this glucose into the cell, but you're putting so much into the cell that it's too full. I use an analogy like suppose you have a suitcase and you're putting your
In your suitcase, which is fine. And your wife says here put these shirts in you put it in that's fine. And then at some point your wife says here put these two shirts into your suitcase, but you don't put them in. Well, why don't you put those 2 T-shirts last two T-shirts into your suitcase either the suitcase doesn't open or it's just full there's two possibilities and they're completely different or to extend on that analogy. You could say, well you're just not listening to your wife what you're basically saying is look the conventional view here is when your wife said put these two shirts in your suitcase the last two times you just decided I don't want you know, I don't want to do that. But what if there's another approach what if you're fully well and willing to put those last two t-shirts in the suitcase, but when you open up the suitcase, there is simply no more room the output looks the same excess shirts outside of the suitcase, right, but the reason could be entirely different.
Exactly, but the implications are huge because the thing is that if it's just the fact that you're not listening to your wife and you're not putting the t-shirts in then the solution is for somebody to grab those 2 T-shirts and just shove them in right and that's what we did with type 2 diabetes because we said the glucose can't get into the cell. What we need to do is give you exoticness insulin. Sometimes huge doses of exoticness insulin so that we can shove the glucose Ram it down the throats of the cell. That's for some reason not listening to us, right but if it's an overflow Paradigm, the implication is completely different because the solution is to get rid of the some of the stuff that's in your suitcase, right? So if you bring it back to insulin resistance or hyperinsulinemia, then the solution to trying to get rid of this so called insulin resistance is not giving more insulin because that was the problem
In the first place putting those shirts in the suitcase. That was the problem in the first place. So putting more in is not the solution the solution is to get rid of it. So the solution is to empty that's a love glucose. That's the whole solution which is a totally different Paradigm than what we've been taught right because we use so far. No Yuri has we use insulin based on just trying to shove more glucose into this already filled cell and it solves a problem explains the Paradox of tell you the whole thing. There's a it actually goes much further, but it solves a problem of the central Paradox of why it's making testosterone why the insulin effect that the so high right? Why do you get PCOS? Why do you get the mitogenic effects of insulin the growth effects of insulin because you know that insolence of growth factor has huge implications for cancer. For example, so breast cancer colon cancer, very insulin sensitive much higher rates in type 2 diabetes and obesity. So you're getting the
Cancer causing effects of the insulin but yet you're saying people are insulin resistance the fat and the whole thing is solves the problem of why you're having continued de novo lipogenesis even in the face of this so-called resistance because you actually have too much. It's not just a theoretical thing. It actually has huge implications for the treatment because your treatment now has to be getting rid of the sugar getting the insulin down. So let's pause for a moment and talk about the treatment so you I want to just sort of synthesize this for the listener because what you're suggesting is quite radical, let's be honest, right? The conventional view is going back to your analogy which I love by the way. Is that after your wife asking you enough times to put more t-shirts and you stop doing it and the consensus view is you just stop doing it. For some reason you're not sensitive enough to her request. You're being an insensitive guy. Look that's an easy thing to understand you just an insensitive guy. Well, the current approach is your wife walks over and opens the suit
Ace and gets a few of her friends and your friends to help Jam those t-shirts in there because if you had enough people and you could put enough weight on the t-shirts, you could probably sneak a few more in right in other words, if you had more insulin or another analogy would be she yells louder is probably a better analogy. Right? So therefore polite request is insulin then raising her voice is more insulin than yelling and screaming and then by the end she's going to like take your favorite football and throw it at your head and at that point you're mainlining insulin into the patient. Let's talk a little bit about some of the other drugs because most of the approaches to type 2 diabetes pharmacologically are not actually aimed at reducing glucose metformin is one of the very few drugs, you mentioned the sglt2 Inhibitors sglt2 Inhibitors, which want to come back to so we'll carve out the ones that actually lower glucose but most of them are trying to amplify the noise. So walk us through the classes of those drugs so we have
So far, no Yuri has which stimulate insulin and there's insulin which stimulates insulin and the dpp-4 is for example, which are also similar in terms of the increased insulin. This is more than incretins, but they increase insulin basically so the classic response of the older class of medication, so I'm going to leave so metformin I'm going to leave aside because that's actually totally different thing sglt2 s is the sort of newest class but the old ones are all about increasing insulin. So that's your wife screaming louder at you to shove more shirts in and this is the thing. So if you do that, so say you give somebody a sulfonylureas and you start shoving more, you know, your wife starts yelling at you. So you start shoving more t-shirts and at first you can do it, but as you keep doing that the problem just keeps getting worse and worse because at first its little foal, then it's a lot to full and then what happens well, even if she's yelling at you really loud.
You still can't put anymore and because you've now you're just way over over the limit. So this is what happened in the body because look if we look at the way we treat a type 2 diabetes sort of twenty years ago. It was to give so far. No Yuri has an insulin than more insulin than more insulin your just shoving my shirts into that suitcase and the cell is getting more and more glucose and it's getting more and more full as it gets more and more full the insulin resistance gets worse and worse. So what do you do? You keep going up you keep going up and guess what? That's exactly what happened. But if you think about it, if you have a patient who 10 years ago was on one drug now they're on huge doses of insulin that diabetes never got better. The sugars might have gone better. Right but the actual disease itself of type 2 diabetes never got better. It only got worse and that's the reason we say it's chronic and Progressive because the treatment was completely incorrect we
The wrong thing we kept putting more shirts in when we should have been taking shirts out. We kept putting more glucose into the liver which is what insulin does right instead of taking all that glucose out of the liver. It was the wrong thing. That's why people got worse. That's why we could never show any benefit to tight glucose control and type 2 diabetes. That's why the Accord the advance the VA DT and all those trials failed because they're working on this incorrect Paradigm of insulin resistance. This is the lock and key Paradigm. So now we have a drug class which is something completely different. So this is the sglt2 before you go to that Jason. I'll just add another point to this because I know I discussed this with Jake Kushner several months ago, but it's important to revisit this in case folks either forgotten that or didn't listen to it. I want to emphasize what you just said a second ago because you said it's sort of like, yeah, we all know this but it's such an important point right when
Diabetes trials are using glycemia as their end point meaning. How low can you get the hemoglobin A1c how quote unquote tightly. Can you control the glucose? They do seem to have some benefits anything that is macrovascular does seem to get a little bit better. So we're glucose at high levels causes problems. Those things seemed to get a little bit better, but we're glucose at modest levels in the presence of high insulin. It's right at the micro. I said micro. I meant microvascular but the opposite is not true. So by taking someone's average glucose from 200 down to 150 that would be considered a huge win in a diabetes trial if you took their glucose from 200 down to 150 and that benefit might show up in their kidneys, but if you had to double the amount of insulin you gave them to do that. It turns out at the macro vascular level for example, heart and brain
They don't get any better. In fact, they might get worse. I remember the first time I sort of saw that about three years ago. It was a big aha moment, which is why aren't they getting better? And that sort of when I began to think about hyperinsulinemia itself. I mean, maybe it was longer than that, but that's not that long ago, right? It was like hyperinsulinemia itself is problematic if you normalize for glycemic levels, yeah because this is the thing that is not the blood glucose per se it's the whole body glucose because if you think about this overflow Paradigm now if you take the glucose that's in the blood and simply shove it into the liver. Have you done anything good for this patient? The answer is no because you're just covering up the problem. So you take insulin and your sugars are amazing right there normal, but you shoved all this sugar into your liver what happens when you stop taking the insulin all the sugar comes rushing back out of your liver and your
Those high so you actually have to keep taking it to keep it bottled up. All you've done is you've covered up the problem. You never made it better because it's like taking garbage and throwing it under your sink. You can pretend that your kitchen is nice and clean, but it's going to start to smell and that's the problem. It's the whole body glucose moving the glucose from one compartment of the body, which is the blood to another compartment which is the liver. So you move the glucose from where you could see it into somewhere where you couldn't see it. That doesn't do your body any good and that was the real lesson of the Accord Advanced vatt. That was 2008. Those are actually the trials that started me down this whole thinking that what we're doing is actually completely incorrect because if you remember for 2008, I've been doing this for like 18 years or 17 years and that was what we always thought right you get the blood glucose low enough or normalize it you're going to see huge benefits, but we didn't we didn't see
Any benefits at all? And that was a huge paradigm shift because these all came in 2008 and yet nobody wanted to propose a new theory of what is insulin resistance. And how are we treating it? And why are we so wrong? We just kept doing what we kept doing. We just said well, maybe it's the hypoglycemia. It's like come on that's stupid. They weren't getting a lot of hypoglycemia. But what they had to understand that that point which nobody ever did was that this Paradigm of lock-and-key internal starvation is completely the wrong way to think about it. Therefore you're using the wrong treatments you're using treatments that are actually going to make it worse not better and when you actually get rid of the glucose, so this is gets me back to sglt2 S. So the sglt2 S are a new class of drug and what they do is they actually make you pee out the sugar so it blocks the receptor on the kidneys where you're actually absorbing the glucose and you actually pee out the sugar so you get
Side effect you get tons of side effects you get like urine infections and yeast infections. And for some reason you get ketoacidosis to but the point is that if you look at the trials are actually quite consistent you actually get a huge huge protective effect from the sglt2 s that is for the first time in like decades. We have a drug that actually protects against kidney disease. So reduce the risk of kidney disease by about 25% and reduce the risk of heart disease, which we've never seen before in any class of anti-diabetic drug because what we're doing now is we're actually getting rid of the garbage. We're getting rid of the glucose were emptying out that suitcase. So the amount of lowering of blood sugar was super unimpressive in all of these trials. So there's like five or six trials now every single one of these trials shows end-organ protection with almost no benefit to your blood sugar.
K1 C with Drop Like .3 or point for like nothing. It was terrible for the blood sugar but the endpoints were incredible. Why because you're actually getting rid of the actual problem. You're emptying out the body of this glucose, which is what was making them sick in the first place as opposed to Simply moving it around and that I think is the explanation as to why a sglt2 s are so so effective for organ protection, which we never saw before because now you're actually treating the underlying problem of too much whole body glucose as opposed to Too Much glucose in the blood, you know, it's a totally different Dynamic like if your whole body has too much sodium versus just the blood has too much sodium. It's a totally different problem, right? If you have whole body has too much sodium you get edema. If you're just your blood has too much sodium you have hypernatremia two, totally separate problems. Same thing here if you blood
Is high and your whole body glucose is high totally separate problems. Now, we're actually addressing the underlying reason let's consider we're going to go to this in detail. So we don't have to go deep now on it, but just listening to the way you're describing it. It seems that another way to provide benefit which clinically seems to work quite well is exercise because the more one would exercise the more one would increase a different Reservoir outside of the liver, which is actually a larger Reservoir and in one that can't put its glucose back into circulation, which is the muscle. So as I listen to you describe this it's not inconsistent with this clinical observation, which is you take a person with type 2 diabetes who is not exercising at all who is sedentary and even if you make no change to their nutrition exercising them quite vigorously for an hour a day is actually
To have a benefit independent of anything else. Now the idea here would be how many of these things can you combine them? So what is the magnitude of that benefit? There is a benefit for sure. I mean we all the studies we've done on exercise or beneficial but much less efficient than attacking the diet just because liver is really the key to type 2 diabetes the fatty liver and all that sort of thing and you really can't exercise your liver. You can burn off a lot of this glucose with exercise but compared to the amount that you put in on a daily basis. It's a lot more work than to simply not eat for example. So in terms of efficiency is just less efficient, but clearly there is a benefit to exercise and it's the same thing. You're really just trying to empty out all this glucose from the system. The other thing is that what always strikes me sort of funny is that it's not really just about the diabetes. It actually affects more than that because it actually goes into the entire metabolic syndrome because if you think about it metabolic syndrome is
Constellation of five things. If you take the ATP definition It's The increased blood glucose, which we talked about but also abdominal obesity high triglycerides low HDL and high blood pressure and if you think about it, hyperinsulinemia plays a role in the same thing because what happens of course is that if you have this overflow Paradigm, this liver is now busy exporting out tons and tons of the fat right? It's got too much glucose because of too much insulin. So it's too much glucose too much insulin. So therefore the liver is jam-packed and it wants to get rid of all this extra fat so it's actually putting out tons of triglycerides. So that's why you get hypertriglyceridemia. And then of course as triglycerides go up, we know that HDL goes down. So HDL goes down as you're exporting out all of this fat the fat goes into all kinds of places where it's not supposed to go to the pancreas and to the oh, man.
Fat and you get this abdominal obesity not because of dietary fat because remember dietary fat doesn't go into the liver. It goes into the chylomicrons which goes into the blood vessels which just taken out by the adipocytes right never goes into the liver. It's the fact that the liver is pouring out all this new fad that gets taken up in all the organs around it. So you get fatty pancreas for example, which I wanted to talk about in a second but that's abdominal obesity. And we know that insulin has an effect on blood pressure because insulin causes reabsorption of sodium at the site of the proximal tubule. So now hyperinsulinemia too much insulin is really what is behind abdominal obesity high blood glucose high blood pressure low HDL and hypertriglyceridemia. That's the metabolic syndrome. The whole syndrome is not a syndrome of insulin resistance. It's a syndrome of
Hyperinsulinemia and that's a way better way to think about it. Because if the problem is hyperinsulinemia, and the solution is completely obvious. Insulin is high. How are we going to lower it right as no different than hey if your thyroid is too high you want to lower it if your thyroid is too low you want to give some well that's also hard to understand but think about type 2 diabetes for a second type 2 diabetes. We know that insulin levels are high. So, why did we think it would get better by giving more insulin? We totally misunderstand the problem. Yeah. I had a mentor who trained as an endocrinologist, but now focuses exclusively on type 2 diabetes and obesity. He said the exact same thing which is we have to he doesn't like the term insulin resistance for the same reason you don't which is he says it's not consistent with the way we think about under chronology in endocrinology. We think about hyper and hypo
When the blank and yeah, he uses the example thyroid right? He's like look if you have too little thyroid hormone, we give you more if you hypothyroid we give you more and type 1 diabetes is that analogy? If you have too much thyroid hormone, we don't give you more of it. We treat you in a way that reduces the effective it and you know, sometimes that means taking out part of the thyroid analyze other things, you know, it's funny. I think part of the the reason I think people struggle with this is the endocrine system is easier to replace than to shut down, you know for hypercortisolism. He has another great example, right when you have patients whose cortisol levels are unmeasurable and extreme example of that would be someone in an edisonian crisis, you know, we're pretty good at giving more cortisol, but when you have people with hypercortisolism Mia, which unfortunately comes hand in hand with hyperinsulinemia, there's no pill to lower hyper cortisol. Emia. Exactly. And this is the same problem we had that is type 1
He's which is too little insulin. Hey, it was great just give more insulin, but we had type 2 diabetes, which is too much insulin. There's no drug like sglt2 for a little bit. But before that there's no drug. So then we just gave the same thing. Right? It's so ridiculous. Just like giving a hyperthyroid patient a give them some elf. I Roczen right? It's like that's going to make it worse. But we did the same thing and we watch these people get worse. We gave them insulin and what happened they all gained like 30 pounds like every single study showed that dcct showed that right. They just gained weight and they became hyperinsulinemic. We have type ones who actually became hyperinsulinemic you start out taking 20 units 15 units a day when you're a kid and then you by the time you're 45, you're taking like 60 units a day why you developed insulin resistance and yet you had no insulin in her body in the first place 20 years ago, right because we thought that giving more and
It was good, but we didn't realize that hey too much insulin is just as bad as too little insulin or worse. And in this case and the funny part about it is that we actually know a lot about biochemically how this sort of overflow Paradigm works. So if you look at the glycolytic cycle and the TCA cycle, for example, you have glucose which undergoes glycolysis to pyruvate pyruvate goes through pyruvate oxidation into acetyl-coa, which undergoes the citric acid cycle which gives you citrate and gives you ATP which again, we know feeds back and blocks glycolysis like, okay. Well that's you have glucose. It goes into the cell goes undergoes citric acid cycle you get lots of ATP lots of citric acid feeds back blocks glycolysis, which means the glucose can't go in. It's like, okay, we worked out the whole biochemistry.
How this is Overflow Paradigm is supposed to work. We actually teach it to like high school students that hey if you're feeding in way too much of this stuff into the TCA cycle. There's a feedback there's a negative feedback loop and almost every biochemical reaction. Does this right in biology? If you start stimulating stuff you actually have something that's going to block it TCA cycle is no different ATP is going to block like call us this which is going to block that glucose. So you don't overload the system. That's what's happening glucose can't go in anymore. This is such an important point because then you can say okay hyperinsulinemia, which is actually too much glucose too much insulin is going to feedback and not let the glucose into the cell which is why the glucose stays outside and you have the so called insulin resistance, but the key is to empty out the cell of glucose how you're going to do that. Well low-carbohydrate diets in terms.
Fast there's no more potent way to lower insulin than too fast. I mean we're going to come to this in a moment, but I get such a kick out of watching people argue back and forth about whether carbohydrate restriction versus fat restriction is better at lowering insulin. My experience is that carbohydrate restriction does a better job than fat restriction, but I feel like sitting on the sidelines saying hey guys, there's another tool over here. You've both sort of Forgotten that's like infinitely more potent eat nothing and watch what happens to insulin levels and this is what we did. We just said, okay don't eat anything you gotta clear out this glucose. You got too much glucose in your cell clear it out. The easiest way to do that is eat nothing. Then you're going to force your body to start using some of this fuel. Right and the first place is going to pull it out of is this fatty liver? Oh by the way, the fatty liver so of course is driven by this de novo lipogenesis, which is why again, we see this huge correlation between fatty liver, which is a huge problem.
By the way, it's actually causing a ton of cirrhosis these days and type 2 diabetes because it's actually part of the same problem. But exactly you're completely ignoring your most effective tool which is intermittent fasting. As soon as we did that we saw tons of people just reverse their type 2 diabetes, which gets me to my next point which is the type 2 diabetes and everybody forgets that this is actually a two-step process, right? You don't develop type 2 diabetes just with insulin resistance. It's actually is two things you need one is insulin resistance or hyperinsulinemia, which is a much better name and then to you need beta cell failure because what happens is and this is where the old Paradigm was completely wrong again. So we said, okay. Well you have insulin resistance your body responds by increasing the amount of insulin. So we know that that happens we get hyperinsulinemia, and then eventually the Kang crius is just so tired of making all this insulin.
That it atrophies and it fails and that's beta cell failure. That's when you actually see the blood glucose go way up and this whole process takes like 10 years or so. So the rising of insulin resistance is met with hyperinsulinemia, which keeps the blood glucose normal and it keeps it normal for a long time at the expense of hyperinsulinemia. And this is precisely what crafts that you can figure it out much earlier. If you look at insulin levels as opposed to blood glucose levels, but the point is that now you have to hypothesize that there's two completely separate things going on one is insulin resistance and to is beta cell failure and they're totally separate and again, it doesn't make any sense. There's too many experimental points that don't line up one. We know that if you're going to say type 2 diabetics their beta cells have failed. Well, we know that's not true because
Virtually all type 2 diabetics are reversible. If you do bariatric surgery, if you look at the studies like 80% 90% of those type 2 diabetics, they actually get off all their meds. They actually reverse their type 2 diabetes. So if you said that the beta cell just failed then you're wrong because even the most severe type 2 diabetics reverse, we have three year. Also the youngest person in the world to get type 2 diabetes was three years old you're going to hypothesize that this three-year-old pancreas has failed has atrophied like that's clearly wrong. And the other thing is that you have to say if these two things go hand in hand. Why is it that you only see beta cell failure in this case of insulin resistance and never anywhere else. Like how does that even work? Like, they go together one goes with the other all the time and exclusively with each other. So this is the point that you'd have to say that there's two separate things going on, but if you think about the sort of
Paradigm again explains this Paradox very easily because what happens is that and this is where you know, if you look at a lot of the work on the Twin cycles hypothesis fits in is that you're filling up your liver with all this glucose hyperinsulinemia. You got too much glucose in your liver your liver starts making fat and pumping it out. Then one of the organs that do it accumulates in is the pancreas. So now you've got fatty pancreas and that is the problem is that your pancreas is not fail. Your pancreas is just clogged with fat and you can measure these in an MRI and whatever and you can see that all these people who have type 2 diabetes actually have big fatty pancreas as well. And as you simply get them too fast, so the Counterpoint study which was done by Royce Taylor and so on they showed that the type 2 diabetes was reversible because you simply unclog the fat but now the fatty liver is responsible.
For the insulin resistance or hyperinsulinemia, and the fatty pancreas is responsible for the beta failure. So they're both manifestations of the same thing. They're both manifestations of hyperinsulinemia and that explains why it's not to defects of type 2 diabetes is actually a single defect and why it's a reversible problem. So again this hypothesis fits the anomalies so much better than everything else and you know, if you look at fructose, for example, it's like why is fructose so bad and it's like, well, it doesn't have any glycemic effect. It really doesn't have that much of an instant effect that causes law this fatty liver, right? All that fructose goes into the liver gets turned into fat no more lipogenesis. Now, that's all part of the same pathogenesis the fatty liver the hyperinsulinemia. So explains everything about how this disease of type 2 diabetes more than just hyperinsulinemia are
Some resistance explains how that all kind of comes about it sort of fits a lot better. And this is what I mean, but that's why I like the physics model which is like, okay. We have a theory now which no fits the facts so much better than the old lock and key model and therefore you have to adopt it and say what are the treatments that come out of this that are going to be more effective the actually two separate things I want to ask about. The first one is do you see a way that nafld e is causal towards hyperinsulinemia and separately where hyperinsulinemia is causal to nafld e the literature is really not clear on this and you could just say well, let's just dismiss the literature out of hand, but clinically these things are so tightly wound and I've never really done the clinical experiment to tackle one without the other. So it's a very common presentation is hyperinsulinemia that you described.
Also move big fan of Joseph craft and actually I would credit it to Nagi Torbay who was one of my mentors the endocrinologist. I referred to who really got me to think of it as hyperinsulinemia as the endocrine condition and and his view was look the oral glucose tolerance test with frequent sampling is our best tool because long before glucose levels get out of whack you're going to see in appropriate amounts of hyperinsulinemia early on but nevertheless the common presentation is patient has hyperinsulinemia weather without normal glucose levels during their hemoglobin A1c is often completely normal. They're alt is high much higher than we would like it to see though not so high that people would get alarmed by it. And if you really felt like doing it and you were resource unconstrained you could get an ultrasound of the liver and you would almost assuredly see the accumulation of fat.
Well with that patient we take a treatment plan that addresses both the nafld E resolve the lfts within a very short period of time normalized and so too does the hyperinsulinemia and so I've never tried to disentangle if the high level of insulin is really pushing the fat accumulation in the liver or the other way around although of course, you could argue that there's different scenarios, right? If you put somebody on a very high fructose diet that wasn't necessarily overly abundant in glucose. It might actually be that the nafld e drives the hyperinsulinemia versus a diet that is too high in carbohydrates for the individual such that it's the hyperinsulinemia that ultimately leads to what helped me think through the the arrow of causation in the other direction. Well, I think I think it does both right so you have those Studies by have L from 2009 where he took people and gave them a lot of fructose, right? So the experiment was great.
Took people two groups of people one. They gave sort of Kool-Aid that is sweetened with glucose and one that they gave Kool-Aid sweetened with fructose and then they actually looked for insulin resistance and so on and what they found was that when you gave a lot of fructose people got type 2 diabetes, you could measure the oral glucose tolerance test and they actually became diabetic. So what you see is that the fructose which is metabolized in the liver is causing this fat accumulation specifically in the liver and that is going to cause a hyperinsulinemia, right because the liver is full of you know, all this excess fat now, you're trying to shove all this glucose into this fatty liver cell in the livers like no I can't take anymore. So I'm going to be resistant to this. So as it gets resistant the blood glucose goes up and the body starts to have to make more insulin to soar get rid of this other situation, which is a haters too much glucose in the body. So I think the arrow of causation
It goes both ways, which means it's sort of a vicious cycle each is making it the other worse. So you have to take care of the problem. So when you take care of one you sort of take care of both and I always say that what's interesting is to look at this way of thinking and then think about if you take it sort of one step further what you see is that the Obesity the insulin resistance and the type 2 diabetes, which is a fatty pancreas as well as they're actually not detrimental. They're actually protective. They're actually mechanisms of protection against the problem. So for example, let's take obesity. So I say Okay. So let's think about this one step at a time suppose. You have houses on a street and Insulin every day, you take a little bit of sugar so bit of glucose and Insulin comes by and knocks on the door and gives you a little you know, a little bit of glucose and you say thank you and you use it for energy and everything's great. Now all of a sudden you start taking a lot of glucose so insulin comes
And instead of giving you a little cup of glucose, it gives you a big barrel of glucose and it's sort of like too much right but you take it because you're supposed to but eventually, you know your house fills up with all this glucose. So after a while the glucose keeps coming in and Insulin keeps giving you a big barrel full that you can't use every single day and now your house is full. So what are you going to do? Well, you're going to stop taking that glucose. So that's insulin resistance. So that's not actually that's a protective. It's protecting itself from the effect of too much glucose. That's what the fatty liver is doing. Its protecting itself from too much glucose. It says, hey, I can't take any more of this. So what happens of course is the insulins like, oh I got to get rid of this glucose, right? I can't have it hanging around. I'm going to lose my job. So it gets more insulin and starts battering down the door and just shoving in all this glucose not that glucose is bad, but there's just too much of it. So it just keeps shoveling in it.
So then you're overcoming that protective response the Obesity which is the filling up of your house was actually trying to protect yourself against this excessive insulin resistance and we see actually evidence of that in the lipodystrophy these so I don't know if you saw that paper a few years ago about lipodystrophy. So you had these people that actually had no fat and you think okay if they're so thin if they're so skinny. They must have no insulin resistance. They had the worst insulin resistance you've ever seen like off-the-charts. They wrote about it in the New York Times. Yeah. This is the thing that sort of explains that Paradigm which is if you are truly insulin resistant and you at least buy the argument that that's a global term meaning one cell is insulin resistant. They all are well then. Yes, you should be the leanest individual on the face of the Earth because your adipose tissue does not have the ability to integrate or assimilate the signal that says one bring triglyceride in
And to Halt the process of lipolysis the problem is not insulin resistance per se. It's actually hyperinsulinemia. So what your body is doing is taking all this fat and sort of storing it away. So it doesn't cause a problem right? So these these people with the lipodystrophy they couldn't store the fat. So what happens is that the fat stored up in their liver and they had the highest insulin resistance you've ever measured because it's really a protective mechanism. The fat is trying to suck away all this glucose so that it doesn't cause a problem. This is why obesity itself is actually a protective mechanism against hyperinsulinemia against too much sugar. So the ultimate problem is too much glucose and too much insulin. So then the next step is okay. So now insulin sort of is way too much the insolence got all his cousin's out, you know, battering down your door throwing in all the stuffing can't take it anymore. So then what do you do while you start to take some of these barrels and try and give it to like your friends?
Family and so on right? So this is what the liver does right. It's got way too much fat sitting around. So it takes this fat and shovels it out the door as vldl and it goes into the other organs. So it goes into the pancreas it goes into the liver goes into your omentum. That's how you get the Obesity the abdominal obesity that you see so now you've got obesity as a protective mechanism and insulin resistance itself is a protective mechanism because it's the cell is trying to protect itself from too much insulin too much sugar. The last part is that you're throwing out all this glucose into your pancreas all this fat and your pancreas your pancreas stops. It makes a lot of insulin makes a lot of insulin makes a lot of insulin up on to a certain point now it's all clogged up and it can't make the insulin. So what happens? Well, you start to pee out all this sugar right you get the polyuria polydipsia glycosuria. Your body is actually trying to protect itself by peeing out all this sugar.
Here so it's like you have to look at it. The other way we think of all these responses obesity insulin resistance and the the beta cell failure as pathologic. They're actually protective. It's a totally different thing. Your body is actually trying to protect yourself against the root cause of the problem which is too much insulin too much glucose. So when you enhance that glycosuria with sglt2 s guess what you actually have a protective like a hugely protective effect because that's the protective mechanism against the root cause when you actually give people more insulin, you actually keep all that inside then what happens to gain weight and clinically you see this clinically to the patient's know it because you give them insulin their blood sugars are better, but then they gain weight and as they gain weight their diabetes gets worse, so you give them more insulin and is given more insulin. They gain more weight. Do you think that adiposity per se all things equal?
Is also driving the hyperinsulinemia and if so, what is the mechanism or do you believe that the adiposity is a bystander of it because this is also an enormously difficult problem to tease out in clinical trials because virtually any clinical trial that demonstrates an improvement in quote insulin resistance or more accurately a reduction in hyperinsulinemia is without exception to my knowledge accompanied by weight loss and a reduction in adiposity and this to then drives a causal question, which is is the adiposity driving the hyperinsulinemia. So let's for a moment pause it that hyperinsulinemia is the way we will refer to this and we won't talk about insulin resistance because that turn has really lost meaning in this context that the adiposity is driving the insulin resistance or the insulin resistance is driving the adiposity. I think it's more likely that the hyperinsulinemia is
Driving the Obesity rather than the other way around. I mean it's always hard to tease out but you can look at to me. It's always like let's take sort of an experiment and see so there is a great experiment a few years ago where they took people who were type 2 diabetic and is in the 90s and they gave them a lot of insulin. So from time 0 to 6 months, they went from zero units of insulin to like a hundred units of insulin that blood sugar's were great. And what happened? Well, they gained like 20 pounds and if you look at the number of calories that they were eating per day, it actually dropped by about to 300 calories per day. So what you see is that the only difference because this was a randomized sort of trial. The only difference was the hyperinsulinemia. That's what we change when we change experimental e the amount of insulin people were getting because we're giving it to them they gain weight. So to me that is clearly a causal relationship.
We see this all the time. Are you prescribe insulin people gain weight, you give sulfonylureas which increases then people gain weight, right you give them sglt2 is which make insulin drop then you lose weight and type 1 diabetics know it to like they lose weight. So the arrow of causality is very easy to establish going from hyperinsulinemia to obesity and forgetting all the mechanism. The all I'm saying is that when you give insulin people gain weight every single time you give insulin or raise it by sulfonylureas or when you lower insulin with type 1 diabetes, they lose weight and it doesn't forget about what you eat or whatever like people always say. Oh, let's put equal calories in that like free like all I'm changing is the insulin then obesity goes up or down depending on what happens to the insulin. It's much harder to establish that causality the other way around right you can and they've done this with liposuction. So if you take a situation where you remove 20 pounds of fat
What happens in the answer is nothing right now? That's study if you're referring to the one that Sam Klein published in the New England Journal of Medicine. I love that because it's a great example, of course to push back is yes, but that was only subcutaneous fat that was removed. We don't do liposuction on visceral fat, you know on some level. I think this is a great theoretical question. It might not matter. In other words. It doesn't change the clinical decision. It's an important question is we think mechanistically about what's happening, but it doesn't change what you do with a patient which in the final analysis matters more than anything but yes until we can really do liposuction on visceral fat, which I personally think would just pose too much risk to justify. It's going to be very difficult to tease out the other direction. But what about the role of inflammation because the other thing that seems to go hand in hand with hyperinsulinemia in patients is they also tend to be quite inflamed and we can measure
This non-specifically with things like C-reactive protein fibrinogen interleukins. We can even see cardiac specific forms of inflammation. So for me, this is just a very non scientific clinical observation, but I'm curious as to whether you've seen it. Yeah, in terms of inflammation again, I look at it from an experimental standpoint. So if I think inflammation causes obesity, for example and what happens when you decrease inflammation because we have anti-inflammatory medications what happens to obesity. Well, you can give NSAIDs and people don't lose weight. You can give prednisone which is probably our most powerful anti-inflammatory people don't lose weight. If you give all these antibodies this antibody that end, you know, there's all kinds of inflammatory il-2 and tnf and you have all these things other than if they get super nauseated they lose weight, but if they don't get super nauseated then they don't really lose weight. So to me that whole story
Might be a kernel of Truth in that but to me, it doesn't really make a lot of sense. Like if you get a really bad infection, you know some kind of inflammatory state. So inflammation goes way up rheumatoid arthritis. Do you gain a lot of weight? It's like yeah, I don't really see it as opposed to the consistency where you give insulin people gain weight you take away and slim people lose weight to me. That's a consistent causal relationship. There is inflammation. It's much less like I don't deny that there's a lot of important inflammatory mediators and stuff but it's just not so simple that you can say more inflammation causes weight gain less inflammation causes weight loss therefore treat everybody with Advil or something like that. Yeah where it was going to go was actually slightly more nuanced which is again getting a little bit ahead of where we're going to go because I want to start talking about some treatment ideas, but you take a hyper insulin emic patient with no inflammation in my limited experience. They
And to respond quite well to carbohydrate restriction and exercise.
When I take patients who have significant hyperinsulinemia, but it's also coupled with inflammation. I don't find that they are as impacted by what I just said and I find that those are the patients that initially got me to start exploring significant periods of fasting either significant 500 calories a day for five days that type of fasting or you know water only for three days five days that sort of thing and again not a very scientific organization or observation rather. These are small n clinical things that I see but I wonder if a you've seen that and B if it's suggest that inflammation can have a sort of negative Synergy with hyperinsulinemia. I think that there probably is something to that because there is I mean for sure other hormones are involved like we know for sure there are other hormones involved. So look at cortisol, for example inflammations difficult because
There's so many different mediators, right you can have tnf you can have a tile to you can have all kinds of inflammatory mediators endotoxin and stuff but there for sure other hormones that make it really are very important like cortisol. So you've cortisol people gain weight, right? It's not as much as with insulin, but you give prednisone and you know, we've all done it you give prednisone you gain weight when you take away the prednisone like they finish their course of Prednisone that way kind of goes back down. So we know that cortisol for example is a huge impact on body fatness. For example, we know the studies from sleep if you get good sleep, you're more likely to be a good weight. If you are sleep-deprived, for example, it's a stressful situation where cortisol is going to go up then you're more likely to gain weight. So that's not an insulin thing. It's of cortisol thing. We know for sure that sex hormones have to play a role somewhere in there as well because there are women
Develop gestational diabetes and their insulin their diets. They don't change the difference is they got pregnant? Right? And that's a difference in sex hormones and somehow that impact and I actually don't know how this works, but somehow it does impact the response of I'm not sure they're hyperinsulinemic either. I think there must be something completely different about that entire thing, but it's not as common so I don't I don't think about it as much or girls and boys at puberty for example, the difference of girls and boys is testosterone versus estrogen for the most part. It's not an insulin difference yet girls we go through puberty have way more fat than boys. You get more muscle so we know that there are other hormones that clearly impact so it's not just about insulin but it's about cortisol is about sex hormones and I think inflammation probably comes in there somewhere but what to do about it and it's a lot Messier inflammations a lot messier than thinking about cortisol, for example
Where you can measure levels and you can think about Opera down, you know cortisol. For example, you have the too much which is pushing this disease. And what's the sort of Hallmark well obesity and then you can get too little too little cortisol is Addison's disease and what's the Hallmark weight loss, right? So again very very clear. It's easy to measure inflammation. It's just so hard. It's just too many moving parts for me. Yeah. I think this whole thing is too hard for me, but let's talk a little bit also about the role of hyperinsulinemia specifically on the vascular system. What is it about hyperinsulinemia and the endothelium or the capillaries that seems to wreak havoc beyond what tends to accompany late stages of it, which is hyperglycemia, which of course has significant damage mechanically on the micro vascular system. But what about like, for example, why would hyperinsulinemia exacerbate coronary?
Artery disease absent abnormal glucose levels or even once corrected for lipid levels, which I you know that observation exists, right? You can take patients that have the same lipid levels the same glucose levels, but the hyperinsulinemic patient is going to have worse cardiovascular disease. Why is that for that specifically? I don't know. I think that there's a lot more work because a lot of people still don't think about it as a disease of hyperinsulinemia, but I think of it generally in terms of two things. So I think about two things like cardiovascular disease a lot and cancer because those are actually the two top killers of Americans is CV disease and cancer and they're both to me diseases of too much growth. That is everybody thinks growth is good, but growth in adults is generally bad like you don't want to grow once you reach adults eyes. Your liver doesn't grow your kidney doesn't grow you shouldn't be growing and if you are growing it's generally bad. So if you
Wait, and you'll be seeking fat that's a disease of too much growth. If you have big fatty liver, that's too much growth. If you have all this excess protein in your brain, that's blocking your signals and that's Alzheimer s disease that's bad. And it's the same thing cancer disease of excessive growth in the blood vessels. We know that there's excessive growth right? It's not a matter and this whole idea of fat or cholesterol clogging your arteries like a pipe. It's super like even when I was in medical school, we knew that was not the case. We know it's a response to injury. That's why you get it at bifurcation points for example, and you get smooth muscle proliferation and then the foam cells which go in and it's not clear whether the foam cells and all that is a response to the injury, but it's because of that whole Cascade that atherogenic Cascade it's a response to injury, but you get excess proliferation of certain things including smooth muscle cells and so on but to me, it's just the
He's of too much growth that's eventually building and Laps and closing off that artery. And this is where the disease is of too much growth is linked very tightly to insulin because insulin is a growth factor. I mean, this is one of the things that is super exciting in cancer. I'll tell you like the peel pi3k thing because it directly links insulin which we all think about in terms of metabolism to growth every single time that you have a nutrient sensor like insulin like mtor like ampk it's the same insulin the pathway that it goes through which goes through pi3k and then like map k&a Katie is it influences growth increases growth and that to me is one of the big problems with insulin all the time is that you're telling your body to grow all the time when it
He shouldn't be growing all the time. So you actually have to decrease growth. If the problem is too much growth you want less growth and one of the things that you want to influence is insulin and mtor mtor. I know you talked a lot about mtor. It's the same exactly the same. It's a nutrient sensor at heart. It's very sensitive to dietary protein and what it does is if there's a lot of protein you turn on all these cell proliferation signals when you have very little protein what happens that's Hoffa G. It's like, oh, okay. So you have to realize that metabolism and growth are exactly the same thing and it has even more implication for cancer, which is a disease of too much growth. So being obese, for example, it doesn't give you cancer, but it certainly increases your risk of breast and colon cancer by a whole lot. There are 13 cancers that are listed as obesity related and
I know that there's a very strong relationship between Type 2 diabetes even without the Obesity but because they're hyperinsulinemic. There's a very strong relationship between Type 2 diabetes and breast cancer for example, so to me, those are all diseases of excessive growth and therefore you have to start looking at growth Pathways, which actually are the exact same as metabolic pathways, which is insulin mtor ampk, which is important of course for metformin and then all of a sudden you see hey all of these times that you can decrease nutrients sensors that is decrease mtor decrease insulin increase ampk you're getting good effects for longevity. This is fascinating. Yeah. Yeah, and it's so funny you say this Jason. So this past week I was in Boston and I was meeting with a number of folks and one of the folks. I was meeting with wrote a paper the very interesting paper in 2006. I was not aware of it at the time. He wrote a
Theoretical paper so it was a paper that got rejected by virtually every Journal out there. But in 2006 he proposed theoretically that rapamycin would be a great longevity drug. Now today we'd say well that's obvious but it's important to note that the first trial demonstrating the immense power of rapamycin to promote longevity was not published until 2009 three years after this paper was written and what he said was based on all of the evidence. He had examined to date of the use of rapamycin even in patients with transplant. It's antiproliferative properties alone speak to this and it's so funny to hear you. Say what you just said because he said the exact same thing. He said think about it Peter every chronic disease is some amount of hyperproliferation hyper growth
And you have a drug here that in the most elegant way in the least toxic way in the most specific way targets one of the most important Regulators of growth. His prediction was this is going to be the most important longevity drug there is and you know, I would agree with that in 2019. I think that there is no more promising agent than rapamycin for longevity. But again, it comes back to this growth thing and to put another bow on what you said. It was certainly lost on Me In Medical School how anabolic insulin is. In fact, I remember learning many years later that body builders used insulin and I remember thinking oh that's odd. I wonder why and of course after speaking to some body builders, you know, I got to learn well look testosterone is anabolic but insulin is even more anabolic now, you can't go overboard and this is where these hormones are very sophisticated because testosterone is very anabolic to muscle which
Insulin is as well. But testosterone is catabolic to Fat. Whereas insulin is anabolic too fat and anabolic to muscle cortisol. Just to bring It full circle is the worst of Both Worlds hypercortisolism. Mia is catabolic to muscle while anabolic too fat. I usually end up drawing this picture for patients on the Whiteboard showing estrogen testosterone cortisol insulin, and then you know, you draw a muscle cell a fat cell and it very quickly starts to paint the picture that says this whole thing is just Endocrinology. I mean all of this comes down to how can you manipulate these hormones to the desired outcome nutrition being one tool, but exercise the use of hormones themselves, of course in cases where there's deficiencies being another way to do it. So it's a very interesting way to sort of frame this as did the things that we care most about avoiding if you really look closely involved.
Of some measure of hyper proliferation and growth. Yeah, because that's the chronic diseases today because there's been a huge shift in the diseases that we treat. So if you go back a 50 years a hundred years you're talking about treatment of infectious diseases right hepatitis virus and pneumonia isn't diarrhea's and all this sort of stuff and we did gray. We developed all these great drugs antibiotics antivirals, like like really really good stuff and they haven't been as big a problem. Now, we have a problem with resistance of course, which is actually the same thing interestingly enough. I think there's a huge parallel between antibiotic resistance and insulin resistance. And in that they're the same thing antibiotic resistance is not caused by some Phantom things because by using too much antibiotic insulin resistance is the same thing. It's caused by too much insulin. So you have almost the same thing where antibiotic resistance is caused by too much antibiotics and we try and treat it by using even more.
Biotics right to overcome that resistance which is the dumbest thing you could do in insulin. We have insulin resistance. We treat it with more insulin, which is what caused it in the first place and then things get worse and we know and understand why so, you know that treating antibiotic resistance is about using less same with insulin, you gotta use less. But anyway, we shifted from using from treating these diseases which are infectious diseases to these chronic diseases, but we never change their Paradigm of medicine, which is the Paradigm was you come into me as a doctor. I give you a pill an antibiotic and you get better then people came in with these diseases like diabetes and obesity and the related diseases of hyper proliferation or I call them diseases of too much growth cardiovascular disease and cancer and all this other stuff too. Like it's all about fibrosis, right which in the end is just about you've revving the system too hard, but it's basically hyper proliferation and then we said let me give you a pill it's like that's totally the wrong thing because you don't
Have that pill to decrease proliferation rapamycin might be one but rapamycin to me is limited because you've got not one problem. You don't have one nutrient sensor. You have three nutrients sensors. You have insulin you have mtor and you have ampk it's a very sophisticated system look insulin response to dietary carbohydrates and dietary proteins m2r responds mostly to dietary protein ampk as actually like a, you know measures the ATP the MPAA TP ratio, so it actually doesn't care what you eat. It just cares about the cellular energy availability. So they're all three measuring different sort of things and they all work on different time scale. So insulin goes up and down within minutes. It's gone with an hour's mtor is sort of up and down between 18 and 30 hours and ampk is sort of days to weeks. So you have such a sophisticated system because you have three nutrients
Just that giving you different information based on your diet and also based on your time scale. So your body actually get such incredible information just by integrating which one is up and which one is down rapamycin only affects the one whereas some things hot, like intermittent fasting is going to decrease your insulin is going to decrease your mtor and increase your ampk, which is all three things that you need to do in order to sort of decrease proliferation because you know that all three of them insulin feeds into mtor and ampk also feeds in they're all part of that. Same thing. You're affecting three different parts of that pathway as opposed to 1 and that is going to give you the best bang for your buck and it's free and you can do it anytime you want and it's like, oh, hey, they told people this 2,000 years ago, right? When all the religions said. Oh you should fast and you should do this and you should do that, which is to me this sort of just incredible that you know it.
Come sort of back to what we knew two thousand years ago, which is that hey fasting every so often has incredible benefits because you're going to be able to affect those diseases of excessive growth. Let's pivot to this. Now. Let's talk about fasting it you and I are certainly to folks that are no strangers to this anyone who's been cared for by you or anyone who's been cared for by me pretty much is used to the same drum beat, which is I mean, I don't actually I'd like to hear about how you do it in our practice, you know, generally for the first year. We don't push too hard on the fasting thread, but boy by the end of that first year and into their second year with us. We're really having a hard discussion about this in some cases for patients that are resistant. Now, I have this sort of framework that I think about her fasting which is you start out on this sort of crappy standard American diet and how do you escape that gravitational pull of that horrible thing? I'll be sensitive and called the standard crappy diet the Canadian crappy diet or whatever as well. They're comparable to me the two.
Two easiest ways to help patients escape the gravitational pull of pure garbage is time restricted feeding and or some measure of dietary restriction so that the way that I explain that as timer circuit feeding says ostensibly you don't restrict what a person eats you just restrict when they men or do you restrict how much for that matter but you just put a feeding window on and you say look for 16 or 18 hours a day, you'll consume nothing and you will eat ad libitum in the remainder of that period of time and you contrast that with dietary restriction, which we've already alluded to carbohydrate restriction is a form of dietary restriction and it can come with and without caloric restriction, but the simplest way to execute it would be to say look no restriction on when you eat no restriction on how much you eat. You just can't eat these foods and that's sort of where the majority of the diet Wars live. Is you a vegetarian. Are you vegan? Are you on a low-fat diet a Mediterranean diet paleo diet low carb diet a ketogenic diet. They're all forms of dietary.
Restriction and to my knowledge. I'm not aware of one of them.that is not significantly better than just being on the standard American diet. So that speaks probably less to their individual efficacy and more to the abject misery metabolically that is being exerted on people before we get into fasting. Let's get everybody really dialed in on those two things time restricted feeding plus or minus dietary restriction. How do you visit those two things before we get into fasting I focus a lot more on the fasting. So I've always said yeah, it comes down to that the when you eat and what you eat and this was the thing that I sort of pointed out years ago like three four years ago, which the everybody focuses so hard on the what to eat and nobody talks like ever about the when to eat that is there is a sort of consensus. It was never intentional that we should eat all the time right? You should eat six or eight times.
Daja, Grace throughout the day and you know, there's all sorts of reasons that were made up to suggest why we should be eating six times a day, but there was never any science, right? So, you know, if you ever look back and say hey, where did we get this idea that we should eat six or eight times a day. It's like from nowhere. Somebody made it up its stock and that was about it. Right? It didn't there was no studies. There is no randomized control trials. There's nothing somebody just thought it was a great idea and a few years ago. I said the same thing which is that hey, we're sort of missing half of the problem because if it's two problems when to eat and when to eat and you're nobody's talking about when to eat then you're not going to succeed no matter what you do and let this is why there is this sort of diet Wars. I wasn't that interested in getting into that. I was like more like hey, let's look at this whole other problem. So what we do generally is start with that because it's a lot easier to change the frequency as opposed to what it is. They're actually eating and this just comes from experience. So the first thing I
Did when I started really focusing in on diet was try and change people's diet, but I did it from a clinical standpoint. That is I'm not seeing one person sort of for an hour every week. I have a clinical practice which means you get like 10 minutes like every three months so it has to be something that is sort of easy to understand and super effective as opposed to sort of counting carbohydrates or something which takes a long time to explain to somebody and then explain why eating fats not that bad for you and so on I needed something that was sort of much more efficient in that way and that's why we started using fast and quite a lot because it's something that people sort of understood you can explain it within the 10 minutes and then you can follow up with them and see if they're eating and they know sort of what it means to be fasting as opposed to some of these people who really didn't have any idea what a low-carb diet really met. And that was the issue. Tell the story again. I remember last
Are you were telling me a funny story about and I don't remember what the ethnicity was in the point was not to poke fun at one ethnicity or other. It was just like within this culture to say Don't eat carbs meant. Okay. Well, I won't eat bread or pasta but I'm still going to eat lots of noodles and lots of this and lots of that and they came back in and you said how's the carbohydrate restriction going and they said oh, it's fantastic. Dr. Fung I'm doing so well great. What are you eating? And it was like all carbs. It was just different carbs and that and that was I remember you describing that being sort of an aha moment of culturally, it can be very difficult to get people to restrict carbohydrates. Yeah, because it's their traditional food. So is I guess I have a lot of Asian so both East Asians and South Asians, of course, the diet is based on rice and rice noodles. And you know for the South Asians is rice again, so there's a lot of cultural difficulty which is why it was very difficult to sort of push too hard on it. You can if you if you make enough of an
Effort and I think that message anyway is getting across that eating all these carbs are are not great for you these refined carbs, but the point was that you have to still come up with something. This is where the Practical experience sort of comes in like you can't just say, okay. Well, I'm just going to stick with carb restriction right? I'm going to put these Chinese and Filipino and South Asian Sri Lankan people on no rice. No noodles ketogenic diet. They might say yes, but they actually won't do anything to you know to follow it because it's just so difficult right there. Their culture is like that they've been eating this way for 70 years and it's very hard for them to change and their family eats like this. So it's like what are you going to do as opposed to fasting which to me was a much simpler idea that was already embedded in every culture. So you talk to Muslims about in there. They're all like ha ha I know what you're talking about and you talk to Catholics and you talk to you know, Jewish people like they will aha. This is our Greek Orthodox or whatever and they're all like ha ha
And the Buddhists were like a ha so it was way easier just from a practical standpoint. That was where I started using it. And then I saw it like these crazy like crazy good like results. It was like insane. So we wrote a case report that was published in the bmj case reports. It was three patients who had like sort of 20 to 25 years of type 2 diabetes and like five years of insulin on big big doses of insulin. We told them about low carb diets, but you know, we don't spend a lot of time but we put on 24 hours of fasting three times a week, which is like a one meal a day right nothing too strenuous or anything. We got off all their insulin like between 5 and 18 days. It was ridiculous how quickly they responded and years later. We still have people who are all like non-diabetic. They went from 20 years of diabetes to non-diabetic and I maintained it for the last six years. It was ridiculous how good like I just couldn't believe the results that we're getting and that's when we were like, okay, let's
Tell people and let's start writing about it and all this sort of stuff and it took ages to get that it took like two three years to get that case series published by the you alluded to bariatric surgery earlier and about five years ago. I was involved in an effort to do a clinical trial to try to tease apart the observation you alluded to which was that when you take a patient with type 2 diabetes who undergoes bariatric surgery at the time, I believe this was true primarily for the roux-en- Y gastric bypass. So for the listener, that's a surgical procedure where the part of the bowel that comes out of the stomach, which is called the jejunum is the first part after the duodenum you cut a piece and then reattach it as a piece of a y and then bring it up such that you are basically bypassing not just significant parts of the volume of the stomach as a reservoir, but also the initial part of the duodenum and the jejunum
Observation was the following you do this operation on a patient within about 10 days. They haven't lost a meaningful amount of weight. But all of a sudden they don't need insulin anymore and very quickly their diabetes resolves. In fact, I believe we are still at a point. Although this may be changing. We're the only treatment that is viewed by an insurance company to actually reverse type 2 diabetes is bariatric surgery. So the question we were trying to ask was how would you design a clinical trial to parse out? How much of that is due to the change in the internal architecture. Is there something problematic about the duodenum of that patient? How much of that is due to the change in the nutrition of the patient because a patient who undergoes a gastric bypass has to make significant changes in their nutrition and how much of that is due to the perioperative period of
Caloric restriction so what's your take on those patients? Which again pretty profound results again? Not that profound. I think when you consider them in the context of what we now talk about with what fasting can do but what's your take on that my take is that the fasting does everything so you can actually get I think exactly the same result if you simply didn't feed them for 14 days or something like that because the thing is that when we do this for people you put people on a 7 or 14 day fast, we see this we don't do it a lot because generally they're older so you want to be a little bit more sort of regimented and there's also these cases of late onset type 1 and so on but you actually see exactly the same thing where the diabetes complete was up resolves. And and the thing about it is that you can understand it perfectly my understanding this sort of overflow Paradigm because what you're doing of course is dropping insulin levels very low, and then you're forcing.
The body after the first 24 hours glycogen runs out. So now you're going into a period where your body is going to have to metabolize fat for energy. So the first place it's going to start pulling it out of is going to be the internal organs because it's right there. The liver is going to be the first place that is going to start pulling the fat out of and if you look at Royce Taylor's data what you see is that the liver fat starts to go down right away the insulin resistance starts to go down right away because that's the problem right? It's this big fatty liver, which you can't shove any more glucose and that's what insulin resistance is as this big fatty liver goes down just like emptying your suitcase the insulin resistance starts to melt away and slower because he showed this incredible data which looked at pancreatic function with ultra-low diet. It wasn't fasting but as an ultra low-calorie diet, you can start to see that the pancreatic fat starts to go down because the
Is not pumping out your liver is not pumping out fat and dumping it in your pancreas. And as you get rid of that pancreatic fat your unclogging the pancreas and you're producing enough insulin that you don't get the hyperglycemia anymore. Your glucose isn't that high? Because now you're at a stage where insulin production is going to go up because they measured that and Royce Taylor's Counterpoint study the one from UK and you can see that the first phase insulin response starts to go up. It takes a few weeks, but that's exactly what you see. Clinically that is before you lose the weight which is all a lot of sort of subcutaneous fat. You're getting rid of the visceral fat the fat around the organs which is the heart of the matter. The insulin resistance is fatty liver. The beta cell failure is fatty pancreas, you're getting rid of that first and that's why that diabetes goes away so quickly before you see significant weight loss. So the whole pathophysiology makes sense to me and to me I call it medical Bariatrics fast.
Is what I call Medical Bariatrics, you get all the benefits of bariatric surgery without doing any surgery because you can get almost everything the same like obviously it's a lot more, you know, you have to do it the compliance with bariatric surgery is easier than the compliance with fasting I guess for me. I don't know I still entertain the notion that there may be more than one way to skin this cat and that I think bariatric surgery is probably a great example of putting three things in place. I've actually seen data that look at making no change to a patient other than altering the morphology of the duodenum and that improves type 2 diabetes which again if you bypass the duodenum, you would bypass what that problem is. They're so because you know, the thing with the bariatric surgery patients, is there not fasting for that long, right? They're going to have fasted for 12 to 18 hours before surgery and nowadays those patients are dripping in liquids.
That our caloric even the day of or the day after surgery so they might have a 24-hour fast but there's no question that their caloric intake is lower during that first three or four days. I remember that you've got the malabsorption to right. So the roux-en-y is both restrictive and malabsorptive. Right? That is not only do strict restrict how much they can eat the amount the eat doesn't all get absorbed and that's why I get dumping syndrome. So on I agree with you. That's a good point. It's hard to do it based on just how much they're eating. I mean technically we don't know how much they're absorbing. I like your term, right which is look let's just refer to this as medical Bariatrics and it's super potent when you have purely restrictive things like the lap band. It's like boy those things didn't work at. All. Right. We thought they'd be great lap bands purely restrictive easy to put in and so on and it's like, yeah, you look at the numbers of people and they're just dropping, you know, my friend.
Is a surgeon says yeah, you know he is to put in lots of lap and he says now the most common procedure I do is removal of lap bands because everybody wants to get rid of them because they the the pure restriction didn't work. So dripping in the drinking sodas and they're drinking milkshakes and stuff and they're not getting the malabsorptive part, which is that roux-en-y and therefore that was the problem but I agree with you. I'm not against bariatric surgery. I just think that as a sort of solution for everybody. It's a much more difficult problem because there's a lot of expenses. There's a lot of expertise as opposed to the sort of easy thing which is hey everybody can do fasting it's just a matter of spreading knowledge and making it easy, right? It's not that people can't fast. It's that people tell them they shouldn't fast right like if you go and look at Ramadan or something like that right people can fast if it's the norm or lent or Orthodox, if you look at what the norm is people can follow that is
Is that the norm is so far off? We tell our kids. Oh, hey, you got to have a snack. You got to have it. You know you have kids right? It's like after school is a snack like you get a you know the other day. I got a thing home saying oh your son is going on a trip, but don't worry. We're going to give them lots of snacks. I'm like like why why why did you need to do that? Right or you know, you send your kids to play soccer right? I do right? I did not they don't anymore. It's like somehow everybody thinks that between the haves of soccer. The parents were taking turns bringing snacks. It's like you don't need to give them juice and cookies in between halves of soccer. Just let them play the game. The game is fun. Right but it's this culture where it says You must eat all the time. The skipping breakfast is perfect example. Oh as soon as you get up, you got to start putting muffins in your mouth. Otherwise, you're gonna die, right you're going to die of heart attack. Like what the hell did you see the publication a couple of weeks ago that?
That people who skipped breakfast had a higher cardiac mortality.
Yeah, that's what I was referring to. It's like oh my
God, what's your explanation for? That study? I'm sure you've been asked about it a dozen
times because these nutritional epidemiology studies are so dangerous, right? It's because those people if you tell everybody that you have to eat breakfast, then you're going to select a group of people who don't listen to you. Right and they're going to be unhealthier there on healthier in a lot of ways. You can't measure you can measure smoking you can measure this but there's so many things that you can't measure that are going to influence why those people who Skip breakfast are more likely to have heart attacks that Association may exist, but it's not causal and that's that's the thing right? It's a correlation not a causation and it's a very dangerous assumption to say that hey you can eat breakfast and now prevent heart attacks because that's what gets out into the Press put them off in in your mouth as soon as you wake up and you'll have less heart disease. That's not what the study shows that that's the implication that always comes out.
And in the
press my issue with these studies some of yours I suppose is that there's a non healthy user bias to a lot of these. So the one of them are obvious examples of the studies that suggest the diet sodas are you know worse for you than sodas, but of course mrs. A very obvious or clear thing that you might be missing which is who are the patients who are going to disproportionately consume diet sodas, you know, certainly a subset of the might be people who are more health conscious and say well if I want a soda, I'd rather it be diet than not but it's more often the people who are being told like you can't have a regular soda. And so therefore you're selecting for Less healthy patients, that is my interpretation of that study. Now while we're on that topic do you think there are clinical benefits from a 16-8 just to use that example time restricted feeding pattern. So if you said to a patient who came in to see you, I want you to only eat between noon and 8:00 p.m. Nothing outside of that.
You don't make any other change. Do you see them get better
we do. So I think that you would do better if you fix what they eat inside that eight hours to but if you take their diet and just squish it into eight hours. I think that like we see people get better like we see people change a lot because as I said, we did sort of one meal a day where we squished it even further and those people basically they didn't even change their diet that much we talk to them about it, but we didn't focus a lot on it. And if you actually probably were to ask them. My guess is their diet and change a huge amount but just by squishing the time that you're eating your sort of forcing people away and I think part of the issue is that in the old days like in the 70s what you had was a fairly lengthy fasting period anyway, that's why you have the term breakfast, right? So you eat dinner at 6 p.m. And you eat breakfast at 8:00 a.m. It's 14 hours of fasting as your Baseline, right and that's every day without even thinking about it.
Now it's kind of spread right Sachin Panda has done all these studies of how long people actually eat and it's like, you know constantly the minute they wake up to the minute you would bet. It's almost 15 hours a day that people are eating. I think that's gotten so bad that when you squish it back to a normal sort of 16:8 sort of thing is 14 hours and 16 hours like 14 hours was sort of Baseline in the 70s and 60s just a little bit but because it's gotten so bad when you squish it back into that. We do see a lot of people who benefit just from that one intervention alone and you know to me it's always about practicalities that is is it easier. So if you have people for example, say two strategies one is counting carbs, which I think can work versus counting the number of hours that you don't eat. It's like it's so much easier to tell people between 12 and 8 as you're eating window. Everything else don't eat versus look at everything that you eat in the day try and calculate how many carbs it is and add it up so that you have some
Arbitrary less than right less than a hundred twenty less than 50 less than 20. It's so difficult whether you're counting calories or whether you're counting carbohydrates are doing macros, right? It's just so difficult to do. It's so much easier to say things like only eat between this hour and this hour and don't eat anything that came in a box kind of thing right those to me that's practical useful advice as opposed to say, let's get your carbs from 55% to 40% It's like it's so difficult. It's just and I'm not saying that it can't work. I think it can work. I just think it's so hard to implement when you're seeing patients sort of every few minutes, right? Like, how are you going to do that from a practical standpoint? Right? It's not
feasible. I completely agree. I mean, I think there is no simpler instruction than when to eat and when not to eat and yeah, I think combining these things can often be incredibly potent. I don't know I've seen mixed results on 16:8 truthfully. I've seen some patients who
Have really significant Improvement. I've seen other patients experience. No improvement whatsoever. We typically will push that window tighter 18 622 to again the tighter you push it the more benefits you see, but I've really seen no substitute for what I call intermittent fasting. We use that terminology very distinctly. We reserve the term time restricted feeding for up to 24 hours of restriction, but we use the term intermittent fasting to describe what I think that term means which is you intermittently periodically IE fast and fasting can be a complete reduction of calories or it can be a hypo caloric fast. So you can consume somewhere between 20 and 40 percent of your normal caloric requirement for a period of time typically look at three to seven days and you repeat that cycle. What type of protocols do you use for intermittent fasting?
Your patients
we use all of them. So because we're predominantly clinical will individualize. So the things we take into account is one how severe is it? So severe type 2 diabetic on a huge amount of insulin. We're going to give a more stringent schedule than somebody who's just sort of pre-diabetic and wants to sort of prevent it from getting into diabetes. So the other thing is how old they are and how willing they are to do it. So we see a lot of people who are in their 80s we have people in 80's doing like, you know, we had a lady who was like, I think you did 61 days, right and she's not young right and we have people in the 80s nothing. Yeah. That's what she said. Although sometimes when you actually go into it. Sometimes they have little things here and there but she said she did 61 we have lots of people who do long fast like that and they don't have any problems. We monitor them very closely though, but generally we don't do that. There's no point taking that much risk a lot of times. She actually just felt good on.
That's why she did it, but we don't usually push it long like that. But we will if we need to but it depends on how quickly so it's how severe is it? How old the patient is and how urgent it is because we have people who have a ton of disease, right? And we're like if you don't get this diabetes fixed, like right now you're going to be in a world of trouble. So we had this guy he's actually in his 40s. He had a non-healing diabetic foot ulcer for like a year followed by a plastic surgeon. So he actually came into the hospital and I saw him because I was seeing him for his diabetic foot infection gave him antibiotics. I said, you know, your problem is not your foot. Your problem is your diabetes, right? Because you know, the reason you have this foot ulcer is because of diabetes, you don't get foot ulcers. If you're not diabetic right unless you have severe PVD or something, right? But the point is that if it's not diabetes, which is causing your foot ulcer. You gotta get rid of your diabetes. I talked to his dad. I guess this guy was like in his forties and the dad was Greek Orthodox, so it's
That was like oh, yeah. Yeah, let's do this. So so we put them on and we put them in Fairly strict restriction we started from I think on a week of fasting and then 36 hours three times a week and that ulcer healed like within three weeks. It was like ridiculous how quick that thing just healed up
you led with a single week of fasting before cycling 36 hours weekly or did you lead with the 36 hours
I started with the seven days and then we did like 36 hours because it is severe. Honestly, he was going to get his foot chopped off at some point.
You're definitely more aggressive than I am because you're seeing much sicker patients. I never lead off with water only fasting for patients. Usually what we do is we go we push the windows of time restriction, which as I said, I'm going to go I'm not convinced there's huge benefit and time restriction. I think there's some benefit. I think the biggest benefit of time restricted feeding is the psychological one. It's breaking the cycle you just described earlier, which is
People think intravenous access to food is essential for life. If they go more than two hours without a meal the sky is going to fall and so in many ways time restricted feeding is just a way to prove to them that that is total nonsense.
I actually think that the long fast do exactly the same thing.
Well, yes. Yes. Yes, but you can't you can't lead why me at least for me. I haven't tried leading off with that talk me through like that particular patient. So first of all, let's Grant it that he now has agreed to try this. This is a patient who is not entering a fast the way I would enter a fast which is I usually spend a week in ketosis before the fast which means I'm showing up in a fast with a ketone level of somewhere between 0.5 and 1 millimolar of beta-hydroxybutyrate. I sail generally pretty easily into these fasts not all the time. This is a guy who's got a respiratory quotient of one. He is a completely obligate glycogen consumer. He's probably not
Devised a fatty acid since Guns and Roses were popular. This is a guy who's going to be in for a world of hurt when you strip food away from him because within a few hours he's going to sense. His liver will sense glycogen levels are low. It's time to eat. So how are you getting him through that?
There's no easy way. We just tell them this is like gonna sock for a week because you're not going to feel that grade. You're going to be hungry and all this sort of stuff. It was the urgency and I'll tell you that people actually can do it, you know quite a lot of people have we've done it on a number of people and most of the people as long as you warned them ahead of time that it's going to be tough they get through it. But the thing is that the psychological if you've done a week, you know, that 24 hours is like nothing and you get into ketosis so fast because that's the fastest way to get into ketosis right? It's just too fast. There's no faster way you can do it than that, so it's not easy but
Is reasons why and that's why I say it's important that everything is individualized because I'd never do this to somebody who's like 40 and has an A1C of like 650. It's like why put yourself through that right? Do it gradually. You have no time restrictions. This is a guy who's actually coming into the hospital with diabetic foot ulcers that were getting close to osteomyelitis. Right? It's like it's a much different situation than not right? I'm trying to make sure that somebody doesn't wind up. He doesn't wind up getting a bad infection in somebody wind up chopping his foot off which is why I was super aggressive in that case. I've heard stories of other people have put patients on starting sure to attend a fast and so on so they don't all do well they don't all get through it but it's an option. That's all I'll say and I hate to be prescriptive like, oh you have to do this you have to do this and this is what seeing patients does to you. I find that the people who are super dogmatic are the people who never see patients.
Yeah. I can't agree with you more.
Because patients always prove you wrong. You think your stuff works. Well, like 40% of your patients. It doesn't work in right? So then I'm like I'm never like oh you have to do this you have to do this because it's like yeah, I know it doesn't work, like like carb restriction like some people it really does work. Well and some people it really doesn't work that well and the study show the same thing right Chris Gardner study. If you look at this play between low-fat and low-carb some people do great on a low-fat diet and some people do terribly on a low-fat diet. It's the same diet same with the low carb in general the low-carb people do better. But when you look at the individual differences, that's why people get on get on Twitter and and they start talking about. Oh, it's all about this or it's all this all this then I'd like I know you don't treat people because if you actually treated people you'd never say stuff like that you'd never get on somebody about taking the opposite position because you've been proven wrong soul mates like every day. I'm
Wrong like something doesn't work. And that's why I'm always like let's do this. See if it works. If it doesn't work, we're gonna adjust it. And then if it works better than we're going to keep doing that and we'll adjust it. Right and that's that's where the kind of art of medicine comes in so you can start but to me, I always tell people like there's two options when you do fasting you it's like going into a pool you can wait in or you can cannonballing right and both are acceptable one's a big shock to the system but it works and the other is not as big a shock and it still work for this particular patient. You know, that was one of the few few times because most of the time it's not that urgent that I did recommend. You just gotta do this and his father was on board and he was on board and we monitored him super closely. We actually started him in hospital because he happened to be in hospital anyway, so I put him on clear fluids, right and then just told him don't take anything with sugar just just water and and he did very very well and I've done it to a few other people with diabetic foot ulcers as well because I consider that one of the
The more difficult like that's that's something that you really have to take care of and I always think that basic foot ulcers to me is fascinating because it's like if you think about this overflow Paradigm, it's like why diabetics get these infections that nobody else gets. Why do you get mucormycosis? Why do you osteomyelitis? Why do you have diabetic foot ulcers? You don't get like foot ulcers from ischemic cardiomyopathy foot ulcer, right? You don't get that ischemic cardiomyopathy mucormycosis. It's like it's because what you're doing is you're putting all this sugar into the body. Then when the blood glucose goes up you give them insulin to really Jam that sugar into the body right in the body takes it your liver gets all this sugar and start sending it all over the place pretty soon. Your whole body is so full of sugar that everything just starts rotting and that's why you get the kidney disease as I get the eye disease and that's why the bugs just love it because there's so much sugar and nutrients everywhere so they get in
Foot and they never go away those foot ulcers never heal. You get these weird infections that you never see anywhere else you get thee, you know, the rashes the in can't though sis and all. Ah, it's just you got way too much sugar. It's all about the whole body sugar and not just the blood sugar. That's the real shift in thinking and Paradigm that to me makes a lot of sense. And as soon as we're able to empty out all that sort of sugar and I always use the analogy of a sugar bowl. We're just filling up the Sugar Bowl. You got to empty that sugar bowl and then the sugar won't spill out and that's why it works and the fasting is the same thing. So we'll individualize it. So based on all those sort of factors like including what they want to do, right? You got to talk to people and say what are you willing to do? Right and a lot of people aren't willing to do a long fast, but a lot of people are actually it's striking
what percentage of your patients are willing to do a water-only fast for at least a period of three
days right off the bat because we offer this as a treatment to everybody.
Don't say okay. Well, if you've never heard of it will still recommend it and like 50% right off. The bat won't do it any fasting at all right there. So like ingrained and I had this discussion yesterday with a fellow. I told him. Oh he needs to fast. He was he's developing, you know prone area and he was going into renal failure. And I said really you need to fast and he says my endocrinologist says I can't fast no way so it's like okay, that's it right there. So 50% of people won't fast for any period of time at all, like not even like five hours, right? So it's changing I think views on fasting are changing, but you can see like, you know, did you read that whole thing with Jack Dorsey he gets on CNBC or whatever and everybody goes like
Crazy that oh, he doesn't eat for 24 hours. It's like what's the big deal? Like? Why do you think we carry body fat? Right and it's like look, he's looking good. He feels good. What's the big deal? Why are you getting on them? Right but the idea is so ingrained that we have to eat have to eat have to eat even to lose weight. We have to eat that they won't do it. So if you take away the 50% who won't do it right off the bat. Then you have people who will do it for short periods of time and probably only about 20% might agree to like a longer fast mostly and it's not the physical side that actually got some it's always the psychological side. The physical stuff is super easy to deal with it's the psychological part that's really hard. That is when you're looking at somebody who's eating and you're trying to fast. It's like really hard right? And yeah, you can do it once in a while. But if you do it sort of breakfast lunch dinner breakfast lunch. That's the hard part and that's where we focus a lot of our attention working on the psychological how to
Your environment up for success and coming up with different strategies for success and creating a supportive Community that's going to help your success. That's the hard part because think about religions like Ramadan. How do they all fast? Because people say, oh I could never fast. It's like but you know that literally hundreds of millions of Muslims fast. It's like it's because the environment is supportive if all your friends are doing it and all your family. It's it's not fun, but it's not that difficult to actually do it and that's the difference and now we're recommending it for people who have no community and that's what we trying to create community of people who are accepting and also that's part of the point of bringing it into the mainstream. I wrote a couple of books about this of course, and that's the point if I wrote a couple of articles that I sent to jam our something to get pure reviewed. First of all, the pure review would kill it and then second of all you'd get no traction whatsoever and then you're not doing
Anybody any good because by making it sort of more out there you make it more acceptable for people to talk about it and to accept it as a viable treatment.
So let's go through some of that stuff so that lets say that that 40 year old Patient First of all appreciates the severity of what you've shared with him and his dad which is look it's one thing to have diabetes which you do but you're actually in quite a late stage of this if you're I mean, I don't remember the literature on this but from my days in surgical training The Five-Year mortality, once you have an amputation with type 2 diabetes is staggering. So I don't remember what it was but it was so high that the point was once you're getting a toe amputated or foot amputated or something like that. The probability you're going to be alive in five years is incredibly low so I could be wrong on this but I feel like the The Five-Year mortality was something like 70% So if you're in your 40s and you're already getting a diabetic ulcer that's not healing there's a nonzero chance. There's actually a significant chance.
Not going to make it to your 50th birthday. So he says I'm in you mentioned something that I think can't be overstated which is you have to be in a supportive environment. So if a patient tries to fast and they are surrounded by people both their friends and family and also there are other medical practitioners who are telling them. This is a horrible idea. Well, that's a recipe for failure. So now let's posit that we've also got the support of the medical team and the friends and family. What are some of the other tricks and trades. I mean one of the things that I hear a lot about is Peter my sleep is really hard when I'm fasting. How do you address that?
That's a tough one? Because they all can't sleep. There's not that much to do. We tell them one to expect it. So it's one of the things is that if they know about it ahead of time then they're much more accepting. So we say look you may not have a lot of trouble going to sleep because people get so people don't understand but the whole sympathetic nervous
System and everything is revved up, right noradrenaline. All that stuff gets revved up and a lot of people actually can't sleep and I said, well, you know, what if you find that then you know, stay up do some work and so on and and don't worry about it, right? This is a temporary situation. It's not going to last forever. We just want to make sure that everything gets better and that patient. I don't think he had any sleep trouble but we did warn him. So we one of the things we do is we warned them ahead of time of all the potential problems. So it's like the book what to expect when expecting right? So it's not like it makes the symptoms any better but it makes dealing with it a lot better. So we tell them hey look you can have headaches those will go away. You can have cramps. This is what to do. You can have diarrhea. This is what to do. You can have constipation. This is what to do sleep is, you know, you can expect this and you need to watch this in terms of your blood sugars and and so on and this is what to do with your medications and that patient. We actually I think his last anyone see that we saw was like five point nine, which here is actually classified as non diabetics.
Not even pre diabetic. So we took them from a couple of medications and a non-healing diabetic ulcer to non-diabetic like within a couple of months. Yeah. I took a little bit longer than somebody else and everybody responds differently and even a couple years later. He's like non-diabetic, right? So it's like that was the whole point we missed, you know, in medicine. It's so difficult because we're so ingrained into these patterns of thinking that is you have a obesity which causes type 2 diabetes which causes a foot ulcer. So we get the plastic surgeon to the bride deal sir. It's like that's the least important part you need to get rid of the diabetes and get rid of the Obesity and then he will actually get better. So warning people ahead of time is one thing that we do and it doesn't make the problem any better but it makes them deal with it one day they trust you because they go. Oh, hey, I got a headache for three days and then it went away so that
They know you know what you're doing and that gives them confidence and then just having that support so he had his father of course who is going? Yes. Yes. Yes you need to do this. And that was that came from his religion. So it was a good setup for that many times will actually get the opposite which is what you're saying is that I'll get that patient. I'll say this is what you need to do. The family says, oh man, that's crazy and the family doctor says, oh man, that's crazy and the endocrinologist as you must never do this that nothing changes, right they have this and so
on my tip on this one Jason is that in anticipation of that sympathetic outflow. We recommend that patients take phosphatidyl serine with the fast in the evening and that sort of calms down the adrenal glands and then even just an oral over-the-counter Gabba. Unfortunately, it's becoming harder to get centrally penetrating Gaba over the counter, but even just peripheral Gaba will sort of take
Down some of that sympathetic tone. So that coupled with some other sort of sleep supplements actually not only tends to help people sleep at a number of people note that you can have some of the best sleep imaginable with those lower levels of glucose higher levels of ketones. Now, what about electrolytes? How do you manage the electrolytes and particular sodium and magnesium during these longer fasts?
There's nothing specifically we do actually so we monitor it very closely of course magnesium is the one so everybody worries about sodium and you can get some people who do get a bit sodium depleted. But if you're otherwise healthy your kidneys should never get to that state because there are people from the inter salt study their people that actually barely eat any salt at all and still survive fine. So your body should be able to reabsorb all the sodium. It needs magnesium is a bit more difficult because a lot of type 2 diabetics are depleted of magnesium to start so we'll often recommend magnesium supplements, and that's where a lot of the cramps and so on just Kickin some
People do get a little dizzy and so on. So that's when we use the bone broth, which is technically not a fast but it's like got calories and you know amino acids and stuff. But that's where we'll use bone broth. For example where you can put a decent amount of salt in and take it and and still feel. Well. We monitor the electrolytes more just because we want to make sure that nobody's getting into trouble but I'll tell you that the number of times that I've actually had to intervene or tell somebody to stop the fast because of electrolytes is like zero, I think I don't think I've ever had a case where the blood work came back and said, oh my God, they have to stop there are some other things like if they get diarrhea, for example, it can be fairly significant then then that might play a role but you know when they get those we tell them stop and we are always like, you know, we're always super cautious because we monitor them very closely. These are relatively sick patients, right? So they generally have a lot of medical issues, but we monitor them very closely. We give them very careful and
Options that hey if you don't feel well you need to stop right away don't even tell me stop it and then tell me right because the point is that you can let's figure out what's going on. Then if it's a solvable problem, then we can do it starting tomorrow or we can do a totally different regiment shorter fast more frequently. We're not stuck to this one thing or we can do ketogenic diets, or we can do something else, right? There's all kinds of things that we can do without doing a long fast and some people actually hate the long fast and some people actually love the long fast. So we always say don't get so rigid in your thinking that you have to push through like the one thing we tell people more than like don't just push through because that's when you're going to get yourself into trouble. There's always tomorrow to start another fast if we figure out what's going on with
this don't you find it's helpful to explain what you're pushing through. I mean, for example, even if I fast for seven days, there is no day.
During that seven when I am not at least at one point quite
hungry. Oh, yeah the hunger for sure. We always say you can be hungry but make sure you're not like lethargic or
something. I think it's important for patients to understand even seasoned faster still get hungry. But what I find interesting in my wife who doesn't fast but is sort of interested in like why I do it. She can't believe it right. She can't believe that you know, I'll work long hard days and exercise and do all that stuff while fasting and she's like, aren't you just starving and I said truthfully. Yes every single day. I feel quite hungry at some point in the day, but it's never more hungry than on a regular day. If I'm getting really hungry like being hungry on the seventh day of a fast is not a more profound hunger. It's the anticipation of that that becomes problematic which really speaks to the Shakespeare quote about nothing is either good or bad but thinking simply makes it so the anticipation of that hunger seems to be a bigger problem maybe for your patience. It's less of a concern because the highest
Is the amelioration of the diabetes but do you spend much time thinking about how they can minimize muscle mass loss with the obvious loss of protein intake or do you just say look it's so intermittent that that we do this fasting that we're going to take whatever we have to take in the most catabolic sense and then deal with on the back end or do you do anything specifically with respect to
exercise nothing specifically because again, I'm treating different population like I'm not treating bodybuilders, right? I'm treating 65 year old women for them. It's like they don't even know how much muscle mass they have and honestly, I'm not even sure like there's some protein loss and I'm not sure that's a bad thing. I mean, I think that most people actually don't get a lot of muscle loss like you can get protein loss which is connective tissue and skin and this is one of the things that people always rag on me about but at this is clinical medicine, right? So I've treated thousands of people with fasting and some have lost a lot of weight like hundreds of pounds and I've documented
You case studies in my blog and stuff and one of the things that's very unusual about fasting for weight loss A supposed to weight loss for other things is that we don't see the skin problems because skin is protein like it's not fat right skin connective tissue its protein and you do go when you do the intermittent fasting you do go through that period where you have gluconeogenesis and you're breaking down Protein. That's the whole point of Atop A G for example is breaking down protein. It's not fat and I'm not sure that it's bad thing. So we actually get much less. I've never referred a patient for skin-removal surgery and some people have lost like a hundred and fifty pounds for like years, right and and they actually don't notice the problem a couple of my colleagues who I work with and they've noticed the same thing that you don't have as many of the problems that you do with regular sort of weight loss, which is chronic calorie restriction where you get these big flaps of skin that you have to go in surgically and take out the question is why doesn't your body get rid of them because it's super
Plus your body shouldn't be keeping it around your body should be getting rid of it. And it doesn't because you never went through this period where you're undergoing gluconeogenesis where you actually are breaking down protein. So do you get more muscle loss? There's a been a couple of studies on Alternate daily fasting which really haven't shown increased muscle loss or lean loss. I think that the protein loss is often confused and called muscle loss to me. It makes no sense. Like your body has a system and I'm not talking to situation where you have 4% body fat, right? I'm talking about a situation where you have 30% or more body fat. It makes no sense that the body should store food energy as glycogen and body fat but the minute you need to use it. You start burning muscle do we think our bodies are really just that stupid that they're going to do that. It's like storing firewood for the winter then as soon as you need to use it you chop up your
Sofa and throw it in the fire like who would do that, but we think that our bodies are just that stupid. Like I don't think their bodies are that stupid. I think that there's a period which is fairly limited during the fasting where you have gluconeogenesis. Then you can see fat oxidation goes way up, right and Kevin Hall. I think that some of these studies on what happens and Cahill, of course did all those studies, you know on what happens during actual starvation. He got to remember that he was no wimp, right? These are like 60 days of fasting right not like 16 hours. It was huge and these people were not even overweight it was you know, there are some studies that you just think. Wow. How did they get away with that
was before the days of the IRB.
There's a great study. I don't know. If you've seen this there's two studies where they took people we're not even overweight. They fasted them for 60 days and gave him a big slug of insulin. It's like why it's like just to see what would happen.
Well, no. No, I mean that study was to actually see if the ketones were protective in the presence of hypoglycemia. They injected those patients with insulin took their glucose down to below 1 millimolar these people to walk around with it. Yeah, they did totally fine provided. They had enough BHP. That's an
incredible. This is incredible, but you'd never get that study done today. You get thrown out like you'd get laughed at right by the IRB like you're gonna drop people's glucose to less than 1 like are you serious? Everybody now thinks if you don't eat for 24 hours, you can get seizures, right? But the point is that yes, it was for the ketones and stuff. But there's a great study like it's stuff that you just couldn't do these days but the amount of protein so when you look at all the Cahill studies all the classic studies of fasting the the relatively limited period that you're actually burning you've got the gluconeogenesis in your burning protein, which I actually think is a beneficial thing in the right situation where you are have somebody with obesity and so on and and if you look at studies like not all
Did a bunch of these studies and he tried to estimate how much excess protein somebody who is overweight has like 20 to 50% more protein than a regular person. There's more skin. There's more muscle. There's no more connective tissue. There's blood vessels. There's all kinds of extra protein that goes along with being overweight and that all needs to go if you're going to if you're going to do it, so I'm not actually I'm not actually wear it like so again, I've treated a few thousands of patients with type 2 diabetes. Remember, I'm not talking about the guy who has 4% body fat and is a bodybuilder and can tell how much muscle he has based on how much he lives. I'm talking about the 65 year old person with a lot of body fat and generally excess protein in that case. The question is how many patients have I had to stop because I was worried about muscle loss. That would be like zero right in six years. And because I use it in a therapeutic manner. That is I'm not treating one.
Personal weeks right thing right? It's like every person who comes in every 10 minutes. I'll say this is what you need to do this wishing to so it's just part of my clinical practice. So it's like hundreds of patients a year and over six years. It's like thousands of patients like 0 people had to stop because I was worried about muscle loss, right? So it's like, okay tell me how that is going to be a big concern to me. Right? And this is where again it's like people who don't fast and people rag on me all the time about this right as like, oh what about this would but there's some like, okay how many thousands of patients have you done this for? Try it on several thousand patients and then come back to me and tell me if muscle loss is the most important thing for this 65 year old 300-pound man on a hundred and fifty units of insulin.
It's a totally different situation last question because I know you've got to get back to the clinic we've taken you away from it. Do you think there's a role for this type of fasting and people who are actually healthy but looking to get
Benefit that goes beyond getting rid of a disease. They don't have in other words. If you take a person who's not hyperinsulinemic IE insulin sensitive by these definitions though. We made a pretty good case that everybody's insulin sensitive without a weapon dystrophy, but you take a non obese non-diabetic non nafld the insulin sensitive non hyperinsulinemic individual who's asking the question will periodic fasts reduce my odds of chronic disease down the line. How do you feel about
that? Absolutely. Yes, because look the point of fasting is the lower insulin levels, right? So if you fast and you're healthy and you're not hyperinsulinemic, well you do periodic fast and it doesn't have to be a long time or you know, even that frequent right? So if you look at the 70s, right typical person is eating three meals a day 14 hours of fasting every day and then once a year maybe on Yom, Kippur or a during Lent or during Ramadan.
A little bit longer fast, but there are times. He's eating a lot to write Christmas and all this starts time. So that's just the balance right? It's all about balance. Like this is the whole point is that you have to balance periods where you have going to take a lot of food like Christmas, you're eating you're eating you're eating you're eating now you want to balance that with like lent where you're just not going to eat a lot because that's what they told you to do. So this is what's going to happen is that you're going to drop your insulin levels periodically, which will prevent you right? It's going to clear out all that Sugar every once in a while and then prevent you from getting diseases of hyperinsulinemia. So if you drop your insulin every so often you're going to prevent yourself or lower your chance of getting diseases of hyperinsulinemia, which are heart disease stroke cancer. Alzheimer's disease type 2 diabetes obesity. Well, that's the major risk of our current population. So you want to lower your risk of getting those gray like you're not going to lower your risk of
Pneumonia, like you're going to lower your risk of these diseases of hyperinsulinemia. So for a healthy person. Yes, I think fasting is very beneficial, but you don't have to do five days of fasting every month or something like that, right? You could do a little bit longer fasting once in a while and maybe not do some bedtime snacks and stuff.
But you don't buy the argument then that for example valter Longo Z FM D, which is a type of intermittent fast. I know you know what it is, but you know, listener might not so you know, this is one of literally a hundred different ways you could fast but he would suggest that based on a certain set of macronutrients you're consuming about thousand calories followed by 750 calories for four days. And that's what that gives you a five day cycle and he talks about doing that quarterly and would argue that there are actual longevity benefits even in the non-diabetic or not metabolically ill person again, I think for some people that sounds really extreme personally. I don't think it's that extreme.
Team in your patients that doesn't seem extreme.
It's actually fairly routine for for a lot of people that we talk to but again, it's a different patient population for healthy people. I think that they're like the data is just not there. So prevention of Alzheimer's prevention of cancer treatment of autoimmune diseases, for example of altars talking about sometimes I don't think that there's enough data to say yes or no, like could it work? Absolutely. It could work. I actually think that there's good reason to think that these things will work to prevent a lot of those diseases like not necessarily so of course to me all the diseases of excess of growth and hyperinsulinemia to me are clearly are going to reduce your risk, but now you're talking about other diseases like autoimmune diseases and I think that there's good reason to think why they might work but is there data to show it? Not really?
Yeah. This gets back to the first point of will we ever have evidence-based guidelines to support this?
It's impossible not improbable. And therefore we are stuck thinking about this through mechanistic
lens. Yeah, but see the thing is that again people have it all wrong because people say, okay so say they're talking about a five-day fast once a quarter or something like that whether you do fasting mimicking or regular fasting, let's say somebody says you should do five days of fasting once a quarter or once a year. Okay. So the evidence-based medicine people are always way off because they say there is no evidence to suggest that five days of fasting once a year is beneficial. They're right, but they're completely wrong from a clinical perspective because there's also no evidence that five days of fasting a year and a person whose normal weight and otherwise healthy is harmful to you. So now you have to say what is the risk of doing that five days of fasting so five days. So in a year, you will eat three meals a day one year you'll eat thousand meals for five days. You're going to make 15 meals out of it.
Thousand that's it. That's the extent of what you're doing. What is the risk of that? I'll tell you it's just about zero like yeah, you're going to be hungry and stuff. But if you're otherwise healthy the risk is very very very low and then you say what is the benefit? Well, there's not really any great evidence of benefit either. But because your risk is so low your risk to reward ratio is pretty reasonable. Why wouldn't you do it? That's the question because the risk is so low. Maybe there's no benefit. Maybe there is a benefit. I can't tell you right and it is the same for all drugs, you know that there's a certain number needed to treat so number needed to treat a 50 means that 49 out of 50 people simply do not benefit from that drug that you gave them and it's going to be the same for fasting. There's going to be one person who benefits and fifty people who don't benefit but the risk to reward because when you give a drug the risk starts getting so high that the risk the reward ratios, they don't make sense, but for something like fasting missing 15,
Meals out of a thousand. Yeah, it can make sense and that's why you know, all these sort of ebm. Zealots are all like, oh, there's no evidence. There's no evidence. It's like you don't need evidence. It's assessing the risk and the reward and what clinically makes sense to me if I had for example some kind of autoimmune disease. So let's take this disease rheumatoid arthritis that there's no evidence that fasting is going to do anything for and dr. Longo says, well, you know, you can reset your immune system. If you do seven days of fasting, what would I do? I would absolutely do it as opposed to taking a bunch of toxic drugs like prednisone. Like you've seen what prednisone does to people why wouldn't I do seven days of fasting the risk of that is zero say I don't get any benefit from that not then I don't have to do it ever again. But what happens if things get a lot better, I've just treated my own disease. The reward can be so high, but you don't have to guess at it. You can just do it.
Give risk. There's some in my opinion kind of weak epidemiology suggesting that skipping breakfast will increase your risk of gallstones. How often are you seeing that in your
practice? A lot of people have gall stone so I don't see an increase risk, but on the other hand it's going to be tough because the problem is that people who follow a low fat diet, of course their gallbladder, you don't need by. Alright, you need file to emulsify the fat. So therefore you're all tired just sits around with all this stuff and you get sludge and so on. So I think the low-fat diet can certainly predispose you to Stones. Then you start eating a higher fat diet and then it's squeezing out and you're getting Stones. I don't see it clinically as a problem. I think what caused a lot of problems was probably the lower fat diet because you're simply not getting the flow enter a hepatic flow like the bile supposed to come out. It's not supposed to sit there. But when you get rid of all the fat it just sits there that's is the balance our body makes it sticks it in the gallbladder so that when you eat fat you can squirt a little bit of a doubt
Now we think we're so much smarter than our body which has survived for millions of years that we're going to eat zero fat and just have all this stuff this sludge just sit in the gallbladder because you never took it out. Like how does that make sense to me? It makes no
sense. Well on that note. We are at exactly the time when I know you need to get back to clinic. So I want to thank you greatly for your insights both at the what I would say are hugely Paradigm challenging level, especially as it pertains to insulin resistance and hyperinsulinemia, and then also at the boots on the ground clinical level. I know that very few people have the experience treating patients with fasting protocols for type 2 diabetes, and I think you're doing fantastic work. So thank you very much for
them. Thank you.
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