Insulin resistance and why we get sick with Prof. Ben Bikman — Diet Doctor Podcast

[Music] welcome back to the diet doctor podcast i'm your host dr brett sure today i'm very pleased to be joined once again by professor ben bickman now um if you've heard of ben bichmann hopefully you have we did an episode with him uh podcast episode number 35 and i got to be honest he's just a great guy i really like speaking with ben talking to him getting his opinion on things and hearing his res about it all the research and i think um i i try not to be too much of a uh was it a boy fan or something or just a fan of his because um i want to push him and i and i want to make him clarify things because he's so good at answering questions and so good at being clear about what we know and what we don't and still talking with passion and having the experience of being a researcher doing the studies and therefore knowing how to interpret studies so we spent a lot of time talking about insulin resistance and hyperinsulinemia um because that's what he's been focusing on i mean so to get to his uh sort of his accolades he's a phd in bioenergetics and did a postdoc in metabolic disorders he is an associate professor at byu in the department of physiology and developmental biology and he focuses on insulin and ketones and their role in type 2 diabetes and obesity and metabolic disease and neurodegenerative disease so this is his area he knows more about this area than just about anybody in the world at this point i would venture to say he's also been very busy trying to reach people with his message so he recently wrote a book why we get sick as you as you'll hear he's involved in two companies health code and insulin iq which he talks a little bit about at the end of the episode so uh very busy guy a great guy a very smart guy who really states things appropriately in terms of what we know what we do and states it with passion so i hope you um oh and humility i mean he's such a humble guy as well um so okay i'll stop going on and on about how great ben is and instead just let you get to the interview here with professor ben bickman [Applause] [Music] well my good friend professor ben bickman it's a pleasure to have you back to the diet doctor podcast once again thanks for joining us oh brett uh the pleasure is mine it's great to see a friend and talk all things metabolism absolutely well we were joking before we got on online that you're every time i interview you your your biography is getting bigger and bigger which just shows you've been a very busy and productive man so it's good to see because look when there's we have to be honest there's so much information out there coming from different sources and different people but if i figure if you want to know about insulin resistance and metabolic health you want to know about the guy who's got the phd who's doing the research who's teaching the subjects and who who probably knows more about the subject than most people in the world and i got to figure at this point that that's you i mean and not to put you in an uncomfortable spot yeah no i am glad i i'm glad to be looked at as an authority uh because i do think my sentiments do depart from others who who um speak about insulin resistance and and act as an authority and i don't mean that in a derogatory way but claim and authority in the realm of insulin resistance and so i think i'm glad to be a dissenting voice in some instances uh with regards to insulin resistance its causes its consequences for example yeah interesting that you say a dissenting voice and i guess there it depends on which sort of camp you're talking about right and it's sad that we even have to have camps when it comes to science because science should be science but there is sort of a disconnect between maybe what the the the traditional or current medical community feels about insulin and insulin resistance and what some of the science says so is that is that what you would sort of say is where you're a dissenting view compared to the medical community or did you have something else in mind yeah yeah well i am certainly a bit of a misfit in that regard uh you know and for example that's highlighted in my view of type 2 diabetes where conventional medicine looks at type 2 diabetes as a glucose disease and i vehemently disagree with that sentiment and say we need to look at it as an insulin disease but even within the low carb community there is some debate as to what are some of the fundamental causes of insulin resistance and and so in that sense i uh i guess neither of you is dissenting because there shouldn't be a uh you know in science there shouldn't really ever be a static consensus and so i i shouldn't invoke that term um too lightly but i would say my views don't align with others who speak in the um in the low-carb space about insulin resistance and so i'm happy to have my voice be one of them that people will hear to add to the conversation all right well we we we hit the ground running right away talking about insulin resistance so let's rewind for just a second and tell us how do you define insulin resistance yep yep this is an important point to start with because i think it helps really clarify where some people may see things differently so to me insulin resistance as a term derives from the original observations from cell specific studies so to invoke the term insulin resistance is really invoking the perspective of the cell and some cells like muscle cells for example or maybe the very earliest and even fat cells these are cells that manifest with insulin resistance in an isolated cell culture we can we can expose the cells to different situations that actually make them insulin resistant they're not responding to insulin very well so that's half of the definition as insulin resistance is used in a in a whole body situation or a clinical situation then the other half is very relevant though and it's sometimes missed in the definition because insulin resistance in a human will always always always be accompanied by hyperinsulinemia that is the other half of the coin that cannot be dismissed it cannot be overlooked or tossed out if we are coming up with a working clinical definition of insulin resistance so again insulin resistance is defined as some cells not responding to insulin and hyperinsulinemia those are the two sides of the coin and they we have to understand both of them to understand why insulin resistance is so relevant to virtually every chronic disease yeah now that's a really interesting point so it's not the cell's not listening to insulin but not all cells are the same right so if you talk about insulin resistance in the muscle cell versus the fat cell versus the liver so tell us some of the nuances there about how maybe you can have insulin resistance from one cell but not another yeah yeah that's exactly right there is very much a cell specific phenomenon here where like you listed some that are known to become outright insulin resistance or or very strongly insulin resistant and that and the muscle is a great example um when the muscle becomes insulin resistant virtually all of insulin effects are compromised including its um inhibition of proteolysis or inhibition of protein breakdown its inhibition of glycogen breakdown within the muscle and its stimulation of glucose uptake all of those things become compromised in the muscle cell however there are other cells and an an interesting example would be the theca cells of the ovaries that do not become insulin resistant and so here we have a cell that in the context of the whole body is suffering because of the hyperinsulinemia which is kind of both cause and consequence of the insulin resistance but here the insulin is acting with all of the sensitivity that it ever did and because the insulin resistant body is the hyperinsulinemic body now we have a thickest cell that is over stimulated with insulin and that leads to polycystic ovary syndrome because insulin inhibits aromatase it inhibits the conversion of testosterone into the estrogens and and of course it's a little known fact that all estrogens were once testosterone in males and females it's just the gonads make that conversion through aromatase insulin always inhibits aromatase always but because we have low levels of insulin in a healthy situation the inhibition of aromatase and thus the inhibition of converting testosterone to estrogens is always very mild but now in the case of the hyperinsulinemia we've taken that inhibition of aromatase to a whole other level and now we're inhibiting the production of estrogens too much and now she doesn't have the estrogen peak with the menstrual cycle and thus we do not have a follicle that actually ovulates and so she doesn't ovulate and the ovaries just get they maintain all the follicles which become cysts and now she has a cyst loaded ovary or ovaries so we uh i i highlight this just to highlight two very different cells that are each responding to this overall insulin resistant slash hyperinsulinemic state and even within brett it even gets more complicated because we could look at say the endothelial cells the cells that line the blood vessels and normally insulin will stimulate a mild degree of growth a little bit of hypertrophy in the endothelial cells and it will stimulate the production of nitric oxide which allows vasodilation which lowers blood pressure but in the case of insulin resistance and hyperinsulinemia we have the hypertrophy still happening but now it's happening too much insulin is still stimulating hypertrophy of the endothelial cells narrowing the blood vessel but unfortunately the insulin-induced production of nitric oxide is compromised that cell that specific biochemical event is insulin resistant and so now we have less nitric oxide production and the blood vessel that once would have dilated when it saw insulin stays constricted those together combined with a few other variables explain why insulin resistance is so pivotal to hypertension yeah so those are a couple great examples of how it really is hard to just say insulin resistance and and i think it applies to every cell but at the same time it does help simplify things because there is sort of this common thread that it's maybe the insulin resistance in like the muscle cell and the liver cell that triggers the cascade that then affects how different cells are are affected because pcos is thought to be a condition of insulin resistance but what you just said it really is a condition of hyperinsulinemia too much insulin while still being sensitive to insulin so i think that's a very important differentiation that we don't hear a lot about yeah and bret there's there's one other um point to this that i think is so important especially in with people that are familiar to the general low carb community um i i do believe that the term insulin resistance is invoked incorrectly where people are saying that adherence to a low-carb diet is causing physiological insulin resistance i disagree with that conclusion quite strongly because you cannot have insulin resistance without hyperinsulinemia in the body truly i'm unaware of any instance of actual insulin resistance without hyperinsulinemia and so that term people are using the term physiological insulin resistance incorrectly that that is a real thing physiological insulin resistance is real but in both instances which is puberty and pregnancy you still have hyperinsulinemia in both of those states important okay hey time out for a second yeah you've got two you've got you've got too much knowledge and you love to talk about things and i don't know too fast that's on my list of things to talk about but you know now that i'm thinking about it i think we just need to take a step back and say look what is insulin what does insulin do because um i think most people have an idea of insulin and certainly in the medical community insulin regulates blood sugar but it's got so many other functions that when we talk about hyperinsulinemia and insulin resistance that are so important and you already alluded to some uh in the blood vessel about how it's not insulin doesn't just regulate blood sugar but it can affect uh the hypertrophy of the of the vessel wall and production of nitric oxide so we're gonna get into the physiologic insulin resistance and all the other downstream effects of hyperinsulinemia but tell us some of the basic functions of insulin that we're going to need to know about as we discuss its contributions to other disease processes yeah yeah good good yes so so for better or for worse and maybe more for worse in conventional medicine insulin is generally just viewed by nature of its actions on glucose so glucose is it goes up when someone eats a starchy sugary meal and hyperglycemia is dangerous um that's that's a even very rapidly dangerous situation given its effects on the kidneys and so think heavens the body has a mechanism for very rapidly lowering that glucose level preventing it from being dangerously high for too long and insulin is part of that in fact much of that and much of that is insulin effects on the muscles eighty percent of glucose after someone eats a meal that has carbohydrates eighty percent of that glucose will go into the muscle and almost all of that will be given the actions of of insulin so again for better for worse insulin is typically viewed through the lens of its effects on glucose and its glucose lowering effects however insulin has i i i say that insulin basically controls fuel use in the body so whether the body is at its simplest storing energy or using energy whether it's more inclined to store or whether it's more inclined to use and even waste energy insulin controls which which with direction the human metabolism is leaning storage or spending and and so that's that's more reflective i think more accurate um at almost every cell insulin will tell the cell what to do with energy and and the theme of it is take in nutrients and store them build something from these nutrients or you know a more complex way to store the energy or nothing having to do with energy at all telling it to make proteins for example or make lipids that will be used in non-energetic processes but say for structure or hormones yes so it's it's really a growth hormone in a way i mean it's it's telling cells to grow and that can be fat cells to grow but it can also be you said protein it affects proteins so can it also trigger muscle cells to grow so i mean we think of insulin as like you know nowadays you know there's so much talk about insulin as being bad the effects of insulin are bad but it's got some vital functions in our body for blood sugar regulation like you said and for for regular human growth but like a lot of things in modern society uh you know good intentions you can say are sort of led astray by our lifestyles and that's when you get in this concept of of too much insulin so um now a big part of the message is that insulin isn't just involved in type 2 diabetes but also has downstream effects on high blood pressure cardiovascular disease cancer neurodegenerative disease so what is sort of the common thread that insulin has in its function that can lead to all these other diseases yeah yeah so i i think the only common thread we could approach is insulin telling cells what to do with energy ultimately and whether to grow or or or or not um in the case of so across each cell i i would think that's probably as close as i could get to creating a common definition and in the case of say like if we highlighted some of the pathologies you just mentioned in the case of cognitive decline that is thought to be the loss of insulin functioning at the brain is thought to be part of the loss of glucose uptake which is a very real quantifiable event in humans we can detect that in in cognitive decline whether it's mild cognitive impairment or outright alzheimer's disease we can detect actual reductions in brain glucose uptake and brain glucose metabolism and insulin does mediate some of the brain's glucose uptake it has uh in the the brain has insulin dependent glucose transporters now it has an insulin independent transporter as well but we know that the fact that it has glute4 and insulin dependent glucose transporter does suggest strongly that insulin is relevant to at least some of the brain's glucose uptake so that could be part of the pathology um with with the cognitive decline or the neurodegeneration and another example would be say fatty liver disease where insulin appears to be pivotable pivotal and that is insulin resistance in the global sense because it's not the insulin resistance per se at the hepatocytes that are causing them to store fat it's the hyperinsulinemia the other side of the coin so so once again you know highlighting the fact that when we talk about insulin resistance in the context of health and disease we need to understand that that is a loaded term that encompasses the hyperinsulinemia which is not discussed and indeed when i'm mentioning hyperinsulin resistance i am putting the two together in one term yeah yeah you know i think it was so interesting in your book how you mentioned that even textbooks from i think 20 years ago listed the brain as an organ that had no response to insulin and absolutely insulin had zero effect on the brain and now that's completely false and it just it's that old that old saying that 50 percent of what we believe is false we just don't know what 50 yeah well that that turned out to be one of them and and so now it's opened up this whole new field of neurodegenerative diseases possibly being insulin and glucose related and when it comes to diseases like that though i also want to say or ask you you know what is the level of evidence that in your opinion that we have linking high insulin levels as being a causative factor in a number of these disease states is it associated is it causative you know where do we stand now and where do you think we're headed from that standpoint yeah that's a great point to make and and i would want anyone to know lest i be accused of of kind of having a one-track mind i am not i'm not attempting to say that insulin resistance is the only variable say for example causing alzheimer's disease i would never be so bold as to say that but so in humans there's strong correlational evidence which is probably about as good as we can get with humans that we find that insulin resistance is one of the strongest predictors of alzheimer's over a 10 or 11 year period and there was one very specific study that the the title starts with something like insulin predicts alzheimer's disease over 11 years so in humans there's strong correlation in fact one study from finland found that fasting insulin had a higher statistical significance to alzheimer's risk than age did and so it's a it's a very now by that i mean the p value was stronger um with insulin than age so pretty pretty compelling in rodent models we know that if we start manipulating the insulin receptor or the glute4 glucose transporter we cause neurodegeneration we start to cause cognitive decline in the animals so there's a much more causal link which is the reason we use animals at all it's to do it's to do causal mechanistic research that we just can't do in humans now adding to that my lab we have this in the second round of review right now specific to alzheimer's disease where we study gene expression from human brains so of course postmortem people who died without any evidence of alzheimer's disease and people who died with conf well as confirmed as we can with alzheimer's disease and we did a wide genome analysis and found that there were fundamental reductions in almost every gene involved in glucose uptake and glucose metabolism in in the dimen in the brains with dementia now i cannot say that that's a result of insulin resistance and i wouldn't try but i would say there's it lends more evidence to this kind of energetic deficiency of alzheimer's at the origin of the disease but interestingly when we looked at genes involved in ketone uptake and ketone metabolism we there was no significant differences across either the brains with dementia or the healthy brains interesting very interesting well so so that that i think that's a very good um overview of sort of where we stand for insulin resistance and dementia so would you say the level of evidence is similar for hypertension and for obesity and for cancer or do we have sort of like different uh or some sort of you know more proven than others yeah yeah i think so i i think so insofar as you can in a human situation um you can with type 2 diabetes well well we know in humans that if you cause insulin resistance um insulin stimulated glucose uptake is compromised so i think in the case of type 2 diabetes we can say that the mechanism has been established in humans um in the case of um what was the other disorders you mentioned hypertension hypertension yep yep yep very well established hypertension as as a consequence of insulin resistance has been really well documented from the 1980s with gerald reven's group so that's a much more established causal relationship to the point that um they often will say that if it's uh primary or essential hypertension it's generally going to be uh actually a result of insulin resistance so yeah with with alzheimer's it's probably uh more we're relying on animal data to establish causality with other disorders like hypertension and type 2 diabetes we have more much more causal evidence even in humans yeah and i think it is so interesting that that hyperinsulinemia and insulin resistance um are correlated and potentially causative of so many different diseases which originally sort of at least me as a physician the way i was trained and thought was that they were all sort of separate you know alzheimer's is very different from heart disease and high blood pressure which is different from diabetes which is different from cancer but really there can be sort of a an underlying unifying mechanism that at least makes them more likely to happen but yet here's the disconnect between having the evidence to say that's the case and the medical community sort of accepting that so uh you know in your assessment you know you're not a physician which probably gives you an advantage in this setting um why do you think there's a disconnect there yeah yeah i i what an excellent point and in fact brett one of my um it's an interesting thing to be the the phd biomedical scientist you know claiming to have insight into clinical practice when i have actually no experience in the clinic um and and my hope you know but kind of as an answer to this question in all humility the advantage that the phd has is that the phd scientist gets paid to ask questions and to find answers to questions the md or do physician does not get paid to be curious and to ask questions that the md and do gets paid to see patients that is the mechanism of compensation and so you know i get paid to be curious so i can just kick my feet up look out the window and ask well how does insulin resistance cause hypertension and i can go in and find the you know the five distinct mechanisms that explains this connection but but it's not fair for me to say well an md you should know this you know i'd be talking to my doctor my physician friends and say well of course you should know this no they shouldn't because that's not their job they don't get paid to be curious and i don't mean that in a derogatory way the mechanism is simply you get paid to see patients so the hospital would say see your patients and if the physician were to say you know what i'm going to take an hour off right now and just do some pubmed searches and find some answers to some biomedical questions that's not going to get them very far and so i think the disconnect to answer the question is maybe in fact it's reflected in what you said earlier where where there's there's not there are knowledge gaps i don't remember exactly what you said 50 of what we think we know will be found to be irrelevant or outright wrong in you know in a few years from now and and i think that there i think it's happening i i think that there is a growing awareness and this is my central thesis of the book and even my my professional out my professional goals it is to help people understand that they're to varying degrees not 100 probably in any situation to varying degrees insulin resistance is a fundamental part of most chronic diseases and the sooner we acknowledge its role the sooner we can detect it as a problem and and perhaps as a causal problem to whatever the disorder is we have in mind and the better we can treat it and that is most explicitly evidenced in type 2 diabetes which isn't surprising because that's the disease that is most explicitly a consequence of insulin resistance but our our ongoing obsession with glucose means that over the years of the patient's life their insulin is climbing climbing climbing reflective of the insulin resistance but it's enough to keep the glucose in check and so because conventional medicine is only looking at the glucose in the context of metabolic health the hyperinsulinemia is missed and that it in it is only 10 or 20 years later when the body's become so resistant to its own insulin that now the glucose is climbing and then we detect the problem so if we shift the paradigm away from glucose on to insulin we first of all detect the problem sooner because we can detect the elevated insulin much much sooner before the glucose starts to climb and then second by looking at the insulin we did we that we treat the problem better especially in the context of type 2 diabetes the patient would come in they've had years of hyperinsulinemia and now they have hyperglycemia and the patient the the typical physician might say all right well we just need to lower that glucose by any means even to the point of pushing the insulin up even higher because there's no regard for the insulin there's no respect insulin is like rodney dangerfield it gets no respect and so we push the insulin up even higher and it works it lowers the glucose but a meta-analysis published just a few years ago that evaluated all available data on insulin treated type 2 diabetics found no evidence of improvements in any clinical outcome in fact they found evidence for adverse events and and what tends to happen in fact we know the more insulin we're giving the type 2 diabetic they when we give them insulin their risk of dying from heart disease triples and their risk of cancer mortality doubles and they typically gain about 10 to 20 pounds within just the first six months and so when we put a type 2 diabetic on insulin therapy pushing their already hyperinsulinemic state to super physiological insulin we kill them faster and make them fatter but but brett there's so much unfortunately there's tricky language that is used to describe type 2 diabetes because people will say despite the hyperinsulinemia once they start to see the glucose climbing the wording is clever they will say insulin becomes deficient or insufficient and that's a relative term because it never becomes it never goes to zero never i mean if it does that's type 1 diabetes and so it's the wrong problem so insulin over the course of the person's life in type 2 diabetes it will start normal it will go very high and then in some type 2 diabetics it will come down a bit but it's still multiples higher than it was before and so the wording is is dangerously ignorant or deliberate would they say insulin is insufficient it is to keep the glucose in check even though they have a lot there isn't enough to keep glucose they're so insulin resistant they can't keep the glucose in check so then the physician is justified they feel in pushing the insulin up even higher again making them fatter and sicker because it's not a glucose disease because even though they have normal glucose levels once we put them on insulin therapy we're killing them faster it's because it's a disease of too much insulin and that paradigm shift is essential to truly understand type 2 diabetes and to varying degrees the same thing applies for other disorders like polycystic ovarian syndrome or alzheimer's or fatty liver disease and so on well that was a a very passionate and strong statement about the role of insulin and type 2 diabetes and i think that's such an important point you made though the way the wording is used is so important because it totally changes your mindset and the framework and i mean look let's be honest insulin is life-saving if your blood sugar is too high insulin can be life-saving but it kind of goes on this concept well if some is good more must be even better or like if if you know if we can use a little bit then why can't we use a lot and it was i mean for a long time it was kind of unknown that these higher levels of insulin were harmful and it was thought that it was just because well your risk of hypoglycemia is higher but it wasn't the thought that just having the too much insulin stick around for so long itself was harmful and i think that's where the tide is sort of shifting and where your sort of impassioned message is really important um but so i i wanted to just get to maybe a little bit of the details about type 2 diabetes because there's also this concept of beta cell failure where the beta cells in the pancreas are some people call it burnt out diabetes where now the the the pancreas can't keep up with the insulin production um and so that's where the words of it being insufficient are but isn't there a point where the where the pancreas literally can't put out enough insulin um even to match sort of normal physiologic levels for people who you know even if their blood sugar was under good control or are you saying that does doesn't happen yeah well yeah this is i i i want to be cautious here because i think i know the sum of all evidence but i'm a humble scientist so my to my knowledge and if it's actually type 2 diabetes not an autoimmune destruction of the beta cells namely type 1 the beta cells are never gone in a type 2 and in fact there is instances to show that as insulin production might have dropped in type 2 diabetes there's beta cell reversal with type 2 diabetes as the person incorporates dietary changes such as fasting for example beta cell they note what they call beta cell reversal in fact that's how some of the manuscript titles um that's some of the terms used in these manuscript titles this reversal of beta cell loss so it is not this irreversible destruction of beta cells like we have in true type 1 diabetes it might be a reduction in insulin production where it starts to slope back down but to my knowledge it has never gone we've never started this to wage war on the beta cells insulin production might have gone down and and i don't know the reasons for that uh but i would say that's fine um lower your glucose load coming into the body so that that that lower level of insulin production is now more than sufficient to meet the the glucose load coming in and and so i i can't speak to the reasons why in fact i'm not sure anyone can why is insulin coming down why is it sloping downwards in some not all in some type 2 diabetics which is amplifying or accelerating the hyperglycemia i don't know why i would say it does not get to zero not even close it stays higher than it was before and and so if that's a problem it's only a problem insofar as the person is continuing to probably demand a high insulin load by consuming starches and sugars right so here now we get to sort of the cause of insulin resistance and hyperinsulinemia so is it too simplistic just to say sugar sugar's the cause carbohydrates are the cause i mean because that's what a lot you'll see online now you know there's part truth in that and or maybe oversimplification so tell us about that yeah yeah so that's a great question and and i'm glad to share my insight into this because it might not align with with others in the low-carb space i believe that there are primary and secondary causes of insulin resistance and it is not as simple as just carbohydrate consumption and people want will want to invoke the catavins and say well these are people who ate um high high carbohydrate diet and had no instance of of insulin resistance and type 2 diabetes i think that's true i think that's accurate that's fair to note it's also i think accurate to note that um we don't eat carbohydrates the same way um more more sort of ancestral diet cultures did you know if we were all only getting our carbohydrates from tuberous um vegetables i don't think it would be a problem you know even even if we're getting our carbohydrates from from just baked potatoes i don't think that's going to cause insulin resistance in an otherwise healthy person so i i wouldn't want someone to think i'm claiming it's that simple but of the primary causes i call these primary because if i'm actually growing because there's evidence to show that in isolated cell cultures the three causes i'll mention in a moment will directly cause insulin resistance and also in human studies even not to mention rodent studies all three of these will directly cause insulin resistance rapidly and so i'll maybe i'll mention them in sort of reverse inverse relevance so the first one would be perhaps stress where we know that cortisol and the catecholamines are insulin antagonists and so if cortisol is elevated over a long term including artificial cortisol like through prednisone or dexamethasone these cortisol analogs to control inflammation um which will be my next point but but these these cortisol if cortisol is elevated the body will become insulin resistant rapidly and we see this in humans we see this in animals and in cells so there's it's just reflective of the insulin antagonistic actions of the stress hormones and this can be from something even as seemingly benign as sleep deprivation which causes an acute cortisol spike which is likely part of the reason why the insulin the body's insulin resistant the following day so it's very acute phenomenon the next cause is inflammation and and we see this in autoimmune diseases and in and in acute illnesses and infections the body becomes insulin resistant when inflammation is up and we can we can introduce pro-inflammatory cytokines into people through infusions and into rodents and sure enough we cause insulin resistance immediately and then the last one is one that some don't agree with but the evidence is simply too overwhelming including some from my own lab which is hyperinsulinemia itself chronic and this is where carbohydrates would come into play the chronic consumption and frequent consumption of high loads of refined starches and sugars which would basically ensure that a person has elevated insulin every waking moment of the day and so hyperinsulinemia itself is a cause of insulin resistance this can be done in isolated cell cultures and in human and rodent models so even at physiological levels as has been done in human levels in human studies it's not like pushing their insulin up to super physiological doses is all that is what you have to do it doesn't have to be that extreme so those are the three what i consider primary and then the third or the fourth rather i call it a secondary not to diminish its relevance but because i think it's more of a of a multi-multi-cell phenomenon overall in the whole body and that is the excessive consumption of linoleic acid as i outlined this in the book but linoleic acid is is one the most commonly consumed fat in the human diet now um which which ancestrally it never was uh although we always ate some amounts of it because it exists in natural fats as well but now that we get most of our fat from soybean oil and and corn oil and canola oil we're getting uh much much higher i mean thousands of times more of this fat than we ever did in human history and linoleic acid makes fat cells insulin resistant by forcing hypertrophic growth rather than hyperplastic growth and so so i am getting into the weeds a little bit here um but but i suffice it to say that as linoleic acid is altering the growth of fat cells making them insulin resistant that insulin resistance spills into other cells subsequently now i don't know i've i can say that in muscle cells when i even even fat cells in an acute term if i incubate them with linoleic acid they do not become insulin resistant as acutely as the primary causes or what i'm calling the primary causes but so i'm making some assumptions here that i can that i don't need to make with the primary causes we know that linoleic acid affects the growth of fat cells in a way that would make them insulin resistant and when fat cells become insulin resistant i consider it the first domino to fall yeah well i think that's really interesting and i like how you um are sort of careful about how strongly you say that and how you label it as secondary rather than primary because there is sort of a difference in the in the level of association there and you know it and we have to admit in in humans doing any type of nutritional study and trying to l and trying to boil it down to one food group or one type of of food is so hard because we don't eat one type of food we eat a diet and we eat a certain amount of calories and the effect something may have in a a hypocaloric diet versus a caloric excess diet may be totally different how that one macronutrient or that one specific type of fat affects you um whereas in a cell culture though totally different because there you have complete control and i think that's that's really something that's nice about what you bring to this picture because you you do have knowledge of both sides of the story both the sort of the nutritional epidemiology and the the the studies that you do and and therefore can even better interpret so i think that was that's well said um now you did mention about evolution um and about how we ate in evolution and and i want to touch on that but also briefly touch on what you call your plagues of prosperity which is a term i've heard you used before which i really enjoy because again it comes down to um you know the the hyperinsulinemia the insulin resistance it may have to do with what we eat but it also has to do with how much and when and how much we move our bodies and how our sleep is and how our stresses and the things you mentioned as the causes so so i assume when you talk about the plague of prosperity it's not just food right it's like the entire life lifestyle oh yeah i think so yeah so my i do love alliteration so the plagues of prosperity was just my attempt to sound clever and yet and yet try to be accurate which was which was me my attempt to highlight um the relevance of our modern environment and its role in causing diseases that our ancestors would have had no concerns with now cancer is a more sort of primordial disease that i think has always happened but things like heart disease and diabetes and alzheimer's disease the rate at which we're seeing these i think is safe to say it's unheard of in human history and and so yeah i i do think i consider the biggest problem to be the type and frequency of food of eating the type of foods we're eating and the frequency with which we're eating them and namely that these are foods that are high carbohydrate and high fat and that is not something that happens much in nature in fact to my knowledge the only real source of foods that would have been high carb and high fat would have been breast milk it's not something that we get much of or or mammalian milk other than that carbohydrates is really its own class of food and and and rather other foods come protein and fat together yeah i think that is a great point about so many things in modern society have changed and one of the biggest one is that combination of carbs and fat and and so when it comes to um sort of the etiology of insulin resistance a lot of the the science that has been done showed that it's an uh increased accumulation of fat within the muscle cells um an increased accumulation specifically they say of saturated fat within the cells which leads many to then conclude okay well eating fat must therefore cause insulin resistance um so how does that play into what you just said about the combination of carbs and fat and yep i love that you're bringing this up um partly because i've actually explicitly published papers on the effects of saturated and unsaturated fats on insulin resistance and so it's something i can speak to with a you know a fair degree of authority so fat it depends on the fat um whether it's relevant or not so for example if a muscle is taking in saturated fat and it's using that to turn it into triglycerides that is totally inert so triglycerides have no effect on muscle insulin sensitivity and we see this very well it's very well confirmed and and thus and refuted the idea that triglycerides are contributing to insulin resistance even if the triglycerides are made up of saturated fats as part of their fats but however there is some truth to this idea that that fat is contributing to insulin resistance and once again it depends on the type and by that or now i guess it's the appropriate time to mention a molecule called ceramides where ceramides are a type of fat that a cell will make in response to inflammation in response to cortisol and in response to chronically elevated insulin and it will take it will take a saturated fat palmitate which is the most abundant saturated fat even if we're eating zero fat palmitate the saturated fat palmitate will still be the most abundant fat in the blood because of the lipid the liver producing palmitate when insulin is high the liver is in its production of palmitate will be the main contributor to the saturated fat in the blood so regardless the the cell will even the muscle cell it will take a palmitate molecule and it will take an amino acid and it will start to create ceramides and ceramides are known disruptors to the insulin cascade to the biochemical events that are mediating the insulin pathway and so when people are citing or or mentioning that the reason and many many plant-based advocates will do this they'll say well saturated fat causes insulin resistance and and so that's a reason to avoid any sources of saturated fat and i hear that and think that is a person who has taken an ounce of the truth um including some of what indeed what i have published myself finding that saturated fat is necessary for the backbone of ceramides but they then confuse the issue by claiming that it's the dietary saturated fat that's necessary in that event when in reality someone can be eating no dietary saturated fat and still be producing ceramides from the saturated fat that the liver is pumping out very readily from glucose and insulin yeah and then there are also studies showing that if you measure blood levels of saturated fats it doesn't necessarily correlate with the saturated fats you're actually eating so along those same lines right so that's exactly right yeah and i think that gets back to the point also of what i i mentioned earlier about how you know the number of calories you eat and the like you were saying the combination of carbs and fat that completes com that creates a whole different atmosphere that may or may not make it more likely for fat to get deposited in the cells and trigger insulin resistance so it goes far beyond just one type of food which i think is so important and then okay but now now let's get into this concept of physiologic insulin resistance because when when someone eats low carb and we're going to get into ways to combat insulin resistance in a little bit but one of those it happens to be eating low carb so people claim that when you are eating low carb you do have some signs of insulin resistance physiologically but that is a good thing because it's physiologic insulin resistance and not associated with the elevated insulin levels but now i think you may it sounds like you've got some issues with that at least the definitions of it so i'd love to hear your take on it yeah i do i do um i i think that the the glucose intolerance that's the term i want to use uh the glucose intolerance that is manifest in long-term adherence to a low-carb diet doesn't fit any description of insulin resistance um night there is neither actual insulin resistance at the muscle and there is there is also no hyperinsulinemia and me mentioning this is based on well the first observation that insulin goes exquisitely low in someone who's adhering to a low carb diet so we knock off the hyperinsulinemia immediately but someone could then return and say yeah but still there there now you just gone to the fundamental insulin resistance at the muscle cells which is why the long-term low-carb adherent eats the bagel now and now their glucose stays higher goes higher than it did before they ever went low-carb but that's not true and george cahill decades decades ago found this phenomenon where he was fasting people for for days you know weeks and that is low carb you know i mean that's fasting and we would they are very much ketogenic very much in ketosis and when they injected them with insulin these human patients with insulin their glucose dropped immediately they had an immediate and exquisite response to the insulin suggesting that this long-term ketogenic state was not causing any insulin resistance so i think by any definition the body is not becoming insulin resistant in response to adaptation to a low-carb diet i do however think what we see is is is for lack of a better term uh a reverse or an inverse metabolic inflexibility and let me now you probably already know where i'm going with this uh but in in typical metabolic inflexibility or let me even start more basic a healthy person is metabolically flexible where they eat a mixed macronutrient meal and they go into sugar burning mode you know blood sugar blood glucose and then they fast for a few hours later and they shift over to relying more on fat for fuel so that's a metabolic flexibility people with insulin resistance because of the chronically elevated insulin are stuck in sugar burning mode even when they're fasting so it's been hours or a day later and they're still burning more glucose than you would have seen in the healthy person who would have shifted to fat burning so it's like they're stuck in glucose burning mode unable to burn the the fat as as well as a primary fuel long-term adherence to low-carb diet i believe puts us in the reverse situation it causes this reverse metabolic inflexibility where the person has shifted so strongly to fat burning that now when we load the system with glucose we have a bit of a delayed glucose burning and i cannot speak to the mechanism so i would want i mean it doesn't change the reality that we do see that they are compromised and shifting back to glucose so i think it's fair to to create this term of reverse metabolic and flexibility but i cannot speak to the mechanism i don't know why it would be happening because we know that they are exquisitely sensitive to insulin when you give them an insulin load and we've done this in animal models um where they've been adhering to a low-carb diet give them an insulin load and their their glucose drops they're very very insulin sensitive so i i don't think it's fair to mention insulin resistance in any way um i think it's more accurate to either say that they have a glucose intolerance an acute glucose intolerance or reverse metabolic and flexibility um and a lot of this is probably just semantics or people may be hearing me and they say well that's what i meant when i said insulin resistance but that's just that is um if so then then it's too inaccurate we we cannot be mentioning insulin resistance when when the two fundamentals of the insulin resistance coin are non-existent in long-term adherence to a low-carb diet yeah i think that's a good point because then you're saying the solution sounds a lot like the problem which which can get really confusing when you're still using that term insulin resistance so i think that's a good point to eliminate that even if we're talking about the same thing and there's you know there's some theory that it was it's an evolutionarily beneficial thing to have this glucose intolerance adaptive glucose sparing you know whatever you want to call it that some people are both physiological yeah because um if your body if your muscles are using fatty acids um then you're you know you want to save the glucose for your brain so you don't want your muscles to be burning the glucose so they're resistant to glucose not resistant to the insulin i guess you could say yep yeah so so it's like a lot of things it's a potentially beneficial adaptive um mechanism for our ancestors that our modern lifestyle has turned into a detriment and contributed a lot of chronic diseases yeah well said so now that we've laid the groundwork for you know how pervasive a problem this is and how significant of a problem it is you you said um i want to get the quote right how we live can both be the culprit and the cure for insulin resistance so it's it's you know not all grim we can do something about this and it's actually probably not all that complicated to do something about it and one of the first things you talk about in your book is exercise and the importance of exercise and we hear time and time again now that you can't um you can't outrun a bad diet and you know exercise by itself isn't the best thing for weight loss but could exercise by itself be a major contributor to healing hyperinsulinemia and insulin resistance oh yeah i think it could i i do think that the person would be still ignoring what i would contend as the more relevant variable but no question no question the advantage of exercise that that cycling of contraction and relaxation will start pulling in glucose independent of insulin so you can take a profoundly insulin resistant you know uh quadriceps and you start contracting it and it will engage those glucose transporters that will pull in glucose that normally insulin must be present to engage but independent of insulin and so it creates an immediate mechanism to lower the glucose um following the exercise and thereby allowing the insulin to come down and the moment the insulin comes down insulin sensitivity starts to improve so yeah yeah i i'm a huge advocate of exercise there's no question it can have a direct effect on improving insulin resistance however just to highlight the relevance of diet not to diminish the exercise because that was the point of this bit of the conversation there's a study that found that when you finish exercise and i mentioned this in the book if you finish an exercise session with a carbohydrate-rich meal you undo the insulin sensitizing effect of the exercise so and that's tragic because most people will go to the gym they get done the gym and then they go get a smoothie or they go get they drink a bottle of gatorade or they because they're told they're told well you're you're training for a marathon you got to eat all these carbs to train for the marathon and they they might be able to finish the marathon but paradoxically they've gained weight during the course of training for it and that shouldn't be happening yeah i can't tell you how many workouts in the in the 80s and 90s training for triathlons i finished by by smoothie when you said it it just like uh i did that and you have this concept that you're doing something so good for yourself um so i i definitely want to get into nutrition because it's such a big part but exercise i like how you covered exercise in the book especially when you said friends don't let friends skip leg days that was great but so this concept of resistance training because if you people want sort of the minimum effective dose right if i only have limited amount of time where am i going to get the biggest bang for the buck um in the book you made the case for resistance training but for a lot of people you know they don't know how to get started maybe with resistance training or the concept of exercise to failure what does that mean what does that feel like how do i do it so what kind of advice would you give somebody about the the best exercise and the best method of exercise to combat insulin resistance yeah yeah that's great you you mentioning the minimum effective dose what that is the perfect way to describe it um how can we maximize the benefit uh i i would say in answering this question i would say that my sentiment on what is the best exercise really is the one you'll do so if someone hears us talking about doing resistance exercise and this kind of over uh this this older lady is thinking i'm not going to do that and so i may as well not do anything no if your exercise is going to be going on a walk then go out on a walk but insofar as a person is willing and able to incorporate some resistance it could be something as simple as sitting in and out of a chair just while you're watching a show you're watching a show in the evening just sit up get up and out of your chair repeatedly just keep going until the muscles are uncomfortable if a person is comfortable getting down on the ground just do even knee push-ups even not even doing push-ups but just holding a position until it starts to get hard and the muscles start to burn that is a good enough starting point because if we can give that stimulus to the muscle that we are doing something hard and we need you to grow the bigger the muscles get the more easily we are disposing of glucose and clearing it from the blood helping lower glucose helping lower insulin and we're addressing the problem yeah i think that's a great point that this this sort of vision of of pumping big iron in a gym can be uh can be a definite detriment to people because they think i can't do that so why get started so it was a great example but but then again you hear this term like exercise to failure that sort of like that's what you need to do when a lot of people maybe don't understand what that even means mm-hmm yeah so that was me so when i mentioned in my in my my answer a moment ago just kind of go until the muscles are burning yeah in some people that would be failure um and and that would be at least the first version of what failure would look like like oh that was burning my muscles are getting uncomfortable that might be enough for the first several days and then eventually when i say going to failure it's this idea that now you're doing those chair squats until you just can't get back up you know you you kind of went down and you're trying to get back up and that was the end of it and so you know and that would look the same in push-ups you're doing those knee push-ups on the floor during commercial breaks or something you've done them until you're pushing pushing you can't do another one ah you flop to the ground that's what failure would be when you cannot repeat the activity again and that's just that's a tough that's a mentally exhausting way to work out and so i do mean what i said a moment ago where a person doesn't start with that they start until they go to the point where it's just a little uncomfortable the next day they go a little further a little further and before they know it um at any age they find that they can go to failure and that's when you really will start to get more substantial muscle gains yeah yeah i think that's great and also in the book you you really emphasize compound movements and move and using the larger muscle groups and i think that's important it's it's sort of its own topic of how to best exercise for insulin resistance but you you cover it very well but like you alluded to if you just talk about exercise you're probably ignoring the bigger factor which is nutrition and again it would be easy to say look low carb and keto diets are very good diets for reversing insulin resistance that is i think true and very well proven in the literature but is it the only way yeah yeah excellent it is certainly not the only way um in even someone it a little pains me to say this because i think the diet is incompatible with human survival but someone could even go on a plant-based vegan diet and if what i'll say is anything that departs from the typical standard american diet is going to improve insulin resistance and that is why we do have human evidence to suggest if you take people and put them onto a kind of low-fat plant-based diet their insulin resistance will get better absolutely there are studies out there to confirm that independent of monitoring any macronutrients intermittent fasting has been shown conclusively to also improve insulin resistance so that's one that is totally undisconnected from any kind of macronutrient manipulation you don't even have to worry about your macros you're just fasting for these periods of time but then what i think what led me to be more of an advocate of a low-carb diet when it comes to insulin resistance is the studies that compared directly the low-fat diet that if you take a person on a standard american diet put them on a low-fat diet it gets better true enough but what happens when you compare the low-fat diet with the low-carb diet the low-carb diet will outperform the low-fat diet and and that that to me was the eye-opening realization year it's a handful of years ago when i was my my view on insulin resistance was clarifying and to the point that i was more acknowledging the role of insulin itself as a cause of insulin resistance in indeed as a result partly of my own experiments in my own lab my my evolution then became well all right if i'm finding that insulin is part of the cause of insulin resistance what is the best way to lower insulin and and of course it's that's an easy step you say well it's cutting the car cutting the one macronutrient or controlling the one macronutrient it actually elicits a substantial insulin spike and that is carbohydrates and indeed like i mentioned a moment ago it bears out it plays out this way in the clinical studies to my knowledge of all the dozens of studies that have put humans onto a low-fat diet or a low-carb diet not one has ever shown a a significant improvement in the low-fat diet beyond low-carb not one and in contrast there are dozens that have shown significant benefits beyond the low-fat diet from the low-carb diet so there's a clear winner there uh in my mind uh and it should well the evidence i shouldn't say in my mind i shouldn't qualify like that the evidence is clear a low carb diet will outperform a low-fat diet but but again to be diplomatic and scientifically objective there are numerous interventions that will improve insulin resistance when a person is starting from a baseline of the standard american diet yeah i think i think that's very well said summarizes the literature and is open and honest about the different ways to do it and then so each person has to find their path that is going to be most sustainable for them most enjoyable for them um that is also going to that is also going to impact the insulin resistance and if you talk head-to-head if if the low-carb diet is so much better than the low-fat diet but you love a low-fat plant-based diet and that's the diet you're going to stick to okay you're probably going to do better off than that than you otherwise would have following a standard american diet and then there are still other things you can do like we talked about with exercise and then like you talked about with the the plagues of prosperity and the the sleep and the stress focusing on these things so i mean do we have pretty good science to back up by giving attention to your stress paying attention to your sleep and improving those will independently improve insulin resistance as well no no i i've not seen any study that has ever done that so we only we only have the inverse showing that sleep deprivation and stress is causing insulin resistance but taking someone who's insulin resistant and then the intervention is improving their sleep does that improve the insulin resistance independent of any other variable i've never seen that paper if it's out there yeah and that's interesting but it's also the the what's the harm right what's the harm of of paying attention to your stress and paying attention your sleep it's only going to have other proven potential benefits from blood pressure and anxiety and depression and and other other downstream effects so it's one of those things you probably should do anyway and it's likely going to affect insulin resistance as well agreed yep yeah so at one point you also had mentioned fasting and time-restricted eating which is another really interesting topic that we're sort of i think on the threshold of just an explosion of scientific evidence of what's going to come for this um but again it kind of comes back to that question of what is the minimal effective dose which i've got you know i know we don't know the answer to proven scientifically but i really want to get sort of your opinion what you think where you think that threshold is for fasting or time-restricted eating that's really going to make a difference that is worth spending the time because when we talk about look you know trying to focus on your sleep is a good thing because it's going to make you feel better and it's it's got positive outcomes fasting let's be honest fasting is not always that much fun especially if you're talking about a three four five day fast so where is that where is that bar for you that you think people should should aim for yeah yeah that's what a great question i would i think firstly it doesn't appear there are there it appears that there are multiple good right ways to do it and i say that because if i recall in one of jason fung's recently published papers looking at intermittent fasting these case studies he published i think the patients were using multiple forms of intermittent fasting including like a five days eating two days fasting one day eating one day fasting so i think i believe if i'm remembering that study correctly and they found significant dramatic improvements in insulin sensitivity in type 2 in people with type 2 diabetes that they were using multiple strategies so i don't know that there's any one strategy that is necessarily much better than another so that once again might be of a an answer of find the one that works for you but the minimum effective dose i i can only speculate and i would speculate that i i think there's probably something around that 15 to 18 hour window where insulin has come down and now the person's getting into ketosis and i i don't say that because of the ketones that the person needs to be getting ketones in their blood i say that because i think that represents a shift in fuel use that if if someone has been fasting for around 15 to 18 hours or so then they're likely getting into the first sort of hints of ketosis and that is that itself is reflective of this energetic shift where we've shifted from sugar burning into fat burning which itself is a function of insulin having lowered because insulin dictates which fuel is being used so i i'm speculating a little and so there might be some wisdom to the 18 6 which is a pretty common um time-restricted eating protocol but but as someone gets closer and closer to one meal a day fasting my fear starts to grow that during that eating window they're going bonkers and and in that in in some people that version of time restricted eating where it's like a one meal a day or just a few hours in a day i and i say this because i've seen it happen where it basically turns into a time restricted binge purge cycle where they start to eat in that window and they go like i said they go bonkers they stuff themselves with these terrible foods and they're eating all of this right before they're going to bed and now they sleep terribly their body temperature is higher their glucose is higher they're digesting the food they're uncomfortable they sleep terrible they regret it they have remorse and they say i'm going to do it again and i'm going to do it better tomorrow and so they fast through breakfast they fast through lunch in this sort of punitive um response to the binge the night before and they do it all over again and so my i think it's it's so important i think intermittent fasting is very effective but the person must have a plan with how they end the fast they need to have it very well structured and very disciplined to to not let it become a binge purge cycle in sort of a glorified version of an eating disorder uh so so the meal how a person ends a fast is probably more important or at least as important um as how long they're fasting wow so well said so well said yeah because i i've seen it time and time again too even with two meals a day if someone was eating 1500 calories and three meals a day they go to two meals a day and the psychology of it all of a sudden they're eating 2200 calories in those two meals and then and you're not doing yourself any favors and you you're describing an even more extreme example of that and so well said that a plan you have to have a plan of how you're going to fast and break the fast and i think that's a great way to just sort of wrap it up because it really does show the way just the way i just really enjoyed talking to you because you're so passionate you're so intelligent but you're also very measured and you see things from different perspectives and you want to be clear about what we know and what we don't and that's why i think your voice is such an important voice to listen to um and why i think your book is is a fantastic book for that that same reason um and and so this is my way again of saying thank you for coming on and thank you for all you're doing and since your biography has been growing and you've had um you're involved in so many different things now where can people turn because you have so much more knowledge so much more information that i want people to be able to learn from where can they learn more from you and hear more about you yeah well brett hey seriously thanks again what a fun opportunity to reconnect now that we can't go to in-person conferences these days i don't get to see my my buddies in the in the community so it's great to connect with you um i am moderately involved in social media uh and and i would want people to know at the outset it's never pictures of me doing things it's not my when i first got on social media about four years ago it was simply to overcome the inherent hurdle in research where i would make a cool finding i publish it in a paper and no one ever reads the paper it just sort of slips into irrelevance it's the curse of of the of the scientists so i got involved in social media simply and totally as a vehicle to to share um metabolic insight uh and some of which i highlight in the book and so of course you mentioned the book anyone who's curious about it go get a copy uh anywhere books are sold that's why we get sick but but social media i'm mostly involved on instagram these days and my handle there is ben bickman phd i'm still somewhat active on on twitter but i find that i'm sort of retreating from twitter more and more as it's just becoming a very different place in sort of uh not not a place i care to to be too often these days so um also i um i'm involved with a low-carb coaching platform called insulin iq and we've developed a very good program online this is simply just a coaching platform anyone curious about this if you find like you need help in fact we're partnering with diet doctor to help give content here but they can learn more at insuliniq.com and and we have fun live sessions each week where we talk about research and and answer questions and then i'm also involved in the development of a low-carb shake so as anyone knows once you go low-carb one of the beauties of that is that you're forced to eat more real food because there aren't a lot of convenient low carb options that that are well built so this was an effort for me to uh if only for my own sake make low carb a little more convenient and that was the development of a low carb high fat high protein shake and it's i think it's the best out there anyone who wants to learn more i don't want to i won't elaborate more here go to get health and health is spelled spelled hlth gethealth.com to learn more and i provide blog posts there and eventually some video content as well so that's how to connect with me and i i love connection guys come find me on social media ask me questions it's a fun way to connect with people in a very genuine um sort of uh transfer of information if i know something that someone deems beneficial i'm happy to share it wonderful wonderful well i highly recommend people look you up and all you're doing and uh thank you again for all your work and your contribution and thank you for your voice my pleasure thanks again brett [Music] [Music] [Music] you

Channel: Diet Doctor

Views: 78,909

Rating: 4.9293346 out of 5

Keywords: keto, low carb, diet doctor, insulin, insulin resistance, metabolism, metabolic health, diabetes, chronic diseases, metabolic disease, hyperinsulinemia, saturated fat, vegetarian, vegan, exercise, fatigue, exercise to failure

Id: AhRCX3nNhA4

Length: 71min 53sec (4313 seconds)

Published: Tue Jan 12 2021