AVOID These Foods to Prevent Weight Gain & Diabetes from High Levels of Uric Acid | Dr. Perlmutter

you know one can only wonder why it was that the textbooks that we were given and the websites more recently of the major clinics have said no it's purines and alcohol and really kind of avoided what clearly is the biggest threat in terms of raising our uric acid levels and that is the sugar fructose sugar fructose is directly metabolized into uric acid and interestingly we've connected this dietary shift uh in human nutrition favoring much higher levels of fructose to the elevation of uric acid which puts this the body into survival mode and threatens our [Music]

health Dr promot we are back I am so excited to see you welcome back to a whole new level I'm I'm so excited I think we had such a great time last time we covered some really interesting information and you know it was several months back and there's been a lot of evolution in that science so I'm delighted to be with you I can't wait to talk about what's next uh for you what you're thinking about uh in health and our last episode together on uric acid we Dove deep into your groundbreaking book drop acid

that video has over three million views people were fascinated by that so I think just to kick off let's recap a little bit about uric acid people had a lot of questions more they wanted to learn let's just start with the basics why is uric acid so important and what levels should people be shooting for both men and women for optimal uric acid levels well you know an overview would be that U we always thought uric acid was something you needed to check in terms of gout you know if your uric acid level is elevated

then those crystals of this uric acid can um precipitate and out in your joints Etc and you get gout and it hurts and that's why you need to know your uric acid level that's what you learned and that's what I learned in medical school and uh it's true but what we were myopic about is the notion that uric acid is playing a far more important role than just giving us pain in the toes from time to time uric acid is a central regulator of metabolism and what I mean by that is that uric acid is

a way that the body is instructed in terms of so many different Pathways that are involved in the process of using energy uh using energy sources to create energy and so that our cells can can be vile and that's really very very important uh because of its Central role in metabolism it therefore regulates things like inflammation it even regulates things like uh the complexion of the gut bacteria who knew so uh this uric acid is a huge player in terms of our physiology and in terms of our pathopysiology across a wide spectrum of chronic degenerative

conditions well beyond gout including uh cognitive decline cardiovascular disease diabetes disregulation of insulin and elevation of blood glucose inflammation as I mentioned and even more interesting from my perspective based upon where my work is going these days that elevation of uric acid is damaging to the function of our cells energy providers called the mitochondria meaning that when uric acid level is elevated it's messing up the way our cells use fuel for energy and that is a bad thing uh I think that's probably what you and I are going to focus on for the next who

knows how long uh but the point is that um we need to know our uric acid levels just as as we need to know our blood sugar levels our average blood sugar levels our blood pressures our body weight Etc it's one of those fundamental parameters I have to say when um when drop acid came out and we presented 400 references about why this is reality uh I think it caught a lot of mainstream medicine offg guard um not recognizing that hey this is a new player that we didn't really understand in medical school uh but

now I think it's it's been really substantiated which is always good when you write a book that the stuff that follows supports your original hypothesis and contention so now people are getting their uric acid levels checked quite regularly more than just their annual blood tests we like to see levels in men and women and children at 5.5 or below now typically if you get a uric acid level from the lab the normal range is going to say anything below seven and that really relates to gout uh as it relates to cardiovascular risk and other things

that I had just mentioned those risks begin at a lot lower level at 5.5 and so we want to do everything we can to keep uric acid under control and you know to summarize brief which is I think what you're wanting to know what the what are the biggest inroads that these days are causing elevation of uric acid and you and I learned well it's these purines that are the breakdown products of animal products and and certain vegetables as well that contribute to make uric acid well we were steered uh off the scent off the

track uh for reasons that I we could speculate on because the reality is it's fructose it's a type of sugar that is ubiquitous now in the uh Western diet really the global diet now to sweeten up our foods and you know one can only wonder why it was that the textbooks that we were given and the websites more recently of the major clinics have said no it's purines and alcohol and really kind of avoided what clearly is the biggest threat in terms of raising our uric acid levels and that is the sugar fructose sugar fructose

is directly metabolized into uric acid and interestingly this is a survival mechanism for us that um in our ancient times when we would have fructose fruit fructose meaning fruit sugar it meant that because fructose comes from ripened fruit in the late summer early fall it meant that winter was coming a time of food scarcity and and having said that this is a way that our environment would cue us in to make some physiological changes so that we could survive when there was less food available so we eat the ripened berries that we might find as

we are hunting and Gathering and suddenly in our diets there's fructose and it triggers uric acid level to get higher and that higher level of uric acid does some important things in human physiology that allowed us to survive it allows our body to make and store fat which you know nowadays is not really deal but when you're facing uh starvation that's really very important uh it raises the blood sugar from in from turning on a process called glucon neo genesis glucose sugar Neo new genesis creation uh in the liver to give us more blood sugar

to power our brains so that we can avoid predation meaning we're not going to be a meal for somebody and starvation for obvious reasons and third mentioned it before is this elevation of uric acid threatens the function of mitochondria reduces our energy utilization which when we're trying to conserve calories is a good thing but nowadays we are triggering this survival pathway 365 days a year because of our constant exposure to fructose fructose is by far in a way the most widely used sweetener because it's really really sweet you don't have to use a lot of

it and it's really really cheap and our government tends to support uh the growth of corn uh which is from where you know we get a lot of fructose through the creation of something called high fructose corn syrup so you know I think back uh at a time in February 21st 2021 you when you and I wrote an oped in um was it Med page today I think right really just calling out the notion that you know we're supporting uh the provision of this D dangerous sugar to the American population and uh saying that it's

okay for 10% of calories to come from added sugar yikes that that was you know certainly good for the uh industry that's for sure but in terms of our health that is what sets the stage for our most pervasive chronic degenerative conditions that according to the World Health Organization are the number one cause of death on planet Earth so you know via this question we've connected this dietary shift uh in human nutrition favoring much higher levels of fructose to the elevation of uric acid which puts this the body into survival mode and threatens our health

so um you know it's where information becomes extremely empowering to to recognize that this is happening to read the labels to understand that there's 36 gram of sugar in a 12 ounce glass of orange juice from Florida with great vitamin C and fiber well let's let's be clear you know these are powerful onslaughts of uh and assault on our physiology with this incredible signaling molecule of fructose that becomes the uric acid which is where you and I started today if you've heard me talk on other podcasts before you know that I believe that tracking your

glucose and optimizing your metabolic health is really the ultimate life hack we know that cravings and mood instability and energy levels and weight are all tied to our blood sugar levels and of course all the downstream chronic diseases that are related to blood sugar are things that we can really greatly improve our chances of avoiding if we keep our blood sugar in a healthy and stable level throughout our lifetime so I've been using CGM now on and off for for the past four years since we started levels and I have learned so much about my

diet and my health I've learned the simple swaps that keep my blood sugar stable like flax crackers instead of wheat based crackers I've learned which fruits work best for my blood sugar like I do really well with pears and apples and oranges and berries but grapes seem to spike my blood sugar off the chart I'm also a notorious night owl and I've really learned with using levels how if I get to bed at a reasonable hour and get good quality sleep my blood sugar levels are so much better and that has been so motivating for

me on my health Journey it's also been helpful for me um in terms of keeping my weight at a stable level uh much more effortlessly than it has been in the past so you can sign up for levels at levels. link Health get access to a continuous glucose monitor and the level software that helps you really uh dial into a lot of these strategies for your life and your body you know a lot of people are out there right now confused about why do we have an obesity epidemic why are 50% of adults and upwards

of 30% of teens obese you know we're literally eating ourselves to death and a lot of the mainstream media would make us think like this is so confusing we don't really know why and I love that you really cut the noise here it's like hydris Corin syrup was invented in the 1970s it's now in most of the products in the grocery store it's creating uric acid damaging our mitochondria causing us to not use energy properly we 3D print fat and it's a weaponization of a non-natural form of this molecule that is damaging the fundamental way

that we power our bodies and therefore shunting us towards fat storage which like you said in the past that would have been useful for an animal preparing for winter and needing to hibernate and build fat but right now it's playing out every day at every Breakfast Table in America and you are sounding the alarm on what's Happening and how simple this is to actually get on top of uh with food so I'd love to talk a little bit more in detail about diet because we got a lot of question after our first episode about what

do people really need to be eating what I'm hearing here is we need to cut the liquid fructose uh obviously but what about the fructose and fruit this was a big question we got does the natural fiber and fruit you know mitigate this that we're this this issue we're dealing with with fructose is it really the high fructose corn syrup we need to worry about how should people think about fruit when it comes to to uric acid it's a great question let me first say we've got to stop drinking fruit juice can you imagine a

doctor saying that yes we've got to stop drinking fruit juice and we've got to stop giving it to infants in their bottles I mean that is absurd is fruit something we should consume I think yes you know I think an apple a day is a good idea we've known known that aphorism for a long time uh because there really isn't a huge amount of fructose in an apple depending of course on the size and the and the type of apple but it's about five grams and as you mentioned it is delivered in a way that

it does uh slow its availability because of the fiber and because vitamin C that apples contain also helps us excrete uric acid so have an apple or two a day it will keep the doctor away uh and and you know it's not an onslaught our small intestine can handle about five grams of fructose at any given moment but you know when you suck down a Big Gulp or you know whatever is you you know a soda that you uh that is your favorite some of them have incredible amounts of sugar I mean it's mindboggling and

energy drinks sports drinks you think well I'm going to the gym and having a sports drink I I watch that happen at at my gym because there's a vending machine and you know you talk about offsetting the the value of your workout that's a really good way of doing that uh it's it's a huge uh override in terms of what the small intestine is able to deal with so that fructose is absorbed and then is directly shunted to the liver where the processes that I just overviewed are activated and um it's you know it's very

very worrisome I think uh I I really want to call out good energy because you did such an excellent job in that book you and your brother of really just making it very clear what an assault this has become on our health and importantly our children's health I mean we are just you know setting children up for all all the damaging metabolic issues that are so pervasive in adults and you know I have to say people say to me when should people start the Alzheimer's prevention diet because we know that and I'm being a bit

tangential here I understand we know that the metabolic changes in the brain take place 20 to 30 years prior uh to the beginnings of cognitive decline and again let me let me reiterate that that what's going on in the Alzheimer's brain begins two to three decades prior to forgetting the Wi-Fi code and your grandchildren's names that's when people seek assistance from a doctor for a medication which does not exist so these issues take place two to three decades ahead of time so I think the answer you would expect from me is when uh to respond

to when should we begin the Alzheimer's prevention diet well maybe it's two to three decades prior to when Alzheimer's typically present so maybe we should start paying attention in our 30s and 40s and I won't respond with that answer any longer uh for reasons that you and your brother called out in good energy and that is because of what's going on with children that we are setting the stage for metabolic dysfunction in adolescence uh in children and uh even in infants uh and you know the reality is that there are things going on in utero

that play a role uh in an individual's lifelong metabolism that are important important and are modifiable and even method of birth is important as it relates to inflammation in the body and Metabolism vaginal birth versus cerian section we live in a country where about a third of births are csection uh and it's clearly hard to imagine that there that a third of pregnancies are that complicated that a C-section is required I think that there are other reasons that C-sections are so prevalent here in America America but understand that the mode of delivery is really fundamental

as it relates to the influential microbiome I.E the bacteria living within the gut and upon the surface of the body and in the mouth as well these are all highly influenced by the method of birth when a child is born vaginally that child is Anointed with a specific set and array A diversity a functionality a family of organisms that sets the Ste seeds in place to grow that microbiome when a child is born by C-section then he or she gets bacteria from whatever is floating around the operating room or on the surgeon's gloves or gown

and those are not necessarily one would expect the the best for the developing microbiome of that newborn it's the reason we see the correlations of cerian section with significantly higher risk for things like autoimmune conditions uh including uh type 1 diabetes so getting right back to metabolism so you know when do we begin the inflammation Alzheimer's metabolism diet and I think uh very very early and again I want to thank you for calling that out uh in good energy yes in utero I mean I love that and it's just so important um yeah and it's

such an opening thing you know I'm I'm in the year two before you know hopefully having children and I'm just so much of what I think about now which I was not thinking about 10 years ago when I was in the conventional Health Care system is how is my diet and lifestyle actually setting me up to be able to have ideally the most natural birth possible because of what we're learning about you know modifiable factors in mothers and in pregnancy method of delivery and then lifelong metabolic uh trajectory for kids and so I just I

love that you talk about that and and find a way to weave all of this together in such a beautiful way I I would say that uh this method of delivery discussion is profoundly important and you know the issue is that um how a woman chooses in terms of uh lifestyle uh issues prior to delivery really sets the stage for complications or not you know depending on is she exercising is she sleeping enough what's her alcohol intake what are her her medication's looking like what her Recreation drugs are looking like uh so many factors I

mean uh you know go into whether or not that's going to be a a healthy pregnancy and therefore more likely to end up as a vaginal delivery so these are you know it's not well you need to take a multivit make sure you got a lot of folate in there and uh um and we've got to do better than that we've really got to emphasize to women that what's going on during that pregnancy and delivery are going to be fundamental as it relates to that in new child new human being's health for the rest of

her or his life and uh there's a lot to discuss there and you know I think that the notion of just capriciously recommending a C-section without the discussion of the long-term consequences you know saying well you know you'll have a scar and then the next child maybe that has to be C-section because you did one we got to do better than that I believe beautiful so a couple other questions that got about diet and uric acid there's definitely a trend towards people being very passionate about regenerative meat and keto and carnivore and just eliminating the

sugar Al together but as you said you know purines and these foods that you know uh animal-based products can also cause the production of uric acid but you alluded to that really not actually being the core of the problem it's the fructose so what would you say about different diets like keto and carnivore and how they impact uric acid levels and how can someone on these diets think about their uric acid levels and how to manage them effectively I I think that as it would be with uh measuring blood sugar I think it really depends

on how any particular diet is affecting that individual I.E they should be checking their uric acid levels and see we do know that an aggressive ketogenic diet can in fact raise uric acid transiently uh that that seems to subside and actually then improve based in comparison to Baseline once that hardore or ketogenic diet uh is is Left Behind uh certainly fasting because of the fact that tissues are being broken down will liberate purines from the cells of the of of your body as those tissues muscle in particular are being broken down and will raise uric

acid but fasting ultimately seems to improve uric acid in comparison to Baseline as well but again as it relates to what would be the best recommendation I think this is where personalized medicine comes into play knowing that we can check our uric acid levels at home with a simple finger stick and if we decide we're going to make a significant dietary change that would be something along with looking at your blood glucose that you'd want to know how is this new regimen affecting my blood sugar and how is it affecting my uric acid level and

some people will actually say that on a ketogenic diet they actually will tolerate a slightly higher fasting glucose level so like upper 90s maybe even low hundreds because insulin is so low and it may be having an impact on glucano Genesis but not in a pathologic way do you find that there's anything with like that having a slightly higher uric acid level on a particular diet if it's an otherwise very metabolically healthy diet very low insulin levels you know that that there's some leeway there or do you really want to see people pretty firmly in

that tighter range below 5.5 most of the time I I think that 5.5 is not respectfully is not really tighter range I I think that when we look at what happened as average uric acid levels have climbed dramatically since the 1920s uh in lock step with fructose consumption I might add or sugar consumption prior to um hus corn CH becoming so ubiquitous so I think that we're that at 5.5 is not really aggressive it was a level uh that you know I and Dr Richard Johnson settled on based upon uh review of literature and also

what is easily pretty easily achievable by by most people having said that there are some uh interventions that people can engage uh that if there is a bit of a recalcitrance of that uric acid to come down based upon the current diet uh can be leveraged in hopes of bringing that uric acid level down a little bit further they include the addition of things like quatin quatin 500 milligrams per day along with lud diolan 100 milligrams per day perhaps uh some vitamin C 500 milligrams per day these are really very helpful in you know in

finalizing you know getting that last little push to get that uric acid level down so you know you can expect maybe half a point or I've seen some people as much as a full point drop just by starting those nutritional supplements so but I think 5.5 is typical I mean there are some people who have uh polymorphisms of Eur at one uh Gene and and as such are going to have by virtue of their genetics going to have higher uric acid levels and these are the people who despite the supplements and the dietary changes still

have significantly elevated uric acid and they may need medication you know they may need something called alopurinol and I I'm in favor of that even if they haven't had a gout flare up I think you know when you see a patient with a buric acid level of seven or eight who's on a low fructose diet maybe taking some course Etc I think it needs to be treated because you there are a lot of Downstream consequences even high blood pressure related to having elevated uric acid so uh you know uric acid by virtue of the fact

that it stimulates lipogenesis the formation of body fat ultimately will lead to increased production of metabolic water and actually through that mechanism and through a mechanism involving something called baso pressent actually increase blood pressure so um I I can think of several individuals who just by lowering their uric acid had improvements of uh their blood pressure very interesting great to hear those actable suggestions too with supplements if people have some some MC acid that's having trouble getting you know into the levels they want um I'm curious being a neurologist a metabolic health expert a uric

acid expert amongst many other things your thoughts on alcohol because I know that beer in particular can have an impact on uric acid but as you triangulate all these different fields that you think about so deeply where have you landed on alcohol as it pertains to both uric acid metabolic health and risk for dementia haven't landed on alcohol maybe later today I don't know you know my position has changed a bit over the years and that's a good thing uh that we change our our messaging based upon research uh uric acid is made from alcohol

but I think it's um it's like fat uh when we talk about well you should eat fat you shouldn't eat fat well no we need to talk about what kind of fat and this the same kind of um Paradigm exists as it relates to alcohol that uh in women more than men there's actually a benefit of drinking wine in terms of lowering uric acid within reason two drinks are two glasses of wine men don't really get that benefit hard alcohol tends to raise uric acid pretty significantly in both men and women and beer being uh

the worst beer is the most offensive raising uric acid quite substantially the thought being that yes beer is an alcoholic beverage but beer contains a lot of those purines the breakdown products of cells because it's uh made with brewers yeast and yeast is a very hyper cellular kind of thing so you're getting both purines and alcohol in beer uh and interestingly in Japan they've known about this for quite some time that it raises uric acid and have now created purine free beer so you know beer has significantly less alcohol then heart spirits and and uh

wine pretty much so you know there may be a way having said that I think there's no alcohol that is safe during pregnancy uh and uh you know it used to be well you might have a glass of wine or to the benefits of the relaxation Etc are good uh my vote is that women do not consume alcohol during pregnancy and uh I think that adults uh should be reducing if not eliminating their alcohol consumption there is an upside of the socialization and perhaps some of the polyphenols in red wine I get that but I

think the um the neurotoxic effects of alcohol are very real and we can no longer ignore that so my vote is that uh that we should really minimize our alcohol consumption okay that's right feel like I'm landing more and more as well just just you know I feel like sometimes there's this confusion around or not confusion it's just it gets complex with like okay some wine may help with metabolic Health but you know how is that data done and then the neurotoxic effects for dementia and I mean overall it feels like the the train is

moving towards we're drinking too much as Americans we're just drinking far too much and we need to be reducing or getting closer to eliminating um and uh so it's really helpful to hear your perspective on that yeah if you drink two glasses of wine a day it doesn't seem like a lot you know fill it up once and then one more time you are considered a moderate alcohol consumer that's moderate alcohol consumption and you know when when you read the literature what is moderate alcohol consumption associated with so again so I think that your positioning

or change in positioning is is reasonable yeah um so I'm curious sort of closing out the conversation on York Gast and moving some other topics around gut health just just curious you know the other aside from hutus corn syrup that has been skyrocketing and sugar intake uh you know of this liquid form we've also been eating so many refined grains in our country do refined Ultra processed grains like white flour that's in so much of the processed food does that have any impact on uric acid or because it's not actually fructose that it's converting to

in the bloodstream it's less of a impactor on on this one like gluten refined grains uh uh here's the answer to that anything that raises blood sugar will ultimately increase fructose and raise uric acid why so because we have a survival pathway in the body called the polyol pathway and through the action of a an enzyme Aldos reductase if anybody wants to put that on the quiz uh we are actually able when blood sugar is elevated to shunt some of that blood sugar glucose uh to actually form fructose and that fructose then as mentioned metabolized

in uric acid so you know these are the things all of the things that you've been talking about for the past several years that will raise blood sugar including these Ultra processed foods will actually raise uric acid as well through this and and other Pathways um and you know it for me it it really closes the loop to then understand the relationship between these ultr processed foods now making up about 58% of calories consumed by the average American adult on a daily basis 58% coming from these highly ultra-processed Foods it really helps us close the

loop and understanding the relationship of the consumption of these foods to the metabolic issues like uh brain changes and cardiovascular disease and certainly type two diabetes and weight gain that we see uh we know there's a relationship between cons higher consumption of these Ultra processed foods uh and even risk for certain forms of cancer and the cognitive issues and threats to the brain begin at a much lower level uh it probably all all of the other issues do as well but but I'm referring to a recent article that looked at even 28% of calories coming

from multra processed foods poses a significant threat why so for the reasons that I mentioned but also because of what elevated blood glucose is going to do and I think um you know and I knew we were going to get together today I think it's really kind of valuable to ask ourselves well then what is the mechanism here we we say that having an elevated blood sugar is a bad thing for the brain that's what we'll talk about but why I mean what in the heck is going on uh in the brain maybe we could

go there or but but maybe you have a different agenda so I don't I don't mean to steer the conversation oh no I love that I think that I would love to talk about that because I think that's going to really lead into talking about the brain's immune system inflammatory triggers metabolic Health which I know you're thinking about so I will I I will Circle back to that for sure at the end of this conversation I just I know people are going to want to know this question how often should I check my uric acid

and how can I check it what's the sort of quick high level on on how people should be thinking about testing well you could buy one of these things this is a uric acid Monitor and there I don't know if that's backwards or forwards that's my last level I don't know if you 4.7 yeah and so this is you know you put uh you put a drop of blood on a strip it's in the machine and you get a reading right and uh so it's really quite simple and I think every six weeks weeks every

eight weeks is reasonable unless you engage in some kind of you know significant dietary change and you're curious I think that's perfectly reasonable uh I would recommend that when you do check your uric acid levels at home a couple of things first good to have a a lab value at a regular Lab at the same time so do it when you're getting your blood drawn once at least making sure that we're reading apples and apples the other thing I would say is that night before don't have alcohol and that day before don't really push the

workout especially uh anything you know in extreme that might break down muscle tissue like weights or you know maybe running a little further than you normally do because that will liberate per and you increase of uric acid so um you know that's how often you can do it and get a sense as to what direction you're going if it's elevated you know you want to check it more frequently make sure you're going in the right direction perfect and I think that monitor that you just showed people can get on Amazon it's pretty easy to get

very inexpensive yeah this one's called U usure and uas there are several on the market nothing could be well I guess something could be easier but you know for those of us who used to check our blood glucose levels with a finger stick it's uh you know it's second uh it's second nature that's great that's perfect and then levels Labs because of your advising has added uric acid to our panel so that's something that people can also get through the levels panel as well or asking your doctor for it at a physical so that's amazing

thank you for answering those questions about uric acid I'd like to shift gears to one of the many things you have so much expertise in which is gut health um because I think there's still there's still confusion about the relationship between gut health and metabolic health and you've written the books on gut health and how it relates to metabolic health and brain health um I will say that I have had several conversations the past year with academic Physicians who believe that the concept of leaky gut is pseudo science when I use the phrase intestinal permeability

it gets a little more traction which is basically the same thing but can you give us the overview of what is leaky gut how do you address the skepticism from some people regarding this idea of leaky gut and why does it matter for people listening well first I would say to you Casey that people are down on what they're not up on uh and that that rings in my mind when I hear such skeptic ISM and you know the reality is we've been talking about the term leaky gut actually for about a quarter Century now

with people who you know I mean Dr Bland uh at ifm um you know this was we've been talking about this for decades and uh because it seemed very clear that anything that assaulted the Integrity of the gut lining seemed to be at least in those days associated with other non-gut related pathologies or pathological conditions uh but I think in the past 10 years or so we've really begun to connect the dots and get a really good understanding uh through some really wonderful researchers like Dr alesio Fano for example at Harvard that permeability of the

gut is really Central to so many of The Chronic inflammatory conditions well let me be clear first what is a chronic inflammatory condition is that some kind of you know rare uh exotic disease no chronic inflammatory condition means we're defining a mechanism that underlies Alzheimer's Parkinson's uh certainly a type 2 diabetes um various forms of cancer various forms of uh inflammation in the body like arthritides or type many types of arthritis for example autoimmune conditions as well uh so we are understanding that the set point of inflammation how high it is at its base is

very much regul ated by uh what is called the gut Associated lymphoid tissue or gt meaning that clustered around the intestine are many cells of the immune system most of the important cells of of our immune system most of them live in Ju toos to the gut why would they be there they are there because that's where they get information about the environment that molecules come through the intestinal lining and tell the uh uh immune system what in the heck's going on in the environment so that we can adapt we can increase the production of

inflammatory chemicals at times that's a good thing to Keep Us Alive uh we can regulate our immune system so that it's not overactive and we don't develop an autoimmune condition in a situation where our immune systems are reacting against our own tissues like type 1 diabetes celiac disease lupus rheumatoid arthritis ankle losing spondilitis the list goes on so the immune system is very much in touch with the gut to receive signaling from the external environment far more so than is associated with respect to the air that we breathe though a very similar mechanism is happening

in the lungs but by far in a way the largest representation is this relationship between our immune systems and what is going on within the intestine now the intestine is very selective in terms of what it delivers to the immune system such that the immune system can then do what it needs to do to Keep Us Alive but that selectivity of in terms of what is presented to our immune cells uh is controlled by what comes across the gut lining normally that is very very tightly regulated there are guards at the gate to keep Invaders

out such that we don't challenge the immune system there's 's a very tight network of connections cellto cell that are very selective in terms of who gets in and who doesn't now we can threaten those connections we can increase the ability of things to get in and then challenge the immune system when we damage the gut lining first we can directly damage it with the ingestion of various chemicals primarily the types of drugs that we might be consuming and to a a second uh dairy uh degree uh in many people the types of foods that

they are consuming but keep in mind that the master Regulators of the gut permeability are the bacteria living within the gut this is one of their most important functions and that is maintaining gut wall integrity and there are various species that are directly involved with that like lactobacilus plantarum for example and the new kit on the Block and acromium eosinophilia these are bacterial species that are involved in the maintenance to keeping those walls up to keep the Invaders out when I say Invaders I mean all kinds of things yes pathological organisms that for sure but

even the breakdown products of some of the normal bacteria that live within the gut that normally stays in the gut but when the gut is permeable those products of bacterial breakdown can make their way in uh through the wall challenge the immune system and set us up for big issues so it's sad on the one hand that um mainstream to some degree has not fully embraced this I mean you know there are drugs available to treat your autoimmune disease that will suppress your immune system uh you know there are these monoclonal antibodies that we see

advertised each and every night on television to treat your psoriatic arthritis or Crohn's disease or whatever it may be but we have to ask the question why is the immune system overactive in the first place and the literature that connects those issues and virtually every other autoimmune condition with permeability of the of the gut goes back an awful long time that's Upstream of the activation of the immune system that's where we should be focusing our efforts so that people don't have to take these monoclonal antibodies and experience the risks that are that are described in

the 60-2 commercial when they change the visuals to something really cool and you're looking at people doing great stuff when they're reading off the list of all the things that can happen when you start using these drugs so you know I think I'm reading from the good energy Playbook here but uh but that said that's why maintaining a healthy gut and as such a healthy gut wall Integrity is really so fundamentally important across the entire spectrum of these types of health issues just out of curiosity do you do is there an estimate that we have

a sense of I know it's hard to do this like to understand how many people might be dealing or sort of really on the spectrum of leaky gut in our country or more broadly like what percentage of Americans based on lab data do we know have sort of more inflammation going on in the body than they should well I think you know the answer to the question because I think you're very familiar with the number of people uh in America who are metabolically intact and that number is very small probably what 5% of adults so

I would say that probably 95% have a situ are involved a situation where gut permeability is not ideal uh it's not as if we have a direct uh metric for gut permeability that we can get in the blood and it's part of a panel uh but we can infer permeability of of the gut by looking at surrogates like blood sugar like body weight like inflammatory markers catic protein sedimentation rate these are all indicators of either directly of INF infation or as it relates to blood sugar and hemoglobin A1c the likelihood of inflammation so I I

would say anyone with who's metabolically compromised I.E almost everyone uh likely has some degree of of hyperpermeability it's astounding and I think you know I I think about children and how so much of the culture that's normal for our children today really sets them up for gut dysfunction and what I'm hearing from you is that it's not just direct assault to the tissue to the colon and the small intestine tissue it's also anything that's hurting the microbiome so both damage to the tissue or lack of resourcing to the tissue and also anything that hurts or

resources the microbiome can have an influence what would you say are the top few things like if we're talking to an adult or a parent of a child um the top set of things we can do to support really high quality gut lining and avoidance of leaky guide or healing of heat leaky guut well the first three would be uh dietary fiber dietary fiber and dietary fiber uh there are a few more that follow after that but you know that is the component of uh in the global diet now that is suffering and we we

spoke earlier about these Ultra processed foods yeah they're Ultra processed because we're processing out the dietary fiber you know I I've heard comments recently as in last uh yesterday afternoon that in know average uh American is consuming maybe two or three grams of fiber a day which is uh the reason it's important is because that's what nurtures the gut bacteria who are then going to shore up the gut lining but you know the fact that we're not consuming dietary fiber is a major major threat and that's again from the uh this pervasive consumption of ultr

processed foods that's the biggest issue I mean we know that various medications that are taken so liberally like non-steroidal anti-inflammatory drugs and acid block blocking drugs and artificial sweeteners as well not a drug but things like aspartame are clear and present dangersous as it relates to the health functionality and diversity of of the gut organisms there are a lot of things that um are not necessarily diet related we know that there's a significant change for the worse uh in the array and functionality of got bacteria if we don't sleep well uh we know that stress

increases cortisol and cortisol changes quite dramatically the milu within the gut there a lot of factors that people maybe don't come to uh bring to mind right away that are involved in changing the gut bacteria as well U certainly uh a big issue especially as it relates to children but adults as well in America is the incredible overuse of antibiotics me antibiotics are weapons of mass microbial destruction and we have the tech technology today to absolutely specifically determine what is the organism that unique organism that's causing a particular infection at in some point of the

body some part of the body we have that technology it's not widely used we can sequence and determine what is that organism and uniquely Target with a very narrow spectrum antibiotic what it will take uh to uh eradicate that organism if it's a pathological issue in fact I reviewed a study that came out this morning talking about the use uh the uh the development of a uh an antibiotic uh for gram negative infection that apparently had no effect on the microbiome um that's going to be a little bit challenging for me to appreciate since most

of the organisms in the gut are gram negative at least bacteria but beyond that um at least people are thinking about it that giving anti antibiotics that are broadspectrum are you know as I mentioned Weapons of Mass microbial destruction we need incredibly focused narrow Spectrum antibiotics for a number of reasons uh first because of the effects on the gut that we talked about with a a wide spectrum antibiotic and second because it would dramatically reduce the notion of antibiotic resistance which uh is becoming you know ever uh more of an issue for us to to

be aware of and and yes fear that we may ultimately be in a situation where infections develop with organisms that are widely resistent to the armamentarium of antibiotics that we have so the technology is there I mean and in fact uh you know there is very old technology that needs to be revised and it's called Fage technology we know that these viral particles called fages uh can be manipulated and created in such a way that they can be uniquely targeted against uh specific bacterial strains that may be a pathological and really you know uh as

has been demonstrated since the 1920s are associated with only minimal side effects if any incredible um that's so so practical and helpful fiber fiber fiber so I carry a bag of flax crackers with me everywhere I go uh but you know it's also astounding with the antibiotic conversation I when I was in residency and my lifestyle was a mess and I was getting sick I had sty in my eye and I had acne come back you know was went away after teenage years and then came back when I became metabolically dysfunctional and residency both conditions

the doctor the opthalmologist and dermatologist recommended three months of doxy cycline which is an antibiotic you know as you know and I said no to both knowing even at that time what I knew about the overuse of antibiotics and obvious you know both both went away and I just can't I my my life could actually look somewhat different I don't want to be Sensational asra alarmist but you know six cumulative months of antibiotics has a does a number on your gut for probably years and so it's just you know there's there's often other Solutions um

and of course we should save the antibiotics for situations where it could potentially be serious and life-threatening I am all in you know and uh getting back to a topic we had uh we discussed earlier that is C-sections require not that they require but as standard part of a cerian section is giving a blast of intravenous antibiotics we need a paradigm shift so in our last 10 minutes or so here I would love to shift gears to talk about what I know is something that uh a new area of interest for you that you're really

diving into and your mind is so beautiful and you're always on the Leading Edge of of what's important I think for health and so I'd love to hear a little bit about what you've been thinking about regarding this Nexus between the immune system between metabolic health and between specific cells in the brain that seem to be mediators of both inflammation and and metabolic health and what what we can kind of learn about metabolism through this study of microa and I just would love to hear your perspective on how this has unfolded for you as a

area of I shouldn't say new area of interest but so there's a term called imuno metabolism that I I I just think is a beautiful term because it relates the function of our immune systems to our metabolism but also lets us begin to understand that how our immune cells metabolize in other words how they make energy uh regulates how they function that's maybe people don't get it yet but let me walk through it because it's it's huge in terms of what you and I are going to talk about a year from now uh and five

years from now it's really very very important because it turns out that the metabolism of various immune cells regulates whether they're going to be helpful or hurtful whether they will be the angel or the Assassin uh in the peripheral uh part of our body we call them the macres and they exist in multiple forms but for uh ease of conversation we'll say uh M1 form and M2 form M1 is the evil twin M2 is the good twin we want to keep our immune cells uh in the M2 configuration uh such that they do good things

for us the M1 form does not such good things for us now the an analogous cells in the brain to the macres are called micro gal cells and you know when I grew up those were considered supportive cells in the brain that kind of were a bit of a scaffolding of the brain we didn't really understand that they were the brain's immune cells and more recently that they can change between M2 and M1 as well they can go between being very supportive nurturing the neuron gobbling up bad proteins like beta amalo being supportive of the

synapses where one brain cell connects to the other or they can shift when their metabolism has shifted their mitochondria have become less functional to the the evil twin the M1 form in which case they're not supportive of neurons they're in fact damaging to the neurons they destroy our synapses they destroy the connectivity of one brain cell to the other they actually enhance the formation of damaging proteins like beta ameloid all as a consequence of the shift from being helpful to hurt hurtful and this shift again is triggered by a change in their metabolism so what

we're exploring now is what is it first that's changing the metabolism of these immune cells in the brain and in the periphery as well and uh many of the things that people are well aware of higher levels of blood sugar for example infections can do it uh inflammatory chemicals in the body I.E inflammation from anywhere in the body I.E leaky gut can relate back to the brain and change these important cells that make up about 10 to 15% of the brain cells that are involved in maintenance that can change these cells from being friend to

foe think about that that's the relationship then between for example a higher consumption of non-steroidal anti-inflammatory drugs uh and leaky gut and problems in the brain it's a relationship between taking acid blocking drugs and increasing your risk for Alzheimer's disease significantly when you are using these drugs you're increasing gut permeability increasing the production in the body of these inflammatory chemicals that changes in the brain how these cells go from being good to bad now we're accumulating beta ameloid we're damaging the synapses we're not nurturing uh the neurons any longer because these cells have been changed

in what we call their phenotype and in terms of their metabolism so what you want to do is ask then if that's going on well is it reversible and it is reversible it's challenging but it is reversible and there are various things that can be brought to bear that can reestablish these cells and bring them back to being helpful not hurtful and basically it involves targeting their metabolism importantly targeting how they are able to use energy how their mitochondria work and we get to a situation of trying to understand what are all the cool things

that we can do to enhance mitochondrial function we all remember from high school energy that these mitochondria are the energy producers in the cell they're the they're the what is involved in metabolism they're taking in glucose and they're making energy in the form of ATP how can we enhance their ability to do that well fasting ketogenic diet we know that acromania musop is a a probiotic that may actually Target that uh so there are a lot of things that we can be looking at uh quatin uh various exercise for example there are a lot of

things out there that look like they work and may have um May ultimately have Traction in terms of what they're able to do to turn on metabolism now when you ask anyone these days what's hot in metabolism what are people going to tell you gp1 Agonist yeah OIC like drugs it turns out that these drugs that stimulate gp1 uh that there are glp1 receptors on the M on the microa and when you stimulate those glp1 receptors on the microa you improve their metabolism so where are we going with this well we're going to a place

of the idea that increasing glp1 might well be something really really good for the brain we saw I guess two months ago published in New England Journal of Medicine an Interventional trial over three years where a glp1 drug and o zic like drug was used in Parkinson's disease patients and virtually arrested the Parkinson's a generally considered chronic progressive means it worsens with time disease as any Parkinson's patient will tell you we have no drugs to treat Parkinson's zero we have drugs that we've used for decades to treat the symptoms of Parkinson's we treat the smoke

we treat the Tremor we treat the rigidity but the underlying fire has never been approached until now these studies demonstrate that Parkinson's not only can be arrested but in the study published in New England Journal of Medicine these people taking this drug actually showed some slight Improvement uh in their Parkinson symptoms as was revealed on the unified Parkinson's disease rating scale in other words there's a scale by which researchers around the world are able to to metrize the symptoms of Parkinson so how the drug works is by targeting metabolism of these microgo cells and interestingly

some of the worst things we can do for our microa are allowing our blood sugar to elevate and allowing us to become insulin resistant that immediately tends to shift those micral cells from being friend to fo so for all of those who are interested in looking at their blood sugars and doing the best they can to keep their blood sugars under control that are wearing continuous glucose monitors and having their a1c's checked frequently this becomes uh really important through the notion of understanding what you are doing to change either for the good or for the

bad the function of these brains immune cells micral activation in other words the shift from good to bad is Central to chronic neurodegenerative conditions like Alzheimer's like Parkinson's like multiple sclerosis we see it in autism as well we can even image these cells in Vivo in living people these cells can now be imaged when they transform from being helpful to hurtful imagine that in terms of a a diagnostic tool but in terms of a research tool to be able to see if your intervention like caloric restriction like exercise like using metformin or or using quatin

or Minocycline or whatever it may be to see if it's working in it see if it's helping people using an extract of licorice for example all of these things are being explored in terms of being able to revert those damaged I call them damaged or dysfunctional microgo cells back to being helpful uh back to being in a form that's going to be useful our research right now uh is looking at uh Hyperbaric oxygen you know when we talk about what do the mitochondria do when they're functioning fully uh in the helpful form they're using oxygen

to create energy interestingly when they become the evil twin the M1 phenotype they shift away from using oxygen to process uh glucose to using a different process in the cell called glycolysis which is not aerobic metabolism does not use oxygen but what we're seeing is people have improvements in in the function of their brains when they get hyperbaric oxygen treatment and I think what we're going to see in fact I'm meeting with a research team next week is that once we begin Imaging these individuals in terms of their microa we're going to see that they're

shifting back to being the M2 or helpful phenotype so I sure hope that was not too complicated let me see if I can summarize it real quick the brain's immune system is really important in terms of keeping the brain healthy normally it functions to keep the neurons happy the synapses established uh and clear away debris those cells can shift and do just the opposite threaten the health of neurons threaten and Gobble up synapses and uh actually lead to accumulation of bad misfolded proteins like beta ameloid we want to keep that shift from happening we do

so by maintaining our metabolic health and keeping the gut healthy but beyond that we are developing the tools now to shift them back from being foe to being friend incredible incredible I could I we could do an hour on that that was beautiful but I think you know something that I think was interesting during covid and and even in the aftermath you know where I think a lot of people are there was a couple months earlier this year where I feel like everyone was sick for like several weeks everyone's thinking about how do I support

my immune system and something that I just kind of want to yell from the RO Toops is that like every immune cell in your body also needs energy to to function properly so metabolism doesn't just affect your liver and your blood vessels it affects every cell and so well-powered immune cells are going to do better work and I think that's all over the body and and what you're talking about is also in the brain if we have insulin resistance in our bodies it's not in one place it's everywhere and kind of what I'm hearing you

say is that when we're insulin resistant it's affecting the brain these cells these microa are not getting the power they need they're underpowered they're mitochondrially dysfunctional they going to change their activity because they're on a totally different program and that shift in activity is going to lead to them not doing the helpful things that protect our brain it's you know cleaning up the BET ameloid and all that and so fundamentally to get ourselves out of that we have to figure out a way to have these cells you know make be mitochondrial functional make good energy

be insulin sensitive which means you know the holistic support of metabolic Health um and I I'd be curious maybe in our La last question here you mentioned exercise you mentioned reducing leaky gut there's dietary strategies to improve insulin resistance like for people well I guess one I I I'll try and keep it focused because I know we only have a couple minutes but what about sleep how does sleep impa your microa well there are a lot of mechanisms um we know that uh sleep is uh lack of restorative sleep not just adequate amount of sleep

but uh the amount of restorative we sleep we uh that we can get which we can measure using any one of a number of wearable devices but lack of restorative uh sleep directly increases inflammation in the human body number of mechanisms it also threatens the microbiome and that also increases the production of these inflammatory chemicals these inflammatory chemicals are uh observed by these micral cells and this is a powerful stimulus for them when they bind to the surface these micral cells it activ Ates um something called the uh nlrp3 inflammosome that'll be on the quiz

as well but it basically it activates a surface receptor on these microa that ultimately changes genetic expression of these microgo cells and ultimately threatens their mitochondrial function so this is the connection then between inflammation and changing uh microG glal functionality and in this case how sleep is involved with that sleep ALS also compromises the a lack of sleep rather the ability that we have to rid the brain of the accumulation of various types of debris including a damaged cellular debris and accumulated misfolded proteins Etc that happens during deep sleep when we activate something called um

you know very a pathway in the brain U that is involved it's called the glymphatic system that's involved in clearing the brain of these harmful chemicals when they accumulate within the brain they bind to receptors on the micral cells uh and these they're various receptors but uh there are things that bind to these receptors that are called damps damage Associated microbial patterns and pamps pathogen Associated microbial uh patterns binding to these receptors and and instituting these changes in the micral cell one other thing I'll mention because things really interesting what we're doing here you and

I we're tying up all of loose ends that all these hanging ad that we've had for all these years how in the heck does it work and here's another connection that I think you'll resonate with there's a very important receptor on the microa that when it is stimulated uh leads to these damaging changes and reverts them to their M1 bad phenotype and it is called The Rage receptor I love the name the rage so you bind that rage receptor uh with these various things that accumulate when we don't sleep well enough getting back to your

question you bind the rage receptor when you activate that rage receptor it is very threatening to the metabolism of the microa which we cannot afford now interestingly where did the rage receptor get its name the rage receptor got his name because it's the receptor for advanced glycosilated end products so I know you're getting ched right now because I am um these are the proteins that are modified by binding glucose when our blood sugar is elevated so now we've just connected some important dots some missing pieces of the puzzle another way that elevated blood sugar is

so damaging to the brain yeah when blood sugar is elevated we know that it increases inflammation and it also compromises insulin functionality we get that those are great mechanisms but the fact that we glycate our proteins like hemoglobin A1 see the fact that we glycate our proteins in the brain and that signals it's picked up by a receptor on these micral cells that makes them turn from being the good twin to the bad twin uh that is a powerful mechanism that argues so strongly for us to keep our blood sugars under control um and so

you know to me I I guess my excitement is obvious but gosh because you wonder about this stuff uh maybe not everybody wondered about this stuff to be fair but uh many of us do and uh but to have an answer to that question I think is is very exciting [Music]