Is Alzheimer’s Reversible? Getting to the Root Causes | Dr. Dale Bredesen

calling someone alzheimer's is like saying late stage cancer metastatic cancer because it's a very late stage of this process that's been going on typically for 20 years [Music] welcome to the doctor's pharmacy i'm dr mark hyman and that's pharmacy with an f-f-a-r-m-a-c-y a place for conversations that matter and if you have a brain you better listen to this podcast because it's going to matter to you because it's about how do we prevent and even reverse the worst condition that afflicts humanity which is alzheimer's and dementia and neurodegenerative disease in other words our brains are facing an onslaught of insults that are treatable that can literally reverse and even prevent diseases like alzheimer's and parkinson's which sounds kind of crazy because everything we've done hasn't worked and today our guest is an extraordinary doctor a friend of mine a pioneer in the field of neurodegeneration who's broken ground that few have treaded on and it's none other than dr dale bredesen who you may remember from our previous podcast where we discussed his book the end of alzheimer's his latest book is called the end of alzheimer's program which is a much more robust programmatic insight into how to actually use the protocol that he uses with his patients that i use and how we can tailor it to anybody at any age in any part of the journey along protecting your brain or fixing your brain he's uh been on the faculty of ucsf ucla university of california san diego he's directed the program on aging at the burnham institute before becoming to the buck institute in 1998 as his founding president and ceo and he's currently a professor at ucla and the chief science officer at apollo health which is a great online platform for addressing neurodegenerative disease so welcome dale thanks so much for having me on mark i really appreciate it okay so so let let's get into this because you know most people um worry about heart disease or obesity or diabetes uh but it doesn't take away who you are alzheimer's takes away who you are neurodegenerative disease takes away your soul in a sense uh your memory which is really what we're made of is memories and and i think that it's a terrifying disease for so many it's it's growing in scope it's affecting millions and millions of americans i think about 5 million now projected to be about 14 million in a few years the caregiver burden is enormous that goes along with this uh the costs are even more than taking care of a patient with cancer or heart disease uh and this is an epidemic really um and globally it's you know literally a hundred hundreds of millions of people are going to be affected by this now you've been on the forefront of alzheimer's research um and you've seen amazing results in helping people prevent dementia through various protocols that are based on functional medicine and your wife is a functional medicine doctor and and introduced you this many years ago and and you you know you often tell the story how you came across my book the ultramine solution which i wrote about 12 years ago that mapped out how we can start to think about treating the system not just the brain itself and you created the bredesen protocol uh that fundamentally changes how we think about cognitive decline so tell us about we know how you came to understand that what you learned as a neurologist and as a researcher around alzheimer's corresponded with these emerging ideas around functional medicine and how that led to you develop the predestined protocol yeah you know and thank goodness there was functional medicine or we would still be you know figuring out how do we put all this together so you know we were interested for 30 years in the laboratory and we're simply going and as you said people have been unable to treat these diseases alzheimer's frontal temporal dementia als neurodegenerative disease has been the area of greatest biomedical therapeutic failure so we were trying to study what are the molecular drivers of this process and what we could see with research was that there is a central switch app which is literally integrating over all these signals so the big surprise was that everybody was talking about alzheimer's had the wrong idea they've told you it's misfolded proteins it's reactive oxygen species you know it's prions it's all this stuff but the reality is when you look at it at the heart of alzheimer's is an insufficiency you have an insufficiency of signaling which is picked up by this molecule app which then is protecting your brain for downsizing it's very much by the way what's happened with covet 19. we have an insult sarsko v2 and of course we're supposed to be uh sheltering in place and social distancing but what's happened with that with less interaction we have a recession this is exactly what goes on in the brain of an alzheimer's patient you have insults and these are everything from herpes simplex type one p gingivalis from your mouth various molds from your sinuses leaky gut as you know on and on and on dozens and dozens of these things and these insults trigger your brain to say okay i need to downsize i need to shelter in place literally and it produces something that is an antimicrobial which is the amyloid so as long as you don't find those things and correct them you're going to keep downsizing downsizing until you can't dress yourself you can't speak and unfortunately when you go in to see some doctor and expert in alzheimer's they don't look for those things and this is a critical piece so what we studied was what is the fundamental nature of this problem and the nature of it it is an insufficiency in the network that mediates plasticity and so what happens you lose that plasticity and you start downsizing just as what is plasticity what is plasticity so plasticity is the ability to change you know from plastics and the greek something that that is moldable so the ability to mold your brain to add new thoughts to add new memories this is exactly what is lost in this disease because that is the network that is now downsized it's basically saying okay mark can you live with ace with a fewer synapses so that we can fight these things you're you're going to use your resources now to fight the various pathogens or toxins or you know changes in insulin sensitivity and things like that but you're going to have to live with a smaller function basically just as we are stuck with with the recession here in the united states right now yeah so your neuroplasticity is essentially all the networks that tie everything together in your brain all the connections between the cells all the messaging all the new wiring that helps you learn and grow that diminishes with all these insults that cause your brain to as you say downsize yeah it is protecting itself and what we've always learned is that once you go down you're not going back up that once you lose your memory it ain't coming back and that the best we can do is maybe slow it down and the best research uh we're talking about billions of dollars hundreds of studies over many decades have really come up with a big fat zero when it comes to any meaningful result to stop to slow or to treat alzheimer's or dementia and and uh we we've spent so much money and got so little because we've been focusing on the wrong thing so in your program the end of alzheimer's program you talk about what we actually should be focusing on and you talk about these metabolic factors that can literally trigger this downsizing so what are those factors and and how do we rebalance them so we don't end up having this decline in brain function yeah it's a great point and so if you know you can actually see people improve just as you described in your 2007 book uh and so this shows that there is a set of things that are synaptoblastic making connections and keeping connections and a set of things that are synaptoclastic pulling back and when you're young there's this beautiful balance you know you're actively forgetting the seventh song that played on the radio and the work yesterday and stuff that sort of thing but then what happens with everybody with alzheimer's too high on the synaptoclastic too low on the synaptoblastic side so what are the things that are synaptoblastic well step one we there is an energy gap this turns out to be one of the most important parts about the alzheimer's brain as you know if you just look at a pet scan an fdg pet scan you see that there is a decrease in the utilization of glucose by your temporal lobe and your parietal lobe that is the hallmark the signature of alzheimer's disease and it's present for about 10 years before a diagnosis so you have a critical energy gap that you need to change you need to address that gap and the best way to do it of course is with ketosis and you can you know stephen kinnain showed years ago you can ramp those ketones up to one two three millimolar beta hydroxybutyrate and you can you can address that energy gap that's the first thing the second thing is when we used to grow the neurons basically using a ketogenic diet you can increase the way the brain uses energy and make it basically have more energy by feeding it fat instead of sugar and carbs exactly and there are two problems there one is that you've lost the flexibility you've lost the ability everyone's stuck on the glucose side they're not able to use the ketone side you have to have the flexibility and then the second is that they have the insulin resistance so that even though they're trying to use the glucose which is what they've used for years and years and years because of the standard american diet they're now unable to do that because you literally have changes in the ability of insulin to signal you change your insulin signaling irs-1 molecule from tyrosine phosphorylation which is active to serine and threonine phosphorylation which is inactive you literally shut it down and when we used to grow neurons in a dish you know what you're saying is that sugar kind of screws up your brain's ability to metabolize energy is that what you're saying as that's exactly right okay because i don't people know what tyrosine and serine is i think that's a basic take-home point is that when you eat sugar your brain doesn't like it and it starts to shut down and it leads to alzheimer's it it becomes resistant to it exactly right the resistant to the insulin effects which are so critical for keeping your neurons alive so the beautiful thing here is that what we saw in the lab reflected beautifully what you and david perlmutter and jeffrey bland were saying clinically so that the you know if we hadn't had all the great work you did we would have been stuck say okay what's the next step we take now from the lab but here's this beautiful functional medicine all ready to plug in the underlying science of alzheimer's disease so in that sense very helpful and as you said very you that you sugar damages your ability to support your synapses so you've got to address with ketones you've got to address the energy you've got to adjust the insulin sensitivity got to get insulin sensitive instead of insulin resistant which virtually everybody with alzheimer's is and then you have to have you have to reduce any inflammation your brain responds to inflammation by saying i am being attacked there's some organism out there so i'm going to make this amyloid which kills these microorganisms but in so doing i again i'm downsizing so you've got to get rid of that inflammation not just get rid of the inflammation resolve it but you also have to find out what's causing it and address that so those are the first three things and then you've got to have the support you've got to have hormones and trophic factors and nutrients that are critical for rebuilding those synapses fortunately before you actually lose the neurons you first lose the efficiency of the synapses the synapses don't work well but they're still in place thankfully so when we do the right things these start working well again yeah you know it's interesting i remember reading this article because what you're talking about is is multiple different factors that explain the phenomena we see as dementia but that it's not one disease and it's many diseases and many dysfunctions manifesting as a particular set of symptoms that are common among people but it doesn't tell you why so everybody you look at who's got cognitive decline or alzheimer's you have to be a detective and find out what is their particular issue is it more in some resistance is it more of an infection is it a mold is it a toxin is it some other nutritional deficiency or hormonal lack like too much of something not enough for something else and what's really uh striking is that the inflammation is this common theme in all brain dysfunction whether it's depression or add or autism or alzheimer's or parkinson's or whatever it's inflammation in the brain that's a lot of your work has really been in understanding what is driving that inflammation because the amyloid like you said is not the problem it's actually your body's attempt to fix the problem it's the band-aid that the body uses and to deal with the inflammation and the microbial factors which often can come from gut and other factors so talk to us about how you know we need to rethink this because i i remember reading this article years ago in jama which was called shifting thinking about dementia and there was a great lie in there that says we combine uh categorical misclassification with ideologic imprecision and what that means in english is that we we categorize people according to symptoms not causes right and we are not really good at finding the etiology or the cause right so we're kind of just like throwing you know spaghetti at the wall trying to see what works and what you've done with the bredison protocol and the end of alzheimer's program is to really map out systematically the ways in which you can identify those factors that are harming your brain right we call you call them dementogens right right and and what are those factors that we need to provide the body to optimize and enhance brain function right exactly so you know what's what happens in covet 19 again is cytokines and so you know cytokines are killing people as you know the cytokine storm is the problem well part of the inflammatory cascade part of your innate immune system activation is amyloid so we have to quit thinking of amyloid as the cause of alzheimer's amyloid is just like cytokine storm except it's longer of course kova 19 has compressed all the things that go wrong in alzheimer's into two weeks instead of 20 years but it's the same idea as long as you have something that is saying hey something's wrong with your brain you are going to continue to make that amyloid that's part of the response so you're absolutely right you have to determine what these factors are and it's often there are often biotoxins or organic toxins or metallotoxins air pollution of course has turned out to be a big one so all of these critical things and then various pathogens and there are several of these chronic pathogens from babiesia to bartonella to borrelia to various mold species uh to herpes simplex type 1 to hhv-6a these are all chronic pathogens and typically as you know we don't know that we have them so as you said you know this is interesting to me that the we used to talk about people dying of fever you know in the 1600s people died of fever all the time and so now people talk about people dying of alzheimer's it's no different than fever you shouldn't have a period after fever and be fevered due to what and you shouldn't put a period after alzheimer's alzheimer's due to what that's the critical piece and so the doctors have always put the peer they say you have alzheimer's but we need to know why for each person and it's not one thing it's not like tuberculosis it's always the tubercle bacillus right it's all these different things so that's it is a systems disease that's the point yeah it's so true you know i think uh in you know in in uh neurology there's a famous uh joke that the the you see the doctor and it's basically diagnosed and adios here's the name for the condition you have and there's not much we can do about it goodbye get your life in order yeah and that makes me crazy because you know over 25 years of doing this and working with people's brains i wrote about this 12 years ago i've seen more and more since then of how we can really impact these patients i mean i i saw a patient who had uh dementia she had lewy body dementia which is sort of a sort of combo of alzheimer's and and parkinson's she couldn't walk she was in a wheelchair uh she had real cognitive issues she was trying to run her business she couldn't function anymore and we we essentially did this detective work that you're talking about using the approach that's described in the end of alzheimer's program in the bredesen protocol and we found she had tremendous gut issues tremendous overgrowth of bacteria in eastern her gut massive nutritional deficiency she was diabetic poorly controlled her thyroid wasn't working she was post-menopausal and all these various issues and we simply corrected those things that we found and she came back incredibly and her energy came back her cognitive function came back she'll be in her business again she was able to she was a relatively famous person able to record another album and write songs and write a book and where she'd been totally dysfunctional and non-functional before and was able to even get up out of her wheelchair and start walking so it's quite remarkable this was even over 80 years old so no matter where you are in the spectrum we see these remarkable changes that people just don't think are possible and when you talk to traditional doctors about it they kind of dismiss it but you know there has been research on this you know one one of our colleagues and you published a number of papers uh looking at these case studies but one of our colleagues richard isaacson did an incredible study that looked at uh similar kind of personalized interventions not even the full protocol and saw that he could not only stop but he could slow it and he could also reverse some of the symptoms of cognitive decline so can you can you talk a little bit more about you know what what kind of approaches you do to looking at the factors that are going on and maybe sort of list some of the key factors that you're finding that are common uh among among these patients yeah and i think the best way to do that is to talk about the subtypes so what we described back into published back in 2015 is when you start to look at these to do the very evaluation that you just talked about then in fact what you find is that there are people although there are multiple contributors people tend to have specific subtypes so type 1 inflammatory these are people who have exposure they may have leaky gut they may have periodontitis they may have metabolic syndrome lots of reasons that they have inflammation and that's the critical driver and you can literally follow the molecular pathway from nf kappa b activation part of the inflammatory pathway to where it's producing the amyloid which as i mentioned is part of the inflammatory pathway so that's the type one in those people you need to look for things like hscrp tnf alpha things like that and then you need to use resolvins to improve these and then you need to identify where this is coming from and attack that so getting again upstream is critical then there's type 2 which is atrophic and these are the people where they have low vitamin d pregnenolone progesterone estradiol testosterone you know on and on the critical supports for this nerve growth factor brain derived neurotrophic factor b12 all these things it takes as you know it takes a lot to keep a brain functional you have over 500 trillion synapses in your head you've got an amazing super computer inside your skull so you've got to keep that supported and you know prevent it from downsizing again this is a disease of insufficiency and by the way one of the most common things we're seeing now nocturnal hypoxia people don't realize it the doctors don't check it they say oh i don't snore i don't need to look at this and it turns out that when you actually look at it you see that the oxygen has crept down during the night into the 80s even into the 70s we see people in the low seventies who don't realize that they have problems with oxygenation sleep apnea you mean sleep apnea it's it's often without sleep that's the key some of the sleep apnea is the tip of the iceberg but there's upper airway resistance syndrome as another one of these and there are people who just don't get enough oxygen at night even though they don't have full-blown sleep apnea so that's critical to check and then of course we talked about the ketones earlier then there's the type 1.5 which is glycotoxic and this is the people where they've got both inflamma inflammatory changes because of glycation of hundreds of proteins and they've also got the atrophic effect because they now have resistance to the insulin so that's type 1.5 are glycotoxic those are the factors you got to look at their hemoglobin a1c their home ir stuff like that and glycotoxic means sugar being toxic to the brain that it forms these crusts sort of like a creme brulee on the top of your brain so it can't really work properly and that you talk about atrophic which means lack of things to help the brain grow trophic factors are essentially the fuel or the food or the ingredients that the brain needs to function including hormones and the right nutrients and vitamins and and fish oil all kinds of stuff that the brain actually needs to function yeah so so you you talk about the way you identify this and i thought this was brilliant the first time i heard about it you know everybody knows they should get a colonoscopy to check their colon but you come up with this term called a cognoscopy which i love which is essentially how do you do a deep dive into your brain and all the things that affect your brain that cause risk of cognitive issues and by the way all the things you measure with a cognoscopy are all the things measure for any chronic illness to look at and some are more prevalent different illnesses but with alzheimer's you really come up with a model of a cognoscopy so can you talk about what is a cognoscopy what should we be looking for how do we get it can we get it with a regular doctor or is this something that you really need specialized care for yeah it's a great point and people have told me don't use that term cognoscopy it sounds so horrible but it's simple it's easy to remember and we all know we should get a colonoscopy we turn 50. so we recommend everybody 45 or over get a cognoscopy and as you said it is things related to chronic illness but the key is to prioritize i mean that's the key the people who are getting the best results as you know are the ones who are prioritizing the things that are the most important drivers it's different for each person for some person you know it's going to be getting at that barely every other person that's going to be getting at that mycotoxin and another person is going to be the glycotoxicity so today it's very simple to get one might be mold one might be lime one might be sugar right or whatever it might be mercury might be mercury right and might be vascular a common one is people just don't have the vascular support for their brain and this is why they are downsizing and so if we return that support we return the oxygenation and the blood flow they do better hey everybody it's dr hyman thanks for tuning into the doctor's pharmacy i hope you're loving this podcast it's one of my favorite things to do and introducing all the experts that i know and i love and that i've learned so much from and i want to tell you about something else i'm doing which is called mark's picks it's my weekly newsletter and in it i share my favorite stuff from foods to supplements to gadgets to tools to enhance your health it's all the cool stuff that i use and that my team uses to optimize and enhance our health and i'd love you to sign up for the weekly newsletter i'll only send it to you once a week on fridays nothing else i promise and all you have to do is go to dr hyman.comforwardslash picks to sign up that's drhyman.com forward slash picks p-i-c-k-s and sign up for the newsletter and i'll share with you my favorite stuff that i use to enhance my health and get healthier and better and live younger longer now back to this week's episode so the way you can get a cognoscope it is three things it is number one a set of blood and urine tests easy to do number two it is a simple online cognitive assessment and if you're completely asymptomatic and doing great and you're just in for prevention you can stop there just those two things if you have any symptoms or you're not scoring well on the cognitive tests you want to include number three which is an mri with volumetrics you want to know the volume of your hippocampus you want to know the volumes of your frontal lobes and your parietal lobes and things like that and hippocampus is that little memory center in the brain tends to shrink right and i've heard you present some cases that when you've done these cognoscopies you start these interventions that are in the end of alzheimer's program your new book which everybody should get and you map out the changes over time when you implement the bredison protocol and the remember the story you told of the neurologist the neuroradiologist who looked at the scans and was like this was before and this is after this is doesn't make any sense i've never seen this in my entire life to go from like 20 of what it should be to 70 or 80 or 90 of what it should be can you explain how that happens absolutely and you know we see this again and again and again we're actually just publishing another paper showing not only increase in hippocampal volume but also improvement in pet scans where you go from a pet scan that shows alzheimer's to a pet scan that doesn't show alzheimer's we also see improvements in electrophysiology so improvements in eeg improvements in evoked responses and of course improvements repeatedly in cognitive scoring and testing so this is happening because you are putting the things in that actually support the brain you're getting hormones and trophic factors that are critical so the brain is now making the synapses once again now we don't know yet is it making more neurons is it making just more synapses is it changing in terms of its astrogliosis we don't yet know what's happening at the cellular level but we do know that that atrophy is improving in many of these people so so you said two things there that sort of struck me one is that your brain can grow you can rebuild brain tissue that's been damaged by the insults and literally grow your memory center which correlates with improved cognitive function on the the brain cognitive testing and second you said you can do a brain scan that you can see alzheimer's on you can repeat the brain scan and the alzheimer's markers on the brain scan are gone like that that's like what stop presses headline news why isn't this on the cover of new england journal jama cover of new york times wall street journal what's going on here yeah well partly because of course the standard is you know do a thousand people and then do the whole study so you know at the beginning you have to you have to start somewhere you know with just getting the airplane off the ground you've got to start somewhere so we're looking as you said at these various cases we are in the midst i should say of the you know the first trial in history in which we look at all the different contributors for each person and do all address all these different things we'll be finished with that in december so very enthusiastic about that trial but yes we do see in these you know anecdotes that we're now looking at we see improvements in pet scanning and electrophysiology and hippocampal volume and all these things when you are getting these people to improve and to do the right things you're literally just restoring a synaptoblastic neurochemistry and what that means is you're creating a brain that likes to build new brain cells that is not that is capable i know it's over almost 30 years ago it was discovered it was of course i was taught years and years ago that you know the brain doesn't make new neurons you get the ones you have and that's it and then about 30 years ago it became clear that hey there are neural stem cells and you actually do make new neurons throughout life and so it's a question of which ones do you keep and do you have do you have them interact with other neurons do they become part of the functional network so it turns out you do make more of them and if you do the right things you can keep them and you can keep their interactions now one of the big topics that you cover is the microbiome leaky gut inflammation alzheimer's and so most neurologists aren't saying well let me look at your digestive system let me look at your gut and seeing if there's inflammation there and how does that connect to the brain and you know we've talked to a colleague of ours rudy tansy who's been pioneering some of the work around finding microbes in the brain we thought the brain was sterile we thought the brain had a blood-brain barrier that prevented anything bad from getting in well it turns out that barrier is only semi-permeable and that things can get in and and they can be even microbes so can you talk about this amazing new research on the gut and the brain and the microbiome and how that impacts what we have to do with patients with alzheimer's and by the way that that patient that i had who had really had brain dysfunction her main issue was her gut and we fixed it up after decades of being constipated needing enemas to go to the bathroom and laxatives and tons of bad bugs growing in there it was just amazing what happened we fixed all of that absolutely and i think that you know when a neurologist makes a diagnosis of alzheimer's or pre-alzheimer's the best thing the neurologist can do is refer the patient to a functional medicine doctor to deal with all the things that are driving this problem but of course the neurologists have felt like oh this is our province you know we have to give the drug and watch you go downhill which is really unfortunate i think that's going to change so absolutely uh the you know the gut is a driver and i think one of the most interesting studies that was done in the last couple of years was a group they were actually studying rodents but what they were doing was injecting candida and they thought they wanted to see how long does the blood-brain barrier keep the canada they injected it into the blood vessels and asked okay what happens when it goes by the brain how long can the brain keep it out and the answer was it went in immediately so there is yeah canada and this is in a normal animal so the fact of the matter is there is much more communication just as you pointed out and as rudy has been pointing out there is much more communication between the brain and the periphery than anyone thought possible and what have the pathologist shown us when they look in the brains of patients with alzheimer's what do they see herpes simplex in the brain they see candida in the brain they see borrelia in the brain they see p gingivalis from your dentition in the brain all these different gum disease so the bottom line is our brains are communicating with the periphery much more than anyone thought before and as you said we actually probably have a normal brain might as much as that kind of blows my mind we we actually probably do have a normal brain microbiome and we're going to have to have probiotics for our brain at some point cognobiotics right cognobiotics yeah there we go uh wow that's incredible well you know the the approach also that is needed is something we don't do in traditional medicine which is how do you restore a healthy microbiome right and this is what the focus of functional medicine is how do you take the symptoms that people have or even they may not have any symptoms in the gut but look at the environment in there and optimize it by taking up the best of putting in the good stuff and using the functional medicine approach to really heal the gut so i think what you're saying is it is that each patient is different and and some may have got issues some have other issues you know one of the other issues that really affects people is heavy metals and and there's been a lot of talk in the past about aluminum and alzheimer's but it was sort of you know sort of ignored and and i remember a patient i had one of the first patients that i was like i don't know what i'm doing with alzheimer's this patient's being diagnosed with alzheimer's dementia um i have no clue if anything i'm going to do is going to work but i'm going to try my basic framework of functional medicine to see if we can just take out the bad stuff and put in the good stuff so i did a cognoscopy of sorts yeah got rid of the dementogens and what was really striking about this guy dale was he was seven years old he was a form ceo of his major family business couldn't function at all sort of was in the corner basically depressed and not functioning nobody want to be around him and he had pretty significant dementia um but when i looked at his story he grew up in pittsburgh and he lived in pittsburgh and there's steel plants there and almost every patient of mine from pittsburgh is mercury toxic because they put coal ash on the streets they put it on the fields gets in the food it's in the air and he had a mouthful of fillings and normally you know normally when you do a challenge test for mercury with a patient in functional medicine you know you see a level of 20 or 50 that's like you worry about that it's high yeah um a hundred you know i've had you know maybe 20 in my whole life of doing pay me 10 to 20 000 tests his was 350. i never seen anything like that yeah one other patient i think i had 400 but almost nobody liked that and and i got rid of his fillings we detoxed him from the mercury he also had all these genes like apoel4 he had methylation gene problems it has to be vitamins he had genes that affect insulin resistance he had years of gut issues he had iron irritable for decades and was on stellazine for his gut uh and so he had all these all these issues that we treated so we fixed his insulin and blood sugar we fixed his gut we fixed his b vitamins we got rid of the mercury and the guy literally came back like rip van winkle from the dead and it was the most striking thing i'd ever seen in my life i'm like holy cow like i just cured alzheimer's yeah and i'm like and this was like 15 years ago and i'm like what and and that was really began the process of me going wait a minute the brain is so fixable if we understand the insults which you have mapped out so well in the end of alzheimer's and if we understand how to actually repair and heal the system so talk about mercury in the metals and how these affect the brain because this is a this is not to say that everybody with alzheimer's has heavy metals so they don't but i've added a number of patients that makes a huge difference when you deal with it yeah but as you said you know a certain number of them that is the key piece and here's the thing you know i mentioned earlier your brain makes amyloid when it is under attack by microbes because it's trying to kill the microbes but interestingly the gene itself that amyloid comes from which is called amyloid precursor protein is a gene that is responsive to metals so there's literally a metal binding region on the rna this piece that's going to be making the protein so it is it responds to mercury it responds to copper zinc iron so this thing is part of what's binding up those metals so it actually binds up so what happens is you can actually give mercury and as you indicated mercury is literally a cause of alzheimer's not in everybody but in a small group of people probably something like three to five percent of all alzheimer's patients which still it's a lot of them there are going to be 45 million people with it who are the currently living americans 45 million of us will develop alzheimer's during our lifetimes five percent is a couple of million people have mental issues exactly this is a big problem so you this is why as you said you want to check this on everybody because if that's one of the contributors you need to deal with it and when you do they do better and it does it increases the production of the amyloid and it both interestingly it induces the amyloid and it induces the tau as well so it is a great way if you want to give yourself alzheimer's take some mercury eat some sushi exactly but the funny thing is you know that not everybody accumulates the mercury and it's a lot has to do with genetic variation i personally had mercury toxicity and i had cognitive dysfunction i felt like i had dementia really i did my level wasn't 350 it was 187 which is bad enough still yeah and still bad enough and so i i understand from a personal point of view what this does and it's one of the most potent toxins on the planet probably second only to plutonium it is the most potent neurotoxin and and it's just it's unconscionable to me that we don't as a profession really think about the role of toxins we check the blood levels but that doesn't really reflect the total body burden of these metals and so there are ways through functional medicine and the approach you're talking about to really do this let's talk about um the next topic which is you know hormones and i think uh you know i've seen some really interesting responses to hormones around thyroid sex hormones this is what we call a trophic factor so it's not something that's hurting you it's something that you're lacking that your brain needs to function so talk about some of the big hormonal findings and what you're seeing with these patients yeah and there's some elegant work published out of the mayo clinic a number of years ago where they simply looked at women who had oophorectomies for whatever reason picked their ovaries out they take their own movement of the ovaries right at the age of 40 or younger who did not get bhrt versus one would not get hormone replacement versus those who did get hormone replacement and even though the hormone replacement has been imperfect for many of these there was a striking difference the ones who did not get the hormone replacement had a more than doubling of the risk for developing alzheimer's even though the alzheimer's wasn't diagnosed till years later goes perfectly with the science that we talked about earlier this app is looking for support and when it does not get that support it's flipping over to the synaptoclastic it's saying we can't support this brain and it goes beyond just estradiol to progesterone and pregnenolone and testosterone and vitamin d and all these things thyroid hormone as well these are all critical and so repeatedly people have come upon the fact that you're getting this at the time often when you're losing those hormones or down the road from this and we see a lot of people now uh something i never saw when i was training people who are in their 50s women who are going through menopause or perimenopause who have their first symptoms at that time so for a number of reasons it's huge not only the support side but also as dr chris shade has pointed out progesterone is one of the most critical parts for your detoxification apparatus so when you now get this relative lowering of so-called you know relative estradiol excess or estrogen excess this is because you've lost both but you've lost the progesterone to a greater extent you are at increased risk for toxin-related alzheimer's disease and you're now getting this synaptoclastic burst you are re-releasing these toxins including mercury that you have sequestered for so many years so by multiple mechanisms having too low a support from your hormones is a critical risk factor for cognitive decline yeah and there is controversy about hormone replacement particularly on cancer and yeah do you worry about that do absolutely and so i think it's critical to have people see experts in this area you know dr anne hathaway dr you know prudence hall and many people who are bhrt experts uh who look at you know when's the best time to do this what are the best doses where you know when if you can you improve get you get the better outcome then it was worrying yeah there is a worry about cancer although some of the studies have actually shown reduced with appropriate use of estrogen and progesterone reduced likelihood of cancer so you you know you really want to stack those against each other and there's very personalized approaches to this depending on your genetics your family history uh you know what what actually is going on with you what your biology is and actually helping women to personalize the treatment using the biological hormone replacement uh not absolutely actually the kind that comes from horse urine which is what a lot of the studies were done so we don't even have big studies on the good stuff all right let's talk about uh nutrition um yeah we're going to talk about diet a little bit but i want to i want to talk about the widespread nutritional deficiencies that you're seeing and how those play a role in the brain and cognitive decline and what are the most important nutrients we need to be focusing on yeah you know it's amazing to me because we've got so many things working against us and obviously you've written probably more on this than anyone looking at the critical nature of nutrients for your health you know looking at all you know changing the world one bite at a time and all these fantastic things that you've done and this fits again it's it just fits perfectly with the science that we've studied over the years and so you know paul clayton from oxford has pointed out that we don't even have the nutrients in the soils that people had 100 years ago 200 years ago when we were thinking you know these people while they didn't know what they were doing they were doing much better than we are because they actually he's pointing out that you know henry viii had better nutrition than we do uh of course he ended up being obese and had problems with arthritis and things but the key is that they actually had better soil so we've got essentially a triple whammy number one we have poor soils and therefore we have poor overall nutrition number two we're eating food that's way too high in sugar obviously and way too high in processed foods and all these issues so we're eating stuff that's that's toxic and then number three we're we're not getting enough nearly enough fiber nearly enough phytonutrients so we have this system it's as if you took your car out you're trying to drive this car that needs appropriate fuel and you're putting stuff in that is very low octane it's just sputtering it's spluttering it's having trouble getting out of the block it's just you know you might go a little way your mic and that's what we're all dealing with every day so if you crappy fuel crappy fuel you optimize those things you get people into some ketosis you get them appropriate fiber for for detox and for their microbiome you get them appropriate low carb diet you do you get the appropriate night of phytonutrients and by the way one of the most common deficiencies choline as you know choline is needed to make acetylcholine which is a critical neurotransmitter for memory and it's reduced in people with alzheimer's and i've checked myself on chronometer and i realize i'm not getting enough choline in my diet you know we should be getting around 550 milligrams or so of choline each day which you'll get from eggs and you get eggs and from yes from sardines from liver obviously you know organ meats things like that uh from oysters things like that a number of vegetables as well or you can if you're not getting it from there take some cytocholine this is why professor wortman from mit found that cytocholine is so helpful for synapse formation yeah so lots of ways to get choline but please make sure that you get enough so all of these things are critical so what besides choline is so important for the brain oh well nutrients what nutrients take i'll take flavonols flavonols and flavonoids those alone study that just came out showing that over thousands of people those who were in the highest quartile of flavanols had a much lower dementia risk than those who were in the lowest quartile of flavanols so things like strawberries and things like grapes and things like that all all helpful to give you the flavonols and then the flavonoids things like blueberries and things like that all critical so those are like 25 000 different phytochemicals and exactly and flavanols and flavonoids are part of those and so eating a rainbow colored diet where half your plate is vegetables is a simple take home to protect your brain and pretty much everything else that could go wrong with you so we've got choline we've got flavonoids and phytonutrients what other major nutrients are an issue well you know the minerals so the key ones that almost all of us are deficient as you know in zinc and and zinc has become a huge issue because of copper 19. so many of the people who are deficient in zinc are reduced and have an increased poor outcome increased risk for having a poor outcome from cova 19. so zinc magnesium iodine potassium those are the big four that most of us are deficient in and then of course vitamin d as you know the study that just came out about 10 days ago showing if you take the people who are low in vitamin d they have a much worse outcome in covid19 than the people who have sufficient vitamin d and of course alzheimer's is no different the same thing you see people who are low in vitamin d more likely to get alzheimer's people who are sufficient vitamin d and of course same thing in multiple sclerosis high vitamin d associated with better outcomes so as you said it's multiple diseases that all depend on these critical factors some of the most important things i found are b vitamins i once had a patient who was about 80 something years old she was on multiple boys very successful woman but was noticing depression and really severe cognitive decline he'd been diagnosed with mci or pre-dementia told to get her affairs in order she came to see me and i'm like checked her levels uh and found she had a really high level of something called methylmalonic acid and homocysteine which are things that most doctors don't check but reflect your status of b12 which is methamonic acid and homocysteine which is the foley and even b6 so i basically gave her b12 shots high doses of methyl folate which is a particular kind saw she had some jeans that made her need a special kind of foley and she called me back and was doing amazing and all of her symptoms had gone away and then a few years later maybe four or five years later she called me up and i thought oh i saw my schedule like maybe she's not doing well or she's declining i kind of worry about her a little bit and and she's like dr hyman you know i'm going trekking in bhutan and i want to know what i should do to prepare and what i should be taking with me so i was like okay and i think you know sometimes it's that simple but it's not always that simple but i think understanding the role of nutrients and nutritional deficiencies is huge uh it's far more common than we think you can't get everything you need from food i think a lot of the reason the studies on vitamins have failed in mars trials whether it's for cancer or heart disease is because they're not dealing with the the whole system they're just like if you're eating you know donuts all day you can take all the fish oil or vitamin d you want it's not going to do anything to fix your risk of heart disease right so you have to look at everything together so absolutely so let's talk about uh this this concept you talked about called keto flex we've touched on it a number of times but what is the diet that's best for your brain and what is the diet that's best for your brain if you actually have alzheimer's yeah great point so let me preface this by saying i know far less about nutrition than you do so you know i'm really talking to someone who's an expert here i i'm looking at the neurochemistry so i'm interested in you know synapses how they're made how do you keep them and so this is keto flex 12 3 is nothing more than what's the thing we can use to drive your biochemistry toward an optimal biochemistry for making and keeping synapses and so what do you need you need to have ketosis you need to have all the nutrients we were just talking about for support you need to have high fiber because you need to help yourself detox you need to improve your microbiome all those sorts of things you need to have appropriate probiotics to support your microbiome and you need to have fasting periods for autophagy fasting periods for helping you to get into ketosis fasting periods for all the great things that fasting does even in things like lowering your blood pressure hypertension is another big risk factor for alzheimer's so if you put all that biochemistry together and you mix it up you know mix it up in a blender and you say what's the diet we named it keto flex 12-3 it's ketotic it's mildly cataract it's plant-rich this is not a bacon-related keto ketotic diet ketogenic diet this is a plant-rich high good fats intermediate proteins low carb and no simple carbs it is flexitarian and i realize flexitarian means you have to eat some meat and fish it's really more about flexibility you want to be a vegetarian no problem make sure to check your homocysteine and your vitamin d and things like that but fine if you want to have some meat you know have some fish it's hard to be i think keto if you're not eating animal protein i mean you can do it as a vegan a vegetarian but it's harder because you smarter hard to eat reduce the carbohydrate load because you need the protein from beans and grains and things like that so how do you do that with those patients yeah that's a great point and so you know again because getting into ketosis is so critical for supporting brain energetics we tell them just start by taking some exogenous ketones do it for a couple of months no problem because we need to get that energy up past it as a supplement exactly then you can get yourself into endogenous ketosis and we do that by increasing the fat consumption but you know all the appropriate oils and the nuts and the seeds and all the things you've written about that are excellent sources of good dietary fats and then again and then if they can't get into enough ketosis okay we can supplement that a little bit to get them where they need to be so it's then so that's the flex part and then 12 3 is 12 hours as a minimum and if you're apoe4 positive you should really make it 14 to 16 hours of a fast between when you finish your dinner when you start your breakfast brunch or lunch and then the three is for three hours before go you go to bed you don't want to be eating right before bed because it'll spike your insulin reduce your you know your growth hormone and your in your melatonin and so forth and so on so this is why keto flex 12 3 is essentially our attempt to take the neurochemistry of synaptogenesis and to put it into a diet that's so incredible so you're saying you don't have to be keto if you're not having alzheimer's for prevention this is more for for treating a patient right it's a great point and this is one of the things we've been arguing about lately um if you're just there for prevention do you want to get yourself into ketosis it depends on how concerned you are if you are really concerned about prevention then you probably want to do get at least part time getting yourself into some mild ketosis but you're right you don't have to for someone who's trying to reverse absolutely it doesn't reverse well if you don't get into ketosis because you're missing that energy gap and i yeah i've seen i've seen that with my patients when i when i put them on ketosis if they're struggling because often people get better without it but you know it's not a low glycemic diet but then you really want to push that envelope they seem to do a lot better um and what about apoe4 because this is a common gene that increases your risk and you have one or two copies and there may be some interesting data that i'd love to explore with you because historically there was concern that these patients should not eat saturated fat they may have more problems with cardiovascular disease and dementia right what is the current status of the data on these apoe4 patients um which are a lot i mean they're what about 45 million or something in america yes 75 million yes so here's the thing three quarters of the population is apoe4 negative uh and one quarter of the population is apoe4 positive so it's incredibly common and there are some advantages you have to have into being apoe4 positive and so in third world countries it actually gives you a big advantage because you have a more pro-inflammatory state you're better at fighting off pathogens and you're actually better if you have a starvation diet if you're starving you want to be apoe4 positive because you're a better fat absorber so 75 million americans have one copy and they are at 30 percent lifetime risk for alzheimer's if you're negative about nine percent lifetime risk one copy thirty percent two copies well over fifty percent most likely you will develop alzheimer's and that's seven million americans so critical for all these people to be on prevention absolutely and as far as the fats it's a good point and this is a controversial area still some arguments would say yes a limited amount of saturated fats okay i think most people who are apoe4 positive would like to stick with the monounsaturates and polyunsaturates and stay away so typically we don't recommend for example coconut oil mct oil we recommend if you want to take someone to get into ketosis exogenously just take some exogenous ketones take ketone salts take ketone esters those sorts of things you can do that a couple of times a day and get nice spikes in your ketone levels and then ultimately again you want to get into it endogenously so you know if i had to to say one way or the other today i would say the preponderance of the evidence today is on the notion that you would want to stay away from saturated fats having said that there are people who do have some saturated fats in their diet and have beautiful lipid profiles despite the fact that they are apoe4 positive so you want to check your blood work and see how they're responding in your diet not just gas right absolutely check your ldl particle number try to keep that between 800 and 1200 or if you want check your calcium score to make sure that you don't have any cardiovascular disease of course there's an increased risk for cardiovascular disease as well with people who are apoe4 positive so as you said check to see where you stand to make sure you're doing well now a lot of people listening and if there are medical professionals listening they probably think it's heresy to say that we can reverse alzheimer's that it's providing false hope that we don't have the science behind it uh and it's really not possible uh but you and i both seen that it is possible uh and it's not always a hundred percent but the question is you know really to what degree in your experience is this is this reversible and and and how far along um can you be before you can you know be confident that's going to be reversed otherwise is there a time when it's too late um so can you talk about what that is maybe a case or two that explains you know really how this works in in practice absolutely so we can think of this in four phases phase one is where people are asymptomatic but they already have the pathophysiology ongoing and those people the ones for for prevention and they do very well let me ask you a question have you ever had a person who came to you for alzheimer's prevention who then developed alzheimer's while on your program um i think i've had people you know progress slowly over 10 years you know like i've had people kept them good for 10 years and then and as soon as they if they slip off the program that's when they get into trouble well exactly slipping off the program so i asked this to you know many functional doctors typically very few people have seen this when you're on prevention and you start when you're asymptomatic you do very well then the next phase is sci subjective cognitive impairment which actually lasts about 10 years where you know there's something wrong often your spouse does but you're still scoring well on the testing those people virtually all of them get better because it's these are still early stages then the next stage is mild cognitive impairment and these are people who are scoring 23 24 25 on the moca scores or 26 this is montreal cognitive assessment scores out of memory 30. yeah so they clearly have significant early alzheimer's but we call it mild cognitive impairment at that point and the majority of those people will increase their scores and we wrote a paper on this with a hundred documented improvements and published it in 2018 with 15 different laboratories and the average improvement in score was 4.9 so if you came in at 22 you ended up around 27 typically so that's clearly improving and they typically sustain it then the ones who then are all the way to alzheimer's they're now losing activities of daily living you know calling someone alzheimer's is like saying late stage cancer metastatic cancer because it's a very late stage of this process that's been going on typically for 20 years some of those people improve and and we've had people with moca scores of zero improve but when they improve they go from zero to five you know they'll they dress themselves again they speak again they interact with their families again they can even do emails again but they're not normal so we're not so far not able to take someone from zero to 30 and that's one of the big research questions right now what is missing they come to a next plateau what do we need to get them to a higher plateau is there a rate limiting step that's preventing or is it just the massive loss of synapses do we need to then think about stem cells intranasal trophic factors yeah methylene blue all these sorts of things that are coming ewot that's another thing we've been interested in exercise with oxygen therapy all the things that we can bring to bear so the bottom line is the farther along the harder it is and the less complete the improvement but if you catch people early or even in mid-stage you can do a lot just as you've indicated absolutely i've seen that so can you share maybe a story or two of a patient you treated what you found and what kind of things you did and how they improved yeah oh absolutely there and there are hundreds and hundreds like this uh so you know simple example uh of uh of a woman amazing lady uh who's a psychiatrist uh who was having major problems uh and in fact her husband uh said to her that uh you know he said your memory is disastrous she she got to the point where she just couldn't remember anything she's 73 years old and actually she contacted me by email a few years ago and we started going back and forth and she started checking all the various things and she had initially had a lot of the type 2 reduced estradiol progesterone no surprise she was 73 reduced vitamin d poor thyroid all those so all those were addressed she then improved and she actually went from nine so she was in the ninth percentile on her initial cognitive scores she's now at the 97th percentile on her cognitive score so she's just just dramatic she got very as you as you've seen yourself people get into this and she started doing this game called elevate as well as brain hq these are brain training programs and she just got into this stuff and started working it she started dealing with all these brain exercises brain exercises and then interestingly she you know she optimized her various nutrients and then it turned out said wait a minute you know we haven't checked all the pathogens here she ended up having air likia she was from the she was from the new york area and so and she ended up having exposure because of a tick bite when that was treated she continued to improve and she's just done well now she interestingly she had not only improvement in her mri hippocampal volume she also had a pet scan her first pet scan was diagnosed as looks like early alzheimer's her latest pet scan looks like no alzheimer's so she actually improved her pet scan improved her mri improved her cognitive scores and as she said you know she her significant other said to her you know you went from disastrous to just plain lousy and then from just plain lousy to normal and so she now plays she goes out and plays golf with her friends and they can't cheat they can't cheat her anymore she knows how many strokes they've taken incredible and and what did her neurologist say yeah interestingly her neurologist said he said fact she went in she said she said to me she went in there and there were all these people he said it was a very depressing kind of typical neurologist's office everything's bad and she said he came out and he was so excited because he saw how much better she was doing and he started saying to her you know what have you been doing this is incredible and we hear this a lot people will come out and say whatever you're doing keep doing it because something is working here well they they this is really exciting what what is on the horizon in terms of the research you're doing because you know clearly you and i have had experiences we're seeing this over and over our colleagues who are doing this in functional medicine are seeing these results but it's still pretty much dismissed by most traditional neurologists and alzheimer's researchers and even you know all the alzheimer's funding isn't going toward this absolutely what what is on the horizon that gives you hope around the research that we can show the data and begin to change the conversation you know this is a great point because we really do have the opportunity now to reduce the global burden of dementia dramatically you know people wiped out things like polio and smallpox with vaccines global programs we need to have a global program to reduce the burden of dementia around the world by doing these correct things and you know it's this is not magic this is our complex organism that we're dealing with and you have to look at the right things and do the right things to do that where the research is going is to take these same principles what we're finding of course is that the supply is being exceeded by the demand in all of these diseases so we have to increase the supply reduce the demand and there's a there's a unique chemistry for each of these for macular degeneration for frontotemporal dementia for als for lewy body disease and on and on and adjusting this sort of approach to each of these we should be able for the first time to make improvements in all of these different neurodegenerative diseases yeah i think it's true and i'm excited you know we we really are at this forefront of an era when our rethinking of disease is going to provide the key that unlocks so many of our dilemmas in health right from these neurodegenerative diseases to mood disorders to add and autism and of course even all the other chronic diseases and so the approach of functional medicine provides a roadmap to really look at what's going on with any patient so you talk about a cognoscopy it's the same approach to look at whatever's going on right with somebody and what are the dimensions and they're the same in similar things that cause all diseases so it's not like there's 4 000 causes of disease is a short list of things that cause problems and a short list of things the body needs to actually heal and repair and and what you've done is laid that out so beautifully in the end of alzheimer's program it's called the first protocol to enhance cognition and reverse decline at any age and i and i really believe that people get this book and they look at it carefully it's going to provide insights not interest to the brain because you're a neurologist you're focused on the brain but i see this from the context of chronic disease in general to help really understand what's going on and you've really mapped out what are these dimensions it's things like our diet that's full of starch and sugar it's our widespread nutritional deficiencies it's things like heavy metals it's infections like tick infections it's toxins like mole toxins it's microbiome issues in our gut it's our oral health it's all these things that are driving these problems that are causing inflammation and then at the same time like what are all those components that we need to be healthy the right kind of diet ketones and nutrients and hormones and and probiotics and all the things we need to actually add to the body to create health and you do this with with any patient their health is going to improve and you particularly do it with a patient with cognitive issues and any age spectrum and i i wrote an article years ago which which i was very proud of because it was way before anybody was talking about this but i think alzheimer's and autism are often very similar to diseases at different ends of the age spectrum and if you look at the biology of what's going on with these patients amyloid and stuff is different but their brains are both inflamed they often have the same causes of the inflammation and fixing them is often very similar so i think this is really the most exciting era and i and i you know i think you should get the nobel prize for what you're doing i really do i think i think you're way ahead of your time and i think we we really need to think about getting in the research if anybody's listening to this who has alzheimer's who knows someone who's alzheimer's who cares about this issue i think you know we need to fund some big studies to look at this and get this done rigorously and i think it's a really exciting moment where we can begin to do this because we know enough about the brain and we have the big data analytics the artificial intelligence and the science of functional medicine and system biology to really put it all together so dale i can't thank you enough for your work and what you're doing to advance these ideas in medicine and to give people hope where there really was none thanks so much mark and thanks for having me and as you know you and i are both on the same panel with maria shriver and a number of others to change the way we think about this and the problem of course is that there's going to be pushback and so you know over time i think we need to get people to understand that yes there really is something to do especially in the prevention and early reversal area and we really can reduce the global burden of dementia so thanks so much for the great work you're doing thanks so much for having me on i really appreciate it stay safe of course and everybody should check out the end of alzheimer's program the first protocol to enhance cognition reverse decline in any age if you go to apollohealthco.com apollohealthco.com you can learn more about the book learn more about his program learn more about how to actually learn about what you need to learn for your health and your family it's just an incredible resource and i hope everybody takes advantage of it and if you love this podcast please share with your friends and family on social media leave a comment tell us about your story of how you've identified ways to help enhance your brain and uh subscribe wherever you get your podcast and we'll see you next time on the doctor's pharmacy you

Channel: Mark Hyman, MD

Views: 156,676

Keywords: alzheimer's, dale bredesen, mark hyman, the doctor's farmacy, cognitive health, brain health, health podcast, nutrition, health, diet

Id: A_bGCNwqbp0

Length: 66min 6sec (3966 seconds)

Published: Wed Apr 21 2021