 Welcome to the Dr. Gendry Podcast. It's now the sixth leading cause of death for all adults in the United States, and over 90 million Americans are genetically predisposed to get it. Yes, I'm talking about Alzheimer's disease, and unfortunately, most so-called experts will tell you that there's nothing you can do about it. But I've got news. My guest today says that that line of thinking is completely bogus. In fact, he believes that not only can this dreaded disease be prevented, and I certainly agree with him, but it can be reversed. I'm joined again by Dr. Dale Bredesen, New York Times' best-selling author and professor of molecular and medical pharmacology at UCLA. Dr. Bredesen has a new book out called The First Survivors of Alzheimer's, How Patients Recovered Life and Hope in Their Own Words. After a quick break, he's going to give you an exclusive look into his new book, including what most people get wrong about the evaluation, prevention, and treatment of Alzheimer's disease. We'll also share how you can support a healthy brain and mental clarity no matter your age or health. That's right. Dr. Bredesen says there is hope for everyone out there and your journey starts today. So stay tuned. This episode could save a life. We'll be right back. Okay. All right, Dr. Bredesen, Dale, great to have you back. Stephen, so great to see you. I always enjoy talking to you. So last time you were on, the Dr. Gendry Padas was for episode 108, and you shared some amazing news regarding cognitive health, and I still love that episode. But today you're back with even more life-saving information. But first things first, for listeners who might not know, what is Alzheimer's disease? What's going on with their brain? Great point. So dementia by definition is global reduction in cognition. So you begin to lose memory, you begin to lose the ability to analyze things, to plan things, to calculate, to recognize faces, to speak, all these sorts of things. Most commonly, as you know, memory starts to go first. When you look at dementia, the most common cause of dementia by far is Alzheimer's disease. As I've indicated, it is the sixth leading cause of death in the United States, and actually Professor Christine Yaffe from UCSF a couple of years ago published an interesting paper where they just did serial autopsies and showed that if you look at all the cases, it's now actually the third leading cause of death. So however you slice it, it is a very common cause. This is a trillion-dollar global problem. It is costing the US, as you know, Stephen, over $300 billion per year. Big problem. So it really dwarfs. As bad as the COVID-19 pandemic has been, it actually dwarfs the size of that pandemic. So there's a lot of different information out there, and I even heard it again this week with a relatively new patient regarding the causes of Alzheimer's. Some say, oh, it's free radicals in the body. Others say, no, it's the buildup of proteins in and around the brain cells. What say you? Straighten it out for me, please. This is a great point, Stephen, and this is what my laboratory colleagues and I spent 30 years looking at. What is the nature of this illness? Because it's not something simple like COVID-19 where it's a virus, we've got sequence, we know about variants and all that. So as you said, people say it's due to herpes, no, it's type 3 diabetes, no, it's free radicals, no, it's amyloid, no, it's tau, no, it's prions. Just go on and on and on. None, none of those theories has ever led to a successful trial where you can actually improve things. So we just actually posted recently a successful clinical trial. So our view of this is quite different, that this is fundamentally an insufficiency in a network of neuroplasticity. So your brain has, as you know, a whole set of things just as you describe with cardiovascular disease. There's a set of things. You need that blood flow, you need the oxygenation, you need the patent arteries, you need all of these things to get yourself the best working heart. Well, same thing as you pointed out, same thing true for your brain. You need the mitochondrial function, you need the support. And what happens is you've got a supply and you've got a demand. And for people with cognitive decline, the supply is being exceeded by the demand chronically. And it can be for four different reasons. It's because either you don't have enough energetic support, and that's mitochondrial function, oxygenation, blood flow, ketones, glucose, that, or it can be because you don't have enough trophic support. And that is estradiol, testosterone, you know, and all that sort of nerve growth factor, all the things that are supportive. Or it can be because the demand is too high because of inflammation, all sorts of pathogens, or because there is toxicity. You've gotten exposed to biotoxins or inorganic toxins or organic toxins. So those four groups, if you put you on the wrong side of the supply and demand, then no big surprise, your brain starts to involute. I think one of the things I love about you is that you've really broken down in your previous books and now particularly in this book, there are different types of Alzheimer's just like you've alluded to. And the idea that this is a one size fits all, which is still what's out there in the world, there are different things you should do for all of these different factors. Right. Absolutely. So this one, you know, let me, let me, let's stay on this topic. What are some of the indicators that I should be looking for, family should be looking for a pre Alzheimer's or Alzheimer's? I mean, can you spot it a mile away? Are there tests now to help us, you know, look at who's at risk? Let's start there. Yeah. Stephen, I know I'm so glad you brought that up because this has been one of the biggest reasons that this is such a common disease and has been so untreatable. We hear all the time the term mild cognitive impairment. And that's unfortunately a damaging term. That is the third of four stages. So there are four stages that you go through, pre symptomatic, at which point you're only seeing it with a PET scan or spinal fluid. And that can last several years. Then SCI, subjective cognitive impairment, where you know things aren't what they were. And you're still scoring in the normal range on your testing, but you can notice that there are slip ups. And there are often things like having trouble navigating, that's a common one, having trouble remembering a phone number where before you remembered phone numbers or before you remembered numbers, having trouble calculating a tip, having trouble recognizing faces. Those are all early signs. That's when you want to get this. If you don't get on prevention, please get in as early as possible. SCI lasts on average 10 years. So what that means is we have a tremendous window of opportunity to make it so that nobody goes on to get full on Alzheimer's. Virtually everybody with SCI responds beautifully to appropriate evaluation and treatment. Now if you don't do anything during those 10 years, you go on to typically go on to MCI, mild cognitive impairment. And this is like telling someone, don't worry, you only have mildly metastatic cancer. It is a late stage of this thing that ends up as Alzheimer's. So it's like saying we're not going to diagnose diabetes until you have ketoacidosis, it just makes no sense. So MCI is mild cognitive impairment and we still get good results, 84% of the people in our trial who had MCI or early Alzheimer's improved their scores, but it's clearly easier with SCI than it is with MCI. And with MCI, each year of MCI, 5 to 10% of the people convert to full on Alzheimer's. And by definition, that's the fourth stage, by definition that means you've begun to lose the activities of daily living. So this is why the idea of let's see what Alzheimer's isn't treated is such a problem. We should be looking much, much earlier than that. And again, it says if in your practice as a cardiac surgeon, you only looked at people after they'd had a large MI, it just doesn't make sense. You want to get into people earlier and earlier. So that's been the big problem. And those are the sorts of things to look for. And then as you said, yeah, then you want to go get appropriate labs. You want to look at your inflammatory status. You want to look at your glyco toxicity status. What's your HOMA IR? Do you have other toxins? Do you have vascular disease? These are all critical. So many times I've noticed that it's the spouse in one way or another that first recognizes this. And often the other spouse is maybe unaware or certainly doesn't want to address it. My problem is that these people may go to their well-meaning physician. They may even see a neurologist. But the neurologist says, oh gosh, this is just, you're getting old and of course you're going to forget these things. How do you see that we should be intervening at this early stage? What can people listening to this podcast do either by themselves, by your book, obviously? But how do they get through this, oh, there's nothing you can do about it, that's normal. This is a great point. And so you should have a cognoscopy. We all know that when we turn 50, what do we do? We get a colonoscopy. So helpful to make sure we're not going to get colorectal cancer or that we catch it early. Same thing for a cognoscopy. For anyone who's 45 years of age or older, please get a cognoscopy. And that's three simple things. It's a series of blood tests that are looking at these various parameters. So just as we all know what our blood pressure and our cholesterol are, we should also know what our risk factors for cognitive decline are. We should know things like, do we have insulin resistance? What is our HOMA IR? We should know what is our HSCRP? Do we, in fact, have any evidence of systemic inflammation? One of the important things, oral microbiome, you probably saw just this past week that the company Cortzyme reported that there now they've developed a treatment that's supposed to be for Alzheimer's, which actually addresses one bacterium in your mouth, which is P. gingivalis, which has been found in the brains of patients with Alzheimer's. This inhibits a protease. Now, unfortunately, the trial failed, but they're on the right track with the fact that this is one of the contributors. And so absolutely, your oral microbiome important. So for a cognoscopy, it's some blood tests. It's a simple online cognitive assessment. And then only if you've got symptoms or you're scoring poorly on the cognitive assessment, please also include an MRI with volumetrics. That's optional if you're just there for prevention and your scores are good. But if everybody would simply do that cognoscopy, we could really lower the global burden of dementia. Last week, I had a patient who had some memory issues and got an MRI from a neurologist. The neurologist said, oh, you got nothing to worry about. This is normal brain shrinkage with age. What say you? Yes, that's a great point. So if you look at MRIs across the period, then on average, you lose about, if you're a quote normal person, you lose about 1% of the gray matter volume per year. And you lose about 3% to 3.5% if you have Alzheimer's or pre-altimers, MCI. In the trial that we just did, we took people with MCI or with early Alzheimer's. And interestingly, their gray matter actually grew. It actually got larger, even though they had the conditions that's associated with more shrinkage. So this has been the problem because we as physicians have not in the past had anything to offer these people. We've developed this whole way of speaking. It's not that bad yet. It's normal aging. You're getting a little older. Don't worry about it. This is because we've had nothing to offer. We've got to change that approach just as you've been doing for years now. We've got to get in there early. We've got to say to people, yes, there's a tremendous amount you can do about it. And let's make sure that you do that so that you don't go on to get full-on Alzheimer's disease. Well, again, I think this idea of just telling people, yeah, it's normal brain shrinkage. This is an old-fashioned approach. So what do you think are the biggest threats out there? And we have become friends, and I greatly respect your work. So I want to put you on the spot. What are the biggest threats to brain health that you see out there that we can do something about if we recognize them? Yeah, this is a great point. And you and I have discussed there are dozens of things that contribute. But you're right. There are a few things that are really a problem. And part of it is just the attitude of the physicians, just saying that, hey, don't worry about it because there's nothing to be done at this point. But one of the common things that people, a couple of the things that are critical that people don't recognize, one of them is dropping your oxygen saturation as you sleep. And it's easy to check. You can get an oximeter. You can get itself an Apple Watch. However you want to do it, get a sleep study if you want. But it's important to know. And in fact, there was a beautiful study a few years ago where they simply looked at the average oxygen saturation during sleeping versus the size of various nuclei within your brain, including, by the way, the hippocampus. And in fact, there was a direct correlation. If you're running around, if you're sleeping every night and you're averaging down at 91% or 90% or 89% or 88% for your oxygen saturation, you have a smaller brain on average. If you're up where you should be in the 96% to 98%, you're going to have, on average, a larger, healthier brain. So that's a big one. The second thing is the oral microbiome. We're realizing more and more. I mentioned the P. gingivalis. But there are others, T. dentocola, F. nucleotide, and a number of these, as you know. Getting the appropriate gut microbiome is so important. And getting the appropriate oral and sinus microbiome turns out to be important as well. The big surprise has been, you find those same organisms inside the brains of patients with Alzheimer's. And guess what the amyloid is? It's there to fight those organisms. And again, same sorts of things that's been found in the plaques of the arteries. You've got these bacteria, as you call them, gut buddies and things like that. These bacteria are finding their way to your blood vessels, to your brain. They're actually involved sometimes with tumor formation. So it's amazing how these things get around your body. And your holo-biome is so critical. And then the third thing I would say is people don't realize, unfortunately, the toxins they're exposed to. Please, everybody, get evaluated. Make sure that you don't have a house full of mold-related toxins. Again and again and again, these things come up. And I have to say, I was never trained to look for those. We didn't think, in my neurology residency or fellowship, that mold toxins had anything to do with cognitive decline. So I learned the hard way, seeing people, several people, who turned out that that was their biggest problem. And until you address those, you're not gonna get people to be much better. So for optimal outcomes, make sure to include that. And then, of course, the fourth one is what you preach about a lot, things related to your diet. And so many people about something like 80 million Americans are insulin resistant. It may be more than that. And this is such a common problem with cardiovascular disease and with dementia. Yeah, it's shocking how metabolically inflexible the vast majority of Americans are. And for those of you who don't know what that means, it simply means your mitochondria, your energy-producing organelles, should be able to shift on a dime between using glucose as a fuel to make energy or using free fatty acids or ketones to make energy. And in my upcoming book, Unlocking the Keto Code, it turns out that if you're overweight, overweight people, 98% of overweight people are metabolically inflexible. And 99.9% of obese people are metabolically inflexible. So it's actually worse than any of us, including me, even realize. And to your point, it's no wonder that this is happening to us. Okay, so let's suppose, before we move on, let's suppose you're diagnosed with Alzheimer's. Someone tells you or your loved one, that's what you got. What now, in your opinion, should be the standard of care? Yeah, that's a great point. And so that's what we have, now that we've published the one trial, we're now putting together a larger randomized controlled trial that will start early next year. And in that one, we have one arm that is doing the optimal care, as our hypothesis of the optimal care, which has worked for many people. And then we've got another group, which is standard of care. And so standard of care, as you know, has not worked well. You don't see people turn around, you don't see people get better. And so the optimal care is to address those things. So you have to kind of flip the script, because we've had nothing to offer as physicians over the years. Everything, just as it has been, as you've pointed out in your books for cardiovascular disease, everything is backward. Starting with the doctor saying delay, it's not that bad yet, come back later, this is normal aging, to then saying, okay, get on a drug, and then wait all these things. And then the other thing is, they say, we're gonna treat everybody the same. We'll give them everybody the same drug. So what we wanna do is flip that around and say, for each person, we're going to discover what are the contributors to your cognitive decline? In some people, it is more about their metabolism. In some people, it's more about exposure to mycotoxins. In some people, it's more about exposure to air pollution. That's been a common one that people look at. In some, as we talked about, it's related to their oral microbiome. Herpes is another association. So what that you really wanna do is for each person identify the various contributors and then address each of those contributors. And even addressing a few of them, people will begin to feel better and begin to score better on their testing, begin to do better overall. And as you address one after the other, they typically do better and better. And we've had the longest people now have been on for nine and a half years and are still doing well, started in 2012. So there is a tremendous amount that could be done starting with a serious evaluation and then getting these. And there are some core things for sure, getting people, as you indicated, insulin sensitive, so important, getting them into mild ketosis. As you indicated, it's that metabolic flexibility. Normally, you can go back and forth when things are good between ketones and glucose. With people with cognitive decline, they've lost both of those. They've lost the glucose because of their insulin resistance. They've lost the ketosis because the insulin, having a high insulin prevents you from getting into ketosis, among other things. So they have the worst of both worlds. So let's talk about the recode protocol. And it's not a magic pill or a quick fix. So when people say, I want the Bredesen recode protocol, what pill do I take? That's not what you're talking about. And as you and I both know, it takes serious dedication. And for most people, it means making some major lifestyle changes. So tell our listeners and viewers, what is this protocol? Why is it called recode, anyhow? Right, so recode is for reversal of cognitive decline. So when we first saw people reverse their cognitive decline, actually one of my coworkers suggested, well, why don't you call it recode for reversal of cognitive decline? Well, okay, well, that's a good name for it. So the idea then is you look at what's driving it. You're going to improve these things. And yes, it's helpful to work with a health coach because what you were really doing is we are changing your fundamental neurochemistry. This came straight out of our 30 years in the lab, looking with transgenic mice, what we called mount timers, looking at fruit flies, what we called alts flyers, looking at cell models, all this stuff. And then translating that to what can you do with a human being? And so, yes, it begins with the basics. Diet, a ketogenic diet, mildly ketogenic plant rich diet, which is high in things like choline and getting you the appropriate neurotransmitter precursors that you need and things like that, high in fiber, having appropriate time for fasting. We call this keto flex 12-3 because it gets you into mild ketosis and because it is flexitarian and you've got the time of 12-3 for fasting. And then exercise. And interestingly, there's more and more that we understand about exercise and how it can be helpful. People using things like katsu bands and exercise with oxygen therapy that to enhance what you're actually getting from the exercise and you're getting insulin sensitivity and you're getting better blood flow, you're getting better oxygenation. And then sleep, one of the huge issues that's not looked at carefully enough in many people. And then stress reduction. You wanna shrink someone's brain, put them under stress for a while, their brain will shrink. So we wanna optimize that as well. And then basics, brain training, detoxification and targeted supplements, all part of the protocol. And I do believe these various drugs will be much more successful when they are used on the backbone of an optimal personalized protocol. So this is nothing more than we're addressing and optimizing the neurochemistry because it's the neurochemistry that's been out of whack to give you this cognitive decline to begin with. Not surprisingly, you and I have very similar views on how food choices as well as time restricted eating play a huge role in both the prevention and the reversal of Alzheimer's. Would you give our listeners just a little snapshot of what the timed eating is in your plan? I know we do this together. So tell people what you're talking about. Yeah, great point. So what we recommend is that you wanna have a period that helps you in a number of ways to get you into some autophagy. So you wanna have a period of fasting. Fasting turns out to be very important for many things, including your immune system, including your lipid status, including your ability to clear toxic lipids and proteins and damaged mitochondria and things like that from your brain. So you wanna have a minimum of 12 hours. We usually recommend if someone is ApoE4 negative, and that's three quarters of the population, 12 to 14 hours. If you're ApoE4 positive, and that's about a quarter of the population, you wanna have 14 to 16 hours. And some people go longer. So for example, my wife and I like to do typically eight to 10 hours of eating and then the rest of the day. So we're ending up with a 16, 14 to 16 hour fast before you're eating again. And so that gives you time for a couple of meals and you can have appropriate fasting while you're sleeping. It's very helpful and we're doing for everybody in this upcoming trial. Everybody will have continuous glucose monitoring, CGM. So that gives you a couple of weeks and people are so surprised, as you know, Stephen, you see people spike their glucose and equally as bad, you see people have it drop into a trough. So they go to bed at night because they've had a higher carb diet and suddenly their glucose is 45 and they're waking up in the middle of the night feeling horrible. And so you want to avoid both of those. You want to avoid the spikes, you want to avoid the valleys and get a much smoother glucose curve. So what we want to do is that 12 to 16 hour fast and then three hours before you go to bed at night because you certainly don't want to go to bed with a high insulin. Yeah, I think that's so critically important. And I've been trying my best to get folks to please stop eating three hours or even more before you go to bed. It makes a huge difference in outcome. Your protocol also includes taking a variety of supplements, bless your heart. Can you share a couple of the most important ones with listeners? Yeah, and again, this is all coming from mechanistics. And so let's just talk for 30 seconds about the immune system. This is critical. As you know, if you look at, this has been very instructive with COVID-19. What happens with COVID-19? Your innate system is on fire. You've got those cytokines pouring out. Your adaptive system has not cleared the virus. And so you die from cytokine storm. In Alzheimer's, very much the same thing. Your innate system is ongoing for years and your adaptive system hasn't cleared the various things that you've been exposed to. So you don't die of cytokine storm but you die of cytokine drizzle. And guess what? Part of the innate immune system is amyloid beta. So it actually makes perfect sense. Your body is responding to these various insults. So therefore, we want to improve your adaptive system. We want to reduce your inflammation. Now, sometimes that means using things like low dose naltrexone. Other times it simply means supporting things with zinc, vitamin D, kind of the standard sorts of immune support that we think about when we look at COVID-19 and STL-Cysteine, things like that. So yes, there are many different supplements that can be used. And what's amazing to me is we've always been told that the arsenal for Alzheimer's is zero. There's nothing you can do to prevent it, reverse it, or slow it. And in fact, the opposite is true. It's a huge arsenal and the positions who are excellent can pick out here the most important ones for each person. Here are the high priorities, here are the low priorities. Now some of the ones I happen to love, I like whole coffee fruit extract because it increases brain-derived neurotrophic factor. Again, some people this is gonna be more helpful than others. You can actually measure your BDNF in your blood if you like. Magnesium three and eight is another good one. I happen to like Resolvans. With Magnesium three and eight, of course, Rosong Liu from MIT did some very nice work showing that that's helpful for many people with their cognitive benefit. I like Resolvans. Professor Charles Searhan at Harvard has done some nice work on Resolvans. The issue there with inflammation, again, it's more complicated than we often hear. Number one, you want to resolve it. It's not just about an anti-inflammatory. You want to resolve what's there. You want to prevent the further. And most important of all, you want to remove the source. And if that is poor dentition, okay, so be it. Remove that source. You can use all sorts of things like dental siden. You can use things like Revitin toothpaste that are probiotic toothpaste now. So you can restore a good oral microbiome. One of the things that the people in the new trial are also getting is these cone beam analyses because so many people will turn out to have unknown deep abscesses that haven't been picked up. And there is another source of infection, another source of inflammation, another inducer of cognitive decline. So getting that optimal is critical. And then of course, the classics, I do think things like S-acetyl glutathione. So many people are not doing so well with their detox and having appropriate glutathione. Probiotics and prebiotics, as you've talked about, of course, your gut buddies, as you've said, these are so important. And I certainly am religious about taking prebiotics myself. I think these are critical. And by the way, without going into any gory detail, I'll just say that I followed some of your suggestions and the various, the exact things that you described in your book happened, my gut has done much, much better since I've done the right things. Whereas when I was in medical school, things were not as good. And so just to say thank you, Dr. Gundry. I think we're all on the same page with probiotics and prebiotics. And then making sure that there's plenty of fiber. I think fiber is undersold because we think of fiber as being, like your grandfather's Oldsmobile, so what, big deal. But very, very important for your lipids, for your glycemic load, for your detox. I mean, it's just amazing how important, of course, for gut healing. So all of those I think are helpful ones. And of course, omega-3s and acetyl-cysteine. These are all things that can be quite helpful. You know, it's interesting, there's this current little baby aspirin controversy. And one of the things that a lot of people don't know is that long chain omega-3 fats are converted into resolvents by low-dose salicylic acid, which happens to be aspirin. So for the last 20-odd years, I've been asking my patients to take a baby aspirin several times a week not to prevent heart disease, but to activate their omega-3s into resolvents. And in fact, there was a very famous paper a few years ago saying omega-3s don't help with inflammation. But when you read between lines, they gave them nothing to activate their omega-3s into resolvents. So I had a good chuckle when I saw that. Very interesting, yeah. I think, you know, the human organism is complicated. And medicine has changed fundamentally since we were training in the 20th century from a discipline in which doctors couldn't begin to look at all the different pieces of how the human organism worked. And so therefore they would focus on this prescription because that's what we could do for the last few thousands of years. But now it's a new era. 21st century medicine is fundamentally different. And now we're beginning to be able to say, here's how this very, very complex machine works. Now there's a lot we don't know, granted, but there are so many of these points, just like the one you just made, where we're beginning to understand what it actually takes to make the biochemistry work functionally. And this is exactly what we're doing with the neurochemistry. And I believe that this can now be adapted to all of the different major degenerative diseases, Lewy body disease, frontotemporal dementia, ALS, all of these things. And we're actually starting with the project. We've got the first patients with macular degeneration, where again, you evaluate the things that are actually driving the macular degeneration. And then you go after those. And we'll see, we'll see how it goes. But this is the way that we should be able to approach all of these complex chronic illnesses. Well, that brings me to the next point. Does this program work for everyone? And if it doesn't, why not? Yeah, this is such a good point. So thank you for asking it. So there are several barriers. Of course, it doesn't work for 100% of people. In our trial, 84% of the people improved. So the ones that didn't, you could see why they were not improving. As an example, one person, we could see that this person had very high levels of mycotoxins in their home. Then the person said, I don't wanna remediate it. I don't wanna leave the home. I'm gonna stay right here. So okay, continued exposure, continued decline, continued problems. Although to be fair, even just fixing the metabolism is a good start. So that's the first thing. So it depends on when you start the program. If we can get everybody to start when they either as prevention or SCI, you could pretty much eradicate this disease. We unfortunately are dealing with everybody at the other end, MCI and Alzheimer's disease. So how late you start is one of the critical determinants to how easy it is to get better. The second one is how compliant. For people that are really getting themselves into ketosis, doing all the right things, they almost always get better. And that's exactly what the trial showed. 84% of people, we had an optimal situation with health coaches, et cetera. One of the big questions from the trial is, can we now make it much more practical, much easier for people? Well, okay, that's the way we're headed, but you had to start somewhere. First is, can we turn it around? And the answer is in most people, yes, especially if you don't wait too long. Then the third issue is, for people who have severe toxic exposure and have lost a tremendous number of synapses, no question, it is tougher. And so for the ones that where we detect high levels of toxins, you really do have to stick with it. As you know, the detox physicians, like Dr. Joe Pizorno, for example, they talk about the fact it takes years to get rid of these. Dr. Neil Nathan as well, they talk about the fact that it does take years to get rid of some of these toxins. So I'm always happy when I see someone who's mostly got issues with insulin resistance and inflammation, metabolic syndrome, we can fix those people fairly quickly and fairly completely. It's the tougher ones that have the severe toxicity. So those are three big parameters that determine it. And then the other thing is that people give up early because they don't yet understand, they don't realize that yes, this is something you gotta stick with and their doctors will tell them, well, you know, just take a pill. So we have to get people to come in early and to stick with it because this, remember this is a disease where you don't get a diagnosis typically for about 20 years after the pathophysiology starts. So kind of circling all the way back, what type of tests would you advise listeners to ask their doctor in order to learn more about their risk and what do you do if your doctor laughs you off when you request these tests? Which quite frankly happens a ton in the people who end up seeing me. You know, that's so important, Steven. You know, I usually tell people when the doctor laughs them off, I say, if you've got something better, please let me know. Here are some published papers and a couple of books that show results. If you've got something better, I'd love to hear about it. If not, then please suppress the laughter because there are some stuff going on out there that's getting better results than you are. So, you know, it's great. We'd all like our doctors to be up on the latest. One doctor said, doctors are too busy to read. That horrified me. So we hope doctors aren't too busy to read. But the other thing is what we want people to know are those very things, and they are very much relevant to the things you've talked about with cardiovascular disease. We'd like them to know what is their ongoing inflammatory status. So at least in HSCRP, you may also want to look into a couple other things like your albumin to globulin ratio, maybe your TNF, maybe your IL-1, some basics like that. But really, you just mainly need HSCRP. And Stephen, I don't know if you like to use other things, sed rates or other cytokines that you look at or not. Yeah, I don't look at sed rates very much. I think they're just too inaccurate for a long-term look at things. And the same way I feel about fibrinogen. I do like IL-16 recently. I've got a paper coming up at the American Heart Association in a couple of weeks looking at that as a risk factor for cardiovascular disease. And we can now measure that. So that's another thing I look at. But you're right. People really, I have third-year family practice residents rotate through my clinic. And I can tell you that not one of them has ever been taught about a fasting insulin level. Seriously. Yeah, it's amazing. They go, what's that? And none of them have ever seen a HOMA IR or know what it is. This is, IR stands for insulin resistance. And yeah, and you and I think about this every day and we go, well, of course, that's standard of care. These are about to go into practice in family medicine. I mean, very talented individuals, but they've not been exposed to the basics. Yes, it's true. And it is because there is a fundamental schism in medicine right now. There is 20th century medicine, which is about what is it? Make the diagnosis, write the prescription or do the surgery. And there is 21st century medicine, which is about why is it? What are all the things? This is systems medicine. This is functional medicine. This is precision medicine going after the things that are actually changing the pathophysiology. And as you indicated, you wanna know your HOMA IR, your fasting insulin, your hemoglobin A1C, your fasting glucose, all of those things because they together give you a picture of what's going on. You have continuous glucose monitoring, very helpful for people. You see what spikes and what are the valleys and all those sorts of things. And then we wanna know your hormones and growth factors and nutrients, things like vitamin D and things like your progesterone, pregnenolone, estradiol, testosterone, all these sorts of things because they are all playing on your synapses to tell you whether you are in this synaptoblastic state, the ability to make and keep synapses, or you're in a synaptoclastic state where you're pulling back. Literally, your brain is simply saying, I'm gonna have to protect myself. It's going into a downsizing protective mode and in so doing, it is impacting the very mitochondria you were talking about a few minutes ago. And so those are the sorts of things you want. You also wanna know if there's vascular damage, your specialty, so things like your triglyceride to HDL ratio and your LDL particle number. And as you often talk about your SDLDL, all these things critical for understanding whether you are having a high risk or a lower risk. All right, I wanna jump to your new book, The First Survivors of Alzheimer's. Now it features stories of seven unique patients who committed to the RECOAD protocol. Can you tell us a few of those stories and why you decided to feature them in the book? Because they're really moving stories, they're fantastic. They are, and I have to say when we were, when we've talked to some of these people, I mean, they became tearful. It's their amazing story. So back in 2012, the very first patient, I called patient zero in there, called me up after three months and said, oh my gosh, my memory is so much better. I'm doing so much better. And I thought, wow, yeah, this is amazing. The research that we had done over the years, at that point only about 20, a little over 20 years, now over 30 years, where we were looking at these things. We said, okay, this is driving us in the right direction. Following the APP signaling, following what actually is driving your synapses to continue or to pull back is helping to drive us in the right direction. So as we began to hear, being one person after the other started to do this, the stories are such beautiful stories. And I thought that they could do a couple of things. Number one, they can inspire people not to give up, to say, hey, look, I did it. It really changed my family. The other thing I thought was, they can give them their protocols. They can say, look, this is what I did. This is what I tweaked. This is how I optimized it for myself. And the third thing is, there are wonderful stories about how they impacted the families. Because the first couple of books were a lot about the science and then the clinical translation. But this is the human nature part of it. This is people saying, great example, you know Julie very well. And she talks about, of course she has a 4-4 and highest risk. And she talked about when she first was diagnosed and talking to her son, who started crying and said, mom, I don't want to lose you. And then about how she got better and then ended up going to her son's wedding. So it's just a beautiful story. And my hope is, this is the beginning, as I said in the second part of the book, toward a world of survivors. We really need to make it so that we reduce the global burden of dementia. And imagine that we could stop half the people in the world. There are over 30 million people in the world right now with Alzheimer's. Over 6 million in the US alone. About 45 million of the currently living Americans will die from Alzheimer's. Which is a horrible, horrible problem, as you know. Horrible way to go. And so giving people the inspiration and the know-how to make a big difference was just wonderful. It was really a labor of love just going through these stories. And then the last half of the book is about, okay, what are the updates for the protocol? What have we learned in our nine years since we had the first patient back in 2012? Yeah, they really are great stories. How long, just in general, does it take people to see a difference? Or is there a general rule? No, that's a really good point. And you have to remember, they've been doing this. It's typically the pathophysiology has been there for years. SCI alone averages about 10 years. So typically when we see them, it's been years. And it typically takes, I always tell people, give it three to six months. Now that's three to six months after you do the right things. So if you don't do the right things, it's not gonna happen in three to six months. But get yourself into ketosis. Make sure that your sleep is okay. Make sure that your oxygenation is optimal. Make sure that your gut is healed. Make sure that your lipids are looking good. Make sure that you are insulin sensitive and you've now metabolically flexible. Once you've done those things, give it three to six months and most people will do well. Now we've had one person as early as four days because this person had massive mycotoxin exposure. Just getting out of there four days later, she was already starting to improve. But that's the exception. Most people, you've gotta fix a number of things. And so we usually tell three to six months. But some people are still doing better and what'll happen is they'll plateau and then we find that, oh, there's something else that's been missed. Now they go to a higher plateau and then maybe they'll add one more thing. There's another pathogen or they'll add low dose naltrexone and improve their immune system. And then they'll get a higher plateau. So we wanna keep people getting higher and higher plateaus. And of course that means for a quote, normal cognition, people tend to get better than their normal cognition. As you well know, by doing the right things. Now this is not a one and done. Once you get these results, you don't go, okay, I'm fine, I can go back to doing exactly what I did before. No. That's, yeah, exactly right. I'm so glad you brought that up because you wanna keep optimizing and you wanna stick with it. Now to be fair, there are people who will have, once a week, go out of ketosis and they'll cycle in and out, which is not such a bad thing, cycling out once a week, especially for the people who have low BMIs and really need that caloric. You gotta be careful because some of the people at the low end of the BMIs can hurt themselves by jumping into too much fasting at the beginning. You gotta, again, you have to remember, this is a disease of insufficiency. Interestingly, even though it's born of excess, typically excess sugar and things like that, so you gotta kinda walk that midline where you're not taking things away too much. But yeah, absolutely fine to get off occasionally, but as you indicated, you wanna continue this for your life because it will continue to signal to your brain, yes, I want to be able to make and keep synapses. It'll keep your memory sharper. It'll keep your cognitive abilities better overall for many years to come. So our goal is to get everyone to be sharp to a hundred. Now, sounds good. I just, one of my 97-year-old patients from LA drove out to see me this week, as sharp as a tack. And he's a three, four, and he still runs his business, and I've been taking care of him now for 15 years because his family brought him to me and said, you know, he's so important, we gotta keep him around. He's 97 and he's thriving, so you're right. I think people need to understand, not only there is hope, thanks to you, but that this is, you know, if you have these signs, you know, jump in, dive in, it's worth it. And the payoff is, you know, a great brain and life for a very long time. Absolutely. And I think it's something we're not used to. People keep saying, oh, you're 45 now. You can't expect to be as sharp as you were. Oh my gosh. As you said, people should be as sharp as a tack until they're a hundred. So, you know, this guy's 97, he's doing very, very well. And you know, this is the new era of medicine. This is, you know, this is functional medicine and we can all stay well and stay functional well into our late 90s or beyond. Yeah. I know, I'm interested in time. I know you gotta go. What's next for you in the Recode Protocol? You've kind of filled us in on where you're going, but anything on the horizon new and exciting? Absolutely. Yeah, thanks for asking. So three things. So number one, we're doing this larger trial now. We had very exciting results. And I should have mentioned, you know, that both the gray matter and the hippocampal volume in this trial did better than normals. So very exciting to see that. So we've got a larger trial now that will be a randomized controlled trial starting early in the year. Second thing is that we are adapting this for other neurodegenerative diseases starting with macular degeneration. And we've had good results already with Lewy body, but you know, what about ALS? What about frontal temporal dementia and things like that? And then the third thing is called the CERA trial. And that's not started yet, but that's down the line. Severe Alzheimer's reversal attempt, CERA. And the idea is what about the people, because we looked at people with mochas of 19 to 30. Now that's MCI and early Alzheimer's. What about the people with mocha scores of zero, late end stage Alzheimer's? We've had some anecdotes where we've gotten some improvements. We've never seen them go from zero to 30, but we've seen them go from not dressing to dressing, from not talking to talking, tremendous subjective improvements. So we need to ask, what do we need to include to get people who are very severely involved to bring them as close back to normal as we can? Does that take stem cell addition? Does it take intranasal peptides? Does it take hospitalization? What does it actually take to do that? So that's the third piece of this going forward. And those are the directions we're going. All right. Well, I know you gotta go to a conference and lecture, and I really appreciate you tearing yourself away. Because this is, as you know, this is really important and exciting information that this is not the end of the world as everybody expects when they're given this diagnosis. So much that can be done. And again, please encourage everyone. When people are really late, I tell them please bring in all the children. Let's make sure that you end this problem with this generation. And that's something that we can all do. So great to talk to you, Stephen. I really appreciate it. Always love talking to you. You're always doing exciting stuff. And I look forward to your upcoming book. As you know, my wife and I are huge fans of all of your books. So thank you. Well, it's a mutual admiration society, I assure you. So, and thanks for all your great work. And I know we'll be talking off camera soon. Thank you very much. Please stay safe. Watch out for those mudslides and stay away from COVID-19, okay? I plan to. All right, take care. Thanks Stephen, thank you. Bye-bye. All right, it's time for the audience question. This question comes from Oksana Hernandez on YouTube who says, dear Dr. Gundry, you are simply amazing and very inspiring. Well, thank you. Love your work. I've done my diet transformation now. Struggling to find a lectin-free substitute for wheat flour to use for bread and pancake making. We can't achieve the same consistency and viscosity with coconut flour and almond meal. I'll try millet and sorghum flour, please advise. Well, the good news is that I just so happened at Gundry MD to have a really fabulous bread mix and also pancake mix and chocolate pancake and waffle mixes that we at the Gundry household have fooled so many of our guests into thinking that they are actually having pancakes and waffles and they are shocked when I actually show them the box and the next thing I know they're ordering it. There's all sorts of ways around just coconut and almond flour and don't get me wrong, they're very useful, but a lot of times we've found that psyllium fiber is one of the real tricks. Tapioca fiber is one of the real tricks, cassava. And play with it. There's lots of great recipes online. We have recipes in our books on how to do this. So don't despair. You can actually get the mouth feel that you're looking for either from our mixes or by going online and looking at that. And again, thank you so much for writing me about how well you're doing and my work. I really appreciate it. Time for the review of the week. This week's review comes from Cheryl H on YouTube who watched my interview with Catherine Arnston. She said, thank you. Thank you for this interview, Dr. Gundry. I learned so much that I didn't know about spirulina and chlorella despite hearing people praise them for at least 40 years. And now I know about a brand that I feel I can trust as well, which has been the main thing holding me back all these years. Now I can't wait to introduce these superfoods to not only my diet, but my daughters and granddaughters as well. So once again, you have profoundly improved the direction of my health just as you did when you introduced me to the concept and effect of lectins, which I've since found to be the primary cause of most of the arthritis I have suffered with for the past 10 years. You and Dr. Jason Fung have been godsends in my life and I could not appreciate you more. Thank you, thank you, thank you again and again. Well, thank you, Cheryl, for sharing. Just almost every day, I hear people with arthritis shocked that when they get these trouble making foods, electing contained foods out of their life, their arthritis resolves and often resolves quickly and dramatically. So thank you for writing in, I appreciate it. Spirulina and Chlorella are really great algae's and aquatic organisms to get into your life and I'm glad you like that show, it was fun. I'm doing this for you guys and keep writing in because we'll read about it and we'll see you next week because I'm Dr. Gundry and I'm always looking out for you. Before you go, I just wanted to remind you that you can find the show on iTunes, Google Play, Stitcher or wherever you get your podcasts because I'm Dr. Gundry and I'm always looking out for you. Thank you.