#043 Dr. Dale Bredesen on Preventing and Reversing Alzheimer's Disease

Protein Aggregation: Protocol

He's got a really interesting multi-pronged protocol for preventing and also helping treat mild cognitive dementia and Alzheimer's disease. Thanks very much, Rhonda.

"So maybe we can start a little bit by just talking about some of the characteristics and pathological distinguishing features of Alzheimer's disease and Thank you."

Alzheimer Prevention: Prevention

Hey friend, welcome back. Today's episode features Dr.

"With Alzheimer's, there are dozens of things that can be contributing. And so what we want to do is address all of those. Yes, if you have pathogens, many people have, for example, Borrelia from Lyme disease or a Lyme co-infection like Bartonella or Babesia or Ehrlichia, things like that, then those need to be addressed. And of course, you need to change the underlying biochemistry. So as you indicated, there are specific biomarkers. So we want to know your HSCRP. It's a marker of inflammation, of course. We want to know your homocysteine, the marker of methylation. If you're not methylating appropriately and your homocysteine is high, then you are at increased risk for neurodegeneration. And of course, it's been published that you have a more rapid decline in your cerebral gray matter volume and hippocampal volume if you have a high homocysteine. Is that because of vascular reasons? What's the homocysteine? The publication did not distinguish. It just simply followed people over years and looked at the rapidity of the decline in volume and could show that not only was it more... Literally, you could put the rapidity of it on a graph with homocysteine and it fit very nicely. But then if you improved the homocysteine and brought it back to normal, they were looking at less than 7 as being normal, not less than 13, which is often used in labs. Less than 7. 7 as being normal. Then, in fact, what happened was people actually stopped their decline and leveled off. So it's suggested that this is a causal relationship, that it is a mediator of cognitive, well, of change in cerebral volume as well as cognitive type. Independent of other biomarkers? Independent of other biomarkers, yes. Wow. So we want to know that. We want to know whether you have glycotoxicity. So we want to know what is your fasting insulin. And again, people will accept it way off the scale. We have an unfortunate situation where classically we have accepted laboratory values as within normal limits, W and L, very arbitrarily as being within two standard deviations of the mean. That actually makes no sense physiologically. It just says that there's a distribution there. It doesn't say that that's optimal for your health. So we'd like to know what your fasting insulin is, and optimally it would be less than five or less than five. Although, again, within normal it goes much higher than that. We'd like to know your hemoglobin A1c, which again is a marker of your, essentially over the last two months, your serum glucose. We'd like to know your fasting glucose. These three actually give you quite complementary pieces of information, all related to this type 1.5 that I mentioned, the glycotoxic type. And then the atrophic, as you can imagine, there are lots of things. We want to know your vitamin D. And again, we want to see that it's optimal, not suboptimal, but within normal limits. We want to know your pregnenolone, progesterone, estradiol, testosterone, free T3. Now, we'd like to know your brain-derived neurotrophic factor and your NGF. There's no simple way on a clinical lab test today to get those. So you have to infer them from other things. What is your hippocampal volume? What have you been doing? If you change these various things we've been talking about, you're likely to have a decrease. Have you been exercising? If you're not exercising, your BDNF is likely to be lower. So we want to look at all of the trophic support for your brain because these are critical things. If you're going to make and keep a large network of synapses, you need to have that support. And again, that balance changes for many of us as we age, especially if we are ApoE4 positive. ApoE4 gives you an advantage in that you have a hair trigger, essentially, for inflammation. You are responding. So if you live in a squalid environment like the Chimane Indians that Professor Tuck Finch studied, for example, or the Ghana tribe that Tuck also has studied, you are in better shape if you're ApoE4 positive. But if you're not living in a pro-inflammatory, in an environment that's parasitic, then in fact, you have this chronic inflammation that, again, good for when you're fighting things, good for if you step on a nail, good for situations that should be pro-inflammatory, but in the long run, counterproductive. So, you know, as you know, this is, you know, this is so-called antagonistic pleiotropy. This is something that can help you when you're young, but actually can put you at risk for diseases that will shorten your lifespan. And typically, cerebrovascular disease, of course, Alzheimer's disease. And as you know, APOE4 is actually underrepresented in centenarians. So it has been a short-gevity gene, as it were. Again, that is changing and can change by understanding what's actually being driven by this. So we want to know all those markers and those for the type two. And then, of course, we want to know the markers for type three. So we want to know if there are specific toxins and especially mycotoxins. So the toxins can be metallotoxins like mercury, relatively common one. They can be organic toxins like DDE, things like that. They can be biotoxins like trichothesines, ocratoxin A, aflatoxin, gliotoxin. These are toxins produced by various mold species like stachybotrys and aspergillus and penicillium, which are literally fighting us. I mean, they're literally saying, okay, I'm fighting back. For example, one of the responses has been when you have mold growing on treated wood, they're recognizing something's changed. Mold that had been treated with fungicide. So these are things where just as we're seeing increasingly bacteria that are antibiotic resistant, as Professor Shoemaker has pointed out, Dr. Richie Shoemaker, who's done so much work over the years on mold and mycotoxins and described what he calls SIRS, chronic inflammatory response syndrome. As we've had fungicides, as we've had buildings with leaks where we haven't recognized the danger from these, in fact, we've had more and more of this mold-related illness. So we want to know all those things for the type threes. And then, of course, we also want to know if you have a history of head trauma. We want to know if you have vascular compromise. All of those things are critical. Now, you mentioned the diet. So yes, we want to start with the basics. But again, ultimately, it's a program that is customized to you based on what's actually causing your cognitive decline or your risk for cognitive decline. And so the nutritional part we call Ketoflex 12 slash 3. And it's for a very simple reason. So keto, so we want people to be in mild ketosis because that actually turns out to work better for cognition. And many people do better with their cognitive decline, just as Mary Newport showed, of course, with using coconut oil. And that may or may not be the best way to do it for some people. Other people like caprylic acid, MCT oil. Other people are very good at generating endogenous ketones, which if you can do it, is the best way to do it. And so we want to drive you into mild ketosis, which means a very low carbohydrate, high fat, good fats, diet things like avocados and nuts and seeds and things like that. And there is a caveat for people who are ApoE4 and a caveat for people who have very low BMI. So we can talk about that. The next piece is flexitarian. So you can be a meat eater or not. In general, we see meat as a condiment. But again, as we evolved, we tended to eat relatively small amounts of meat, but that's fine. If you do, if it's going to be chicken, it should be pastured chicken. If it's going to be beef, it should be grass-fed beef. Going to have fish, great. Make sure it's wild-caught, not farmed fish. You don't want to have the fish with high mercury. Those are the large-mouthed, long-lived fish, tuna, shark, swordfish, things like that. You want to stay away from those because they can contribute to your cognitive decline. In fact, one of the people who called me a couple of years ago was a very successful businessman who had early Alzheimer's, had already had PET scan proven, and they told him, come back in a year because you're not doing that badly yet. You're still in the MCI phase, but you could already see the signature of Alzheimer's on his PET scan. And when I listened to his story, I said, you've got type 3, and you need to find out if you've got exposure to any toxins. And he said, no, no, everything's great. Well, it turned out that he was eating large amounts of tuna sushi. And he happened to be genetically a poor excreter of mercury, also happened to have some dental amalgams. So he had extremely high organic mercury from the seafood, extremely high inorganic mercury from the amalgams, and then as well, so he had the perfect storm. And his mercury is actually seven times the 95th percentile for our country, just massive, massive mercury exposure. And he's done well with removing that. So we want to know those specific ones. And again, for fish, you want to think about the smash fish. And my wife, who's a family practitioner, reminds me about this, salmon, mackerel, anchovies, sardines, and herring. And she's a real expert on the nutritional side and on the integrative medicine side. She told me 25 years ago, whatever you guys come up with in the lab, in your test tube, I spent my whole career looking at what is driving the molecular signaling that leads to neurodegeneration. She said, whatever you come up with, it's going to have something to do with what you're eating and your exercise. And I said, no, no, no, it's going to be one domain of one molecule, and we're going to get a drug for that thing, and it's going to be over."

Alzheimer Prevention Discussion

With Alzheimer's, there are dozens of things that can be contributing.

"With Alzheimer's, there are dozens of things that can be contributing. And so what we want to do is address all of those."

Ketogenic Diet Discussion

As we've had fungicides, as we've had buildings with leaks where we haven't recognized the danger from these, in fact, we've had more and more of this mold-related illness.

"With Alzheimer's, there are dozens of things that can be contributing. And so what we want to do is address all of those. Yes, if you have pathogens, many people have, for example, Borrelia from Lyme disease or a Lyme co-infection like Bartonella or Babesia or Ehrlichia, things like that, then those need to be addressed. And of course, you need to change the underlying biochemistry. So as you indicated, there are specific biomarkers. So we want to know your HSCRP. It's a marker of inflammation, of course. We want to know your homocysteine, the marker of methylation. If you're not methylating appropriately and your homocysteine is high, then you are at increased risk for neurodegeneration. And of course, it's been published that you have a more rapid decline in your cerebral gray matter volume and hippocampal volume if you have a high homocysteine. Is that because of vascular reasons? What's the homocysteine? The publication did not distinguish. It just simply followed people over years and looked at the rapidity of the decline in volume and could show that not only was it more... Literally, you could put the rapidity of it on a graph with homocysteine and it fit very nicely. But then if you improved the homocysteine and brought it back to normal, they were looking at less than 7 as being normal, not less than 13, which is often used in labs. Less than 7. 7 as being normal. Then, in fact, what happened was people actually stopped their decline and leveled off. So it's suggested that this is a causal relationship, that it is a mediator of cognitive, well, of change in cerebral volume as well as cognitive type. Independent of other biomarkers? Independent of other biomarkers, yes. Wow. So we want to know that. We want to know whether you have glycotoxicity. So we want to know what is your fasting insulin. And again, people will accept it way off the scale. We have an unfortunate situation where classically we have accepted laboratory values as within normal limits, W and L, very arbitrarily as being within two standard deviations of the mean. That actually makes no sense physiologically. It just says that there's a distribution there. It doesn't say that that's optimal for your health. So we'd like to know what your fasting insulin is, and optimally it would be less than five or less than five. Although, again, within normal it goes much higher than that. We'd like to know your hemoglobin A1c, which again is a marker of your, essentially over the last two months, your serum glucose. We'd like to know your fasting glucose. These three actually give you quite complementary pieces of information, all related to this type 1.5 that I mentioned, the glycotoxic type. And then the atrophic, as you can imagine, there are lots of things. We want to know your vitamin D. And again, we want to see that it's optimal, not suboptimal, but within normal limits. We want to know your pregnenolone, progesterone, estradiol, testosterone, free T3. Now, we'd like to know your brain-derived neurotrophic factor and your NGF. There's no simple way on a clinical lab test today to get those. So you have to infer them from other things. What is your hippocampal volume? What have you been doing? If you change these various things we've been talking about, you're likely to have a decrease. Have you been exercising? If you're not exercising, your BDNF is likely to be lower. So we want to look at all of the trophic support for your brain because these are critical things. If you're going to make and keep a large network of synapses, you need to have that support. And again, that balance changes for many of us as we age, especially if we are ApoE4 positive. ApoE4 gives you an advantage in that you have a hair trigger, essentially, for inflammation. You are responding. So if you live in a squalid environment like the Chimane Indians that Professor Tuck Finch studied, for example, or the Ghana tribe that Tuck also has studied, you are in better shape if you're ApoE4 positive. But if you're not living in a pro-inflammatory, in an environment that's parasitic, then in fact, you have this chronic inflammation that, again, good for when you're fighting things, good for if you step on a nail, good for situations that should be pro-inflammatory, but in the long run, counterproductive. So, you know, as you know, this is, you know, this is so-called antagonistic pleiotropy. This is something that can help you when you're young, but actually can put you at risk for diseases that will shorten your lifespan. And typically, cerebrovascular disease, of course, Alzheimer's disease. And as you know, APOE4 is actually underrepresented in centenarians. So it has been a short-gevity gene, as it were. Again, that is changing and can change by understanding what's actually being driven by this. So we want to know all those markers and those for the type two. And then, of course, we want to know the markers for type three. So we want to know if there are specific toxins and especially mycotoxins. So the toxins can be metallotoxins like mercury, relatively common one. They can be organic toxins like DDE, things like that. They can be biotoxins like trichothesines, ocratoxin A, aflatoxin, gliotoxin. These are toxins produced by various mold species like stachybotrys and aspergillus and penicillium, which are literally fighting us. I mean, they're literally saying, okay, I'm fighting back. For example, one of the responses has been when you have mold growing on treated wood, they're recognizing something's changed. Mold that had been treated with fungicide. So these are things where just as we're seeing increasingly bacteria that are antibiotic resistant, as Professor Shoemaker has pointed out, Dr. Richie Shoemaker, who's done so much work over the years on mold and mycotoxins and described what he calls SIRS, chronic inflammatory response syndrome. As we've had fungicides, as we've had buildings with leaks where we haven't recognized the danger from these, in fact, we've had more and more of this mold-related illness. So we want to know all those things for the type threes. And then, of course, we also want to know if you have a history of head trauma. We want to know if you have vascular compromise. All of those things are critical. Now, you mentioned the diet. So yes, we want to start with the basics. But again, ultimately, it's a program that is customized to you based on what's actually causing your cognitive decline or your risk for cognitive decline. And so the nutritional part we call Ketoflex 12 slash 3. And it's for a very simple reason. So keto, so we want people to be in mild ketosis because that actually turns out to work better for cognition. And many people do better with their cognitive decline, just as Mary Newport showed, of course, with using coconut oil. And that may or may not be the best way to do it for some people. Other people like caprylic acid, MCT oil. Other people are very good at generating endogenous ketones, which if you can do it, is the best way to do it. And so we want to drive you into mild ketosis, which means a very low carbohydrate, high fat, good fats, diet things like avocados and nuts and seeds and things like that. And there is a caveat for people who are ApoE4 and a caveat for people who have very low BMI. So we can talk about that. The next piece is flexitarian. So you can be a meat eater or not. In general, we see meat as a condiment. But again, as we evolved, we tended to eat relatively small amounts of meat, but that's fine. If you do, if it's going to be chicken, it should be pastured chicken. If it's going to be beef, it should be grass-fed beef. Going to have fish, great. Make sure it's wild-caught, not farmed fish. You don't want to have the fish with high mercury. Those are the large-mouthed, long-lived fish, tuna, shark, swordfish, things like that. You want to stay away from those because they can contribute to your cognitive decline. In fact, one of the people who called me a couple of years ago was a very successful businessman who had early Alzheimer's, had already had PET scan proven, and they told him, come back in a year because you're not doing that badly yet. You're still in the MCI phase, but you could already see the signature of Alzheimer's on his PET scan. And when I listened to his story, I said, you've got type 3, and you need to find out if you've got exposure to any toxins. And he said, no, no, everything's great. Well, it turned out that he was eating large amounts of tuna sushi. And he happened to be genetically a poor excreter of mercury, also happened to have some dental amalgams. So he had extremely high organic mercury from the seafood, extremely high inorganic mercury from the amalgams, and then as well, so he had the perfect storm. And his mercury is actually seven times the 95th percentile for our country, just massive, massive mercury exposure. And he's done well with removing that. So we want to know those specific ones. And again, for fish, you want to think about the smash fish. And my wife, who's a family practitioner, reminds me about this, salmon, mackerel, anchovies, sardines, and herring. And she's a real expert on the nutritional side and on the integrative medicine side. She told me 25 years ago, whatever you guys come up with in the lab, in your test tube, I spent my whole career looking at what is driving the molecular signaling that leads to neurodegeneration. She said, whatever you come up with, it's going to have something to do with what you're eating and your exercise. And I said, no, no, no, it's going to be one domain of one molecule, and we're going to get a drug for that thing, and it's going to be over."

Mct Oil Discussion

As we've had fungicides, as we've had buildings with leaks where we haven't recognized the danger from these, in fact, we've had more and more of this mold-related illness.

"With Alzheimer's, there are dozens of things that can be contributing. And so what we want to do is address all of those. Yes, if you have pathogens, many people have, for example, Borrelia from Lyme disease or a Lyme co-infection like Bartonella or Babesia or Ehrlichia, things like that, then those need to be addressed. And of course, you need to change the underlying biochemistry. So as you indicated, there are specific biomarkers. So we want to know your HSCRP. It's a marker of inflammation, of course. We want to know your homocysteine, the marker of methylation. If you're not methylating appropriately and your homocysteine is high, then you are at increased risk for neurodegeneration. And of course, it's been published that you have a more rapid decline in your cerebral gray matter volume and hippocampal volume if you have a high homocysteine. Is that because of vascular reasons? What's the homocysteine? The publication did not distinguish. It just simply followed people over years and looked at the rapidity of the decline in volume and could show that not only was it more... Literally, you could put the rapidity of it on a graph with homocysteine and it fit very nicely. But then if you improved the homocysteine and brought it back to normal, they were looking at less than 7 as being normal, not less than 13, which is often used in labs. Less than 7. 7 as being normal. Then, in fact, what happened was people actually stopped their decline and leveled off. So it's suggested that this is a causal relationship, that it is a mediator of cognitive, well, of change in cerebral volume as well as cognitive type. Independent of other biomarkers? Independent of other biomarkers, yes. Wow. So we want to know that. We want to know whether you have glycotoxicity. So we want to know what is your fasting insulin. And again, people will accept it way off the scale. We have an unfortunate situation where classically we have accepted laboratory values as within normal limits, W and L, very arbitrarily as being within two standard deviations of the mean. That actually makes no sense physiologically. It just says that there's a distribution there. It doesn't say that that's optimal for your health. So we'd like to know what your fasting insulin is, and optimally it would be less than five or less than five. Although, again, within normal it goes much higher than that. We'd like to know your hemoglobin A1c, which again is a marker of your, essentially over the last two months, your serum glucose. We'd like to know your fasting glucose. These three actually give you quite complementary pieces of information, all related to this type 1.5 that I mentioned, the glycotoxic type. And then the atrophic, as you can imagine, there are lots of things. We want to know your vitamin D. And again, we want to see that it's optimal, not suboptimal, but within normal limits. We want to know your pregnenolone, progesterone, estradiol, testosterone, free T3. Now, we'd like to know your brain-derived neurotrophic factor and your NGF. There's no simple way on a clinical lab test today to get those. So you have to infer them from other things. What is your hippocampal volume? What have you been doing? If you change these various things we've been talking about, you're likely to have a decrease. Have you been exercising? If you're not exercising, your BDNF is likely to be lower. So we want to look at all of the trophic support for your brain because these are critical things. If you're going to make and keep a large network of synapses, you need to have that support. And again, that balance changes for many of us as we age, especially if we are ApoE4 positive. ApoE4 gives you an advantage in that you have a hair trigger, essentially, for inflammation. You are responding. So if you live in a squalid environment like the Chimane Indians that Professor Tuck Finch studied, for example, or the Ghana tribe that Tuck also has studied, you are in better shape if you're ApoE4 positive. But if you're not living in a pro-inflammatory, in an environment that's parasitic, then in fact, you have this chronic inflammation that, again, good for when you're fighting things, good for if you step on a nail, good for situations that should be pro-inflammatory, but in the long run, counterproductive. So, you know, as you know, this is, you know, this is so-called antagonistic pleiotropy. This is something that can help you when you're young, but actually can put you at risk for diseases that will shorten your lifespan. And typically, cerebrovascular disease, of course, Alzheimer's disease. And as you know, APOE4 is actually underrepresented in centenarians. So it has been a short-gevity gene, as it were. Again, that is changing and can change by understanding what's actually being driven by this. So we want to know all those markers and those for the type two. And then, of course, we want to know the markers for type three. So we want to know if there are specific toxins and especially mycotoxins. So the toxins can be metallotoxins like mercury, relatively common one. They can be organic toxins like DDE, things like that. They can be biotoxins like trichothesines, ocratoxin A, aflatoxin, gliotoxin. These are toxins produced by various mold species like stachybotrys and aspergillus and penicillium, which are literally fighting us. I mean, they're literally saying, okay, I'm fighting back. For example, one of the responses has been when you have mold growing on treated wood, they're recognizing something's changed. Mold that had been treated with fungicide. So these are things where just as we're seeing increasingly bacteria that are antibiotic resistant, as Professor Shoemaker has pointed out, Dr. Richie Shoemaker, who's done so much work over the years on mold and mycotoxins and described what he calls SIRS, chronic inflammatory response syndrome. As we've had fungicides, as we've had buildings with leaks where we haven't recognized the danger from these, in fact, we've had more and more of this mold-related illness. So we want to know all those things for the type threes. And then, of course, we also want to know if you have a history of head trauma. We want to know if you have vascular compromise. All of those things are critical. Now, you mentioned the diet. So yes, we want to start with the basics. But again, ultimately, it's a program that is customized to you based on what's actually causing your cognitive decline or your risk for cognitive decline. And so the nutritional part we call Ketoflex 12 slash 3. And it's for a very simple reason. So keto, so we want people to be in mild ketosis because that actually turns out to work better for cognition. And many people do better with their cognitive decline, just as Mary Newport showed, of course, with using coconut oil. And that may or may not be the best way to do it for some people. Other people like caprylic acid, MCT oil. Other people are very good at generating endogenous ketones, which if you can do it, is the best way to do it. And so we want to drive you into mild ketosis, which means a very low carbohydrate, high fat, good fats, diet things like avocados and nuts and seeds and things like that. And there is a caveat for people who are ApoE4 and a caveat for people who have very low BMI. So we can talk about that. The next piece is flexitarian. So you can be a meat eater or not. In general, we see meat as a condiment. But again, as we evolved, we tended to eat relatively small amounts of meat, but that's fine. If you do, if it's going to be chicken, it should be pastured chicken. If it's going to be beef, it should be grass-fed beef. Going to have fish, great. Make sure it's wild-caught, not farmed fish. You don't want to have the fish with high mercury. Those are the large-mouthed, long-lived fish, tuna, shark, swordfish, things like that. You want to stay away from those because they can contribute to your cognitive decline. In fact, one of the people who called me a couple of years ago was a very successful businessman who had early Alzheimer's, had already had PET scan proven, and they told him, come back in a year because you're not doing that badly yet. You're still in the MCI phase, but you could already see the signature of Alzheimer's on his PET scan. And when I listened to his story, I said, you've got type 3, and you need to find out if you've got exposure to any toxins. And he said, no, no, everything's great. Well, it turned out that he was eating large amounts of tuna sushi. And he happened to be genetically a poor excreter of mercury, also happened to have some dental amalgams. So he had extremely high organic mercury from the seafood, extremely high inorganic mercury from the amalgams, and then as well, so he had the perfect storm. And his mercury is actually seven times the 95th percentile for our country, just massive, massive mercury exposure. And he's done well with removing that. So we want to know those specific ones. And again, for fish, you want to think about the smash fish. And my wife, who's a family practitioner, reminds me about this, salmon, mackerel, anchovies, sardines, and herring. And she's a real expert on the nutritional side and on the integrative medicine side. She told me 25 years ago, whatever you guys come up with in the lab, in your test tube, I spent my whole career looking at what is driving the molecular signaling that leads to neurodegeneration. She said, whatever you come up with, it's going to have something to do with what you're eating and your exercise. And I said, no, no, no, it's going to be one domain of one molecule, and we're going to get a drug for that thing, and it's going to be over."

Alzheimer Prevention Discussion

You follow your LDL particle number, your LDLP. You want to keep it below 1,000.

"And of course, I should have listened to her 25 years ago, but she was right. It does have to do with programmatics, not monotherapeutics. So then the 12-3 part of Ketoflex 12-3, a minimum of 12-hour fast between when you finish dinner and when you start breakfast or brunch or lunch. If you are ApoE4 positive, you're actually a better fat absorber, as you know. So you want to make that 14 to 16 hours. If you're ApoE4 negative, 12 to 14 hours. And be careful, if you have a very low BMI, you can lose weight on this Ketoflex 12-3 diet. And so you have to liberalize typically once a week, have some sweet potatoes or something that's a little more carbohydrate related. And of course, in the book, we talk about the various things that you want to do with this diet. But 12 hours, that gives you time for autophagy. It gives you time essentially at night to induce your ketosis, to clean out your brain. Of course, the glymphatic system, you actually have a change in the architecture of your brain as you're sleeping. You're actually essentially sweeping this stuff out. It's kind of amazing, actually. And so if you're eating with these very small windows of sleep and very small windows of fasting, you're actually doing yourself harm and putting yourself at greater risk. And then similarly, you want three hours before bed after you finish your dinner. You don't want to eat right up until bedtime because your insulin's high. And again, that's hurting your cognition. That's, again, giving you the same sort of insulin resistance problem, storing fat. You're doing all the things that are not helpful. So that's the dietary approach. And of course, you want to have organic. There are toxins in our food. It's unfortunate. We've got a tremendous lifelong exposure to toxins. Of course, Bruce Ames, with whom you trained, developed the Ames test, which allows us now to look at carcinogens. But nobody has ever told us, well, hey, what about dementogens? You're exposed every day to various dementogens, things like mercury, things like some of the organics that are in some of the health and beauty aids, and things like biotoxins. If you're living in a home that has leaks, you are exposed to dementogens, and you need to know about that. So that's the KetoFlex 12-3. It's a plant-rich diet. Mark Hyman called plant-rich as opposed to plant-based. But either way, it is a plant-rich diet that can use some animal products. It's up to you. You want to be vegetarian, that's fine. You don't, that's fine too. That minimizes the toxins. You want to have a high, typically 70% or so calories from fat. And you can start out with using things like MCT oil or coconut oil to get your ketones up. We're finding that people who have higher ketone levels, 1.5 millimolar to 4 millimolar beta-hydroxybutyrate, tend to do better than those who are down lower. ApoE4 positive or negative. ApoE4 positive or negative. Now, interestingly, for the ApoE4s, what we typically suggest, and this was actually originally suggested by Julie G., who started the website, ApoE4.info, you essentially start with using the MCT oil to help you get your ketosis, but then switch after a month or two to more monounsaturates and polyunsaturates. Now you can essentially balance. So you have the best of both worlds. You follow your LDL particle number, your LDLP. You want to keep it below 1,000. So you can adjust how much MCT oil and how much of the monounsaturates and polyunsaturates so that you have the best heart outcome, the best cardiovascular outcome, at the same time have the best cognitive outcome. Be careful. If you don't get your ketones up and you get your carbs down, you're starving your brain. And so then people will say, my gosh, I just have no energy. So you want to use that. You want to basically be changing over to a more ketone-based metabolism for your brain. And then, as you indicated, you want to go back more toward the monounsaturated and polyunsaturated to make it heart healthy. So for the APOE4 positive people, you do recommend lowering the saturated fat intake because of the LDL? After you get...yeah, after you become insulin sensitive. So after you want to drive yourself into insulin sensitivity, so you're able now to convert. So because it takes a few weeks, as you know, to convert from a largely carbohydrate-based metabolism to a largely fat-based metabolism. So if you try to do it in a day, you may end up with so-called keto flu. It takes some time, and you're now producing...it's a whole set of things. You're producing...it's going to be less inflammatory. You're lowering your reliance on glucose. You're becoming metabolically flexible. And you're now essentially developing a use of the ketones. And it just takes a few weeks. It's helpful to do things like exercise and things at that time to help you convert. And then the fasting, overnight fasting of at least 12 hours is... or like you said, if you're 8.4 positive, possibly even increase that to 14 hours. That's interesting that you're talking about, you know, while you're sort of transitioning into the becoming more ketogenic, that you may actually have to increase your saturated fat intake because you have to really... It is kind of hard to go into ketosis without really just having a lot of fat. That's right. And so it's something I have not experimented with yet. You know, I found out I had an APOE4 allele, and so I've definitely become extremely interested in Alzheimer's disease and what I can do to prevent it. Because as you mentioned, you know, not everyone with one APOE4 gets Alzheimer's disease. It's a very complex diet-lifestyle interaction. And no one should. And that's the key. This should be largely ended with the current generation. Everybody should get checked. Everybody should get an optimal personalized program. That is the medicine of the 21st century. I wanted to ask you about this because...so a colleague of yours, Dr. Eric Verdin at the Buck Institute, I spoke with him a few months back on a very interesting paper he had published. I believe it was Cell Metabolism, where he had given animals a cyclic ketogenic diet. And there was just improvement in health span in general. But what was really, really robust was the improvements in cognitive function and brain aging, where it was just hands down clear that that diet really helped delay brain aging. And so, of course, those weren't APOE4 positive mice, but... But this is the exact same thing we're seeing with people, and especially people with early cognitive decline. Now, as you go later and later, it's more and more difficult, but we have seen people even with MOCA scores of zero show improvement. So yes, I think the work that you quoted supports that notion that in fact having ketones is actually quite helpful for cognition. Do you think, and here's a couple of questions related to that, and that is, is that probably multiple things, but one, because you're obviously going to have improved insulin sensitivity. You're not going to have high blood glucose levels and all the inflammatory processes associated with that. Also, the ketones, as you mentioned, are used by the brain quite nicely. And interestingly, it actually spares...are you familiar with the glucose sparing? What happens with the...yeah, so glucose gets spared to make NADPH, a precursor for glutathione, so that helps repair damage. But I'm wondering, if people, like myself, I don't really practice a ketogenic diet, but I also don't. I eat a very healthy diet. I definitely try to make sure I don't eat anything refined, no refined carbohydrates or processed foods or things like that. Right. But the thing is that my fasting insulin is really good and my blood glucose and all that's really good. So for me, going on a ketogenic diet, do you think there would still be more benefit even though the whole insulin sensitivity thing, maybe it would still improve? I'm not sure."

Big 6 Lymphatic Discussion

It does contribute to chronic inflammatory conditions like arthritis and like cognitive decline. In your case, of course, as you indicated, you're interested in prevention because you already know that you're ApoE4 positive.

"So many people, I mean, this wasn't even known as a problem when I was in medical school, but it's become very clear that it's very common. It does contribute to chronic inflammatory conditions like arthritis and like cognitive decline."

Alzheimer Prevention: Prevention

It does contribute to chronic inflammatory conditions like arthritis and like cognitive decline. In your case, of course, as you indicated, you're interested in prevention because you already know that you're ApoE4 positive.

"So many people, I mean, this wasn't even known as a problem when I was in medical school, but it's become very clear that it's very common. It does contribute to chronic inflammatory conditions like arthritis and like cognitive decline."

Protein Aggregation: Protocol

It does contribute to chronic inflammatory conditions like arthritis and like cognitive decline. In your case, of course, as you indicated, you're interested in prevention because you already know that you're ApoE4 positive.

"So many people, I mean, this wasn't even known as a problem when I was in medical school, but it's become very clear that it's very common. It does contribute to chronic inflammatory conditions like arthritis and like cognitive decline."

Sauna: Protocol

The last thing I kind of wanted to mention, just because I wanted you to know about it in case you weren't aware of it, there's some really interesting research coming out of Finland.

"Are you familiar with the saunas? Of course. Oh, okay. Of course, yeah. Dramatic effects. Yes, very interesting. It fits very beautifully with everything we've been talking about."

Gut Microbiome: Diet

Getting your hemoglobin A1C down, yeah, all those things. Getting on a plant-based...

"You know, the quantified self is becoming more and more popular and more and more common. And it's something, to some extent, the responsibility for our longevity and for our health is resting more and more with us. If you want to learn more about the protocol, please go take a look at the book. It's called The End of Alzheimer's from Random House. The other thing you can do is you can go to the website, drbredesen.com, look at it there. and we are responding to there are a lot of comments on the first book that is coming out now in 26 different languages, a lot of comments saying we want more specifics about, you know, what URLs do we use? Where do we go? So we're actually now putting that in a second book that will be out next year. Excellent. Well, thank you so much for this conversation, Dr. Bredesen, for your wonderful research. Yeah, thanks very much, and good luck with your work. Thank you. Hey, guys, you made it all the way through. Thanks for listening, and a huge thanks to Dr. Bredesen for coming on. To learn more about Dr. Bredesen's work, even information on how to actually get a baseline cognoscopy, or how to become a practitioner if you're a healthcare professional, head over to drbredesen.com. That's D-R-b-r-e-d-e-s-e-n.com. Have you taken a consumer-available genetic test like those offered by companies like 23andMe? You can run the APOE report on my website. The APOE report is one of the basic reports, which is just another way of saying free. So make sure to check that out at foundmyfitness.com forward slash genetics. That's foundmyfitness.com forward slash G-E-N-E-T-I-C-S genetics. Finally, does this podcast and its lineup of guests knock your freaking socks off? Hug a supporter today. Thanks to the generous monthly support of people just like you. Yes, the kind of person that even listens to these kinds of episodes, which let's face it, aren't for everyone, that I can even do this. And not only just record the interviews, but take the time to provide extra resources with every episode that many of you may enjoy right on my website. Yes, you too can be a part of the community of outstanding individuals that nurture the very existence of this podcast by making a pay what you can pledge. In other words, whatever you want at foundmyfitness.com forward slash crowd sponsor. That's foundmyfitness.com forward slash C-R-O-W-D-S-P-O-N-S-O-R, crowd sponsor."

Alzheimer Prevention: Protocol

Getting your hemoglobin A1C down, yeah, all those things. Getting on a plant-based...

"You know, the quantified self is becoming more and more popular and more and more common. And it's something, to some extent, the responsibility for our longevity and for our health is resting more and more with us. If you want to learn more about the protocol, please go take a look at the book. It's called The End of Alzheimer's from Random House. The other thing you can do is you can go to the website, drbredesen.com, look at it there. and we are responding to there are a lot of comments on the first book that is coming out now in 26 different languages, a lot of comments saying we want more specifics about, you know, what URLs do we use? Where do we go? So we're actually now putting that in a second book that will be out next year. Excellent. Well, thank you so much for this conversation, Dr. Bredesen, for your wonderful research. Yeah, thanks very much, and good luck with your work. Thank you. Hey, guys, you made it all the way through. Thanks for listening, and a huge thanks to Dr. Bredesen for coming on. To learn more about Dr. Bredesen's work, even information on how to actually get a baseline cognoscopy, or how to become a practitioner if you're a healthcare professional, head over to drbredesen.com. That's D-R-b-r-e-d-e-s-e-n.com. Have you taken a consumer-available genetic test like those offered by companies like 23andMe? You can run the APOE report on my website. The APOE report is one of the basic reports, which is just another way of saying free. So make sure to check that out at foundmyfitness.com forward slash genetics. That's foundmyfitness.com forward slash G-E-N-E-T-I-C-S genetics. Finally, does this podcast and its lineup of guests knock your freaking socks off? Hug a supporter today. Thanks to the generous monthly support of people just like you. Yes, the kind of person that even listens to these kinds of episodes, which let's face it, aren't for everyone, that I can even do this. And not only just record the interviews, but take the time to provide extra resources with every episode that many of you may enjoy right on my website. Yes, you too can be a part of the community of outstanding individuals that nurture the very existence of this podcast by making a pay what you can pledge. In other words, whatever you want at foundmyfitness.com forward slash crowd sponsor. That's foundmyfitness.com forward slash C-R-O-W-D-S-P-O-N-S-O-R, crowd sponsor."