hi, i’m dr. mark hyman. welcome to the fat summit...

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The Future of Alzheimer’s Disease Guest: Dr. Dale Bredesen

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Dr. Hyman: Hi, I’m Dr. Mark Hyman. Welcome to The Fat Summit where we separate fat from fiction. I’m so glad to be here with Dr. Dale Bredesen who is a renowned neuroscientist and neurologist who studied Alzheimer’s for most of his career looking at the basic mechanisms. How do we get Alzheimer’s? And he has really done the hard work in the lab, finding out what’s going on. Has been a pioneer in this area. But you know what? He discovered that, like everybody else, many of the ways we’ve been looking at Alzheimer’s just don’t make sense. We’ve done hundreds of studies, spent billions of dollars. And found really nothing that works to prevent or reverse or really treat Alzheimer’s. So he began to reconsider this whole model. And he’s now the founder and the CEO of the Buck Institute on Aging and is doing really the hard work of putting together the story of how we get Alzheimer’s, how we get dementia. And what we can do about it, which is pretty unique and groundbreaking. And I encourage anybody who’s at all concerned about their brain to check out his work. So welcome, Dr. Dale Bredesen, to The Fat Summit. Thanks for being here! Dr. Bredesen: Great. Thanks very much, Mark! Dr. Hyman: So, Dale, we’re here in Omega Institute teaching a conference on

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reversing dementia, which seems like an oxymoron. They shouldn’t go in the same sentence, “reversing and dementia.” And yet, here we are talking about this. And today, you gave an astounding lecture where you showed a video, which is going to be a documentary soon to come out May of 2017, showing case after case after case of people who had documented cases through PET scanning, through neurocognitive testing of dementia that then implemented a program that we’re going to talk about in a minute that reversed their dementia. And it was so dramatic that the neuroradiologist who looked at the scans said, “This must be wrong. You know, I’ve seen 75,000 scans. And I’ve never seen this before. I must have gotten it wrong.” And then, you sent it to another neuroradiologist. And they found the same thing. And they still couldn’t believe it. And they tried to explain it away because it just didn’t make sense. And yet, this is what we’re seeing. So this is really revolutionary. This is not just an incremental improvement in a slight reduction in heart disease or a slight reversal of some disease. This is a groundbreaking moment in history where we’re actually, for the first time understanding the nature of dementia and Alzheimer’s. And you figured it out how to put all this… Tell us how you went from being a reductionist neuroscientist in the lab studying the mechanisms of Alzheimer’s to taking a step back and looking at the macro lens at the 30,000-foot level and trying to figure out how to put all the pieces together. Dr. Bredesen: Well, thanks very much, Mark. Yeah. So we have been looking for 27 years’ now in the laboratory. So we’ve been a little slow. It’s a long time. And looking at what are the drivers? What actually drives the phenomenon of neurodegeneration? Why does this happen in your brain? And why do you get the pathology and pathophysiology that you do see? And what we found was surprising. What we found, first of all, was that organisms make amyloid. The amyloid that you find in the brain. Dr. Hyman: And that’s the sticky stuff that gets in the Alzheimer’s brains. It covers it and makes it not work. Dr. Bredesen: Exactly. And it’s the stuff that everybody wants to get rid of. Well, what we found is it’s actually a protective response to three fundamentally different things. You get it because of inflammation, whether it’s infectious or sterile inflammation. You get it because of trophic factor withdrawal, whether it’s vitamin D. Whether it’s nerve-growth factors—


Dr. Hyman: Things that make the brain grow and be functioning. Dr. Bredesen: Things that are there for support. If you suddenly drop someone’s estradiol level to zero overnight, they will have a downsizing event that features the amyloid. And on the other hand, you also see it because it binds toxins. So this is actually, what we call Alzheimer’s disease, is really a pathology that is associated with a protective, not destructive response, protective response to these different things. Dr. Hyman: To all sorts of insults— Dr. Bredesen: All sorts of insults. Dr. Hyman: it’s not just one thing. Dr. Bredesen: Exactly. It’s those three major areas. Dr. Hyman: There’s no such thing as Alzheimer’s. It’s not a uniformed disease. It’s got multiple ways of being caused. But it all results in the same pathology. Dr. Bredesen: It results in similar pathology. Exactly right. So the idea is, if you’re going to get rid of the amyloid, you’d better first find out what’s causing it because if you just get rid of the amyloid without understanding what’s causing it, you may actually be missing that protective piece. And then, when we looked at the molecular biology, what actually drives the parent molecule that gives you the amyloid—the amyloid’s a little snippet that comes from a much bigger piece—what it turned out was that this is literally a molecular switch. It is a molecule that, if it’s cut at one site, gives you two peptides, two results from the-- Dr. Hyman: Two proteins, basically. Dr. Bredesen: Two pieces of protein that are actually supporting your brain causing neurite outgrowth, synaptic production, synaptic maintenance, literally causing memory. On the other hand, if you take that same molecule and you cut it at three different sites, you now have four peptides that are doing just the opposite. They’re called causing pulling back, lost of the synapsis, reorganization, activation of programmed cell death. These are all pro Alz. So there’s literally a pro Alzheimer’s side. And there’s an anti-Alzheimer’s side.


And so when you look at what is driving at one side or another, it’s all the things that you knew about from functional medicine. All the things that you knew about from the epidemiology. So everything from your vitamin D level to how much NF-kappa B activation there is. How much inflammation is going on? What’s your metal homeostasis? What’s your testosterone level? You can go on and on. So we started looking at all the mechanisms. And we initially identified 36. So what we told people is, “Look— Dr. Hyman: Now, there’s like 54, right? Dr. Bredesen: Yeah, now, there’s more. Yeah, and there’ll probably be more. But what we found originally is it’s a little bit like telling people, “Look, you’ve got 36 holes in your roof. If you’re going to seal one of them, it’s not going to help you. The floor is going to be pretty wet the next day if it rains anyway.” Dr. Hyman: Even if you do 10, you’ve got to do all 36. Dr. Bredesen: Exactly, so you’ve got to do as many as you can. And it turned out straight from the test tube right to what functional medicine has been suggesting, and what you’ve been talking about since your book in 2007, very similar stories. And I think we’re seeing somewhat similar results. People who were, especially, in the early stages of dementia doing extremely well, very well documented with increases in hippocampal volume. We just actually published this paper about two weeks ago showing unprecedented increases in hippocampal volume and— Dr. Hyman: So wait a minute. So what you’re saying is that if you employ this program with patients, that their brains literally grow back—that the memory centers grow back—and this has never been done before? Dr. Bredesen: So there have been some suggestions in the past of modest increases in hippocampal volume with things like exercise. That alone-- Dr. Hyman: And that’s the memory center. Dr. Bredesen: Exactly. And it’s an important region, especially for short-term to long-term consolidation of memory. And it’s an area that’s particularly hard hit in Alzheimer’s disease. So what we’re seeing is that we see increases in volume of the hippocampus. And we also see dramatic improvements in quantitative neuropsychological testing.


Dr. Hyman: Wow! That’s mind blowing-- Dr. Bredesen: So we’re very excited about it. Dr. Hyman: that you actually, literally see the brain grow back when you take away these insults. And then, you provide what you call these trophic factors. These like fertilizers for the brain like hormones and nutrients and the right balance of things, it seems to just recover. Dr. Bredesen: Absolutely. Including things like omega-3s and things like resolvins and things like that— Dr. Hyman: But we never knew this, right? I learned in medical school that you’re born with a certain amount of brain cells. That’s it. You get it. If you damage them in college, tough luck. But now, you’re saying, “No, that’s not true.” This is a paradigm shift. Dr. Bredesen: Well, it’s interesting. One of the guys that was treated is a very good internist. And he said himself, when we asked him to go back and get the follow up MRI, he said, “You don’t grow brain back. So there’s no reason to do this.” So we finally convinced him to go get it. He went back and got it. And had a marked increase in his hippocampal volume. So, in fact, as you know, the whole stem cell field, it’s become clear that the brain is a much more dynamic structure. And, of course, with all the neuroplasticity, the production of new synapses, and dendritics sprouting, and all this sort of thing, there is a tremendous amount more plasticity than you and I were taught when we grew up. Dr. Hyman: So one of the things you often talked about, when I hear you talk, is the role of insulin resistance and sugar damaging the brain, also the benefits of fat. So how do we reconcile the advice that we should be lowering saturated fat and we should not be eating a lot of fat, with the fact that you’re finding this action may be therapeutic? Dr. Bredesen: This is a really good point. And obviously, you’ve been preaching the concerns about insulin resistance for years. And what we find is that insulin resistance is one of the most important and one of the most common things we see with Alzheimer’s disease. And what happens is you actually get, both of what we call type 1, the inflammatory type, and type 2, which is the trophic loss type, the atrophic type. With the sugar, you get type


1.5. It’s part 1 and part 2. Why? Because you glycate proteins, leading to some inflammation. So you get the type 1 there. Dr. Hyman: It’s like crème brûlée in the brain, right? Dr. Bredesen: Exactly. Exactly right. And then, you also have atrophic loss because now what you’ve done is you’ve actually created insulin resistance. And, in fact, Ed Goetzl from UCSF has done a beautiful study where he’s shown that you can isolate neural exosomes from the blood allowing you to look at brain chemistry. And what he shows is, in fact, that virtually everybody with Alzheimer’s has in the brain the signature of insulin resistance. He looks at specific phosphorylations of IRS-1. Dr. Hyman: It’s like diabetes of the brain. Dr. Bredesen: Exactly. So that’s certainly part of this. And therefore, going along with that, you look at PET scanning. What are you losing? You’re losing glucose utilization, especially in the temporal region and the parietal region. And that is the signature of Alzheimer’s disease, especially in other regions such as posterior cingulate and precuneus. Dr. Hyman: So what you’re saying is you’re not able to take up the sugar in the brain areas because you’re resistant to the insulin, which doesn’t work in the brain. Which means the sugar is higher in the areas because you can’t get rid of it. Is that it? Dr. Bredesen: Yeah, you are not utilizing glucose as you should. And that is a signature, in fact, of Alzheimer’s disease. Dr. Hyman: That’s like the way you diagnose it on the imaging test. Dr. Bredesen: Exactly. Exactly, you look at that and say, “Oh, this person’s got Alzheimer’s disease.” And what are you actually looking at? You’re looking at reduced glucose utilization due to an insulin resistance. Dr. Hyman: So you’re basically looking at diabetes in the brain with these PET scans. Wow! Dr. Bredesen: Exactly. And so what do you do for it? As you said, you give fats and good fats. And, in fact, the switchover, one of the most important pieces in the program is the switchover from carbohydrate metabolism to fat metabolism.


Dr. Hyman: How do you do that? Dr. Bredesen: So, of course, we follow Dr. Hyman’s protocol. So what we try to do obviously is get people to get completely rid of it. And, of course, as you know well, it’s hard for people to get rid of simple carbs. And then, we load them up with good fats. Then, we also encourage things…Well, we include things like omega-3s. If there’s some inflammation there, we also use pre-resolvins, as many others do now. And so we’re— Dr. Hyman: These are extracts from omega-3s, these pro-resolvins, right? Dr. Bredesen: Exactly. Yeah, as is pointed out. But the part that used to be thrown away, which turns out to be much better than people realized. Dr. Hyman: This is from work at Harvard where they— Dr. Bredesen: This is from work from Charlie Serhan of Harvard. Exactly right. Dr. Hyman: And they basically found that within fish oil, there’s this set of compounds that when concentrated can turn off what’s called the inflammasome, which is this systemic inflammatory response. It’s like a master switch, right? Dr. Bredesen: Exactly. So these specialized pro-resolving mediators, as they call them. Things that are critical for allowing you to have that second step. When you have this ongoing inflammation, you need a resolution step. And this involves things called resolvins and maresins and things like that. And so this is you can now give precursors. Thanks to Dr. Serhan, you can now give precursors for those. Dr. Hyman: And what about the ketogenic diet or the MCT oil that you recommend? What about that? Dr. Bredesen: This is a really good point. And we’re finding interestingly subjectively, repeatedly people are telling us, they do the best cognitively when they are mildly ketotic. And we’ve always recommended that people have a minimum of a 12-hour fast between finishing dinner and first food the next day. And a minimum of three hours between finishing, and then, of course, going to bed. And the original idea was we want to induce autophagy. We want to


allow for brain cleansing. As you know, there’s actually a subtle change in the anatomy of the brain that takes place while you are sleeping. Dr. Hyman: It’s like a lymphatic system in the brain that cleans out all the junk. Dr. Bredesen: Exactly. The so-called glymphatic system. So you actually clean out. Exactly right. So we want to induce that. And then, it turns out, of course, the ketosis induction is very helpful, as well. Coconut oil and MCT oil enhance that and, of course, a mildly ketogenic diet. And so a number of people actually get keto meters, measure these. It’s been very helpful. And people do find that their cerebration is actually better with mild ketosis. Dr. Hyman: Yeah. No, I had a patient recently who was doing really well for like seven or eight years. And then, she started to decline. I’m like, “Okay, let’s try this.” And we put her on Bulletproof coffee in the morning. We gave her a very high-fat diet. It was like 70% fat, which seems crazy, and putting butter and saturated fat. And she just woke up and was like Rip Van Winkle. Dr. Bredesen: Yeah. Yeah, it is surprising how helpful that is. And we see the same thing in some people. Very exciting. Dr. Hyman: So what’s the most dramatic story that you could share about a patient who you’ve seen who came in with dementia? And what did you do for them and how did they reverse? Dr. Bredesen: Well, so I can tell you about a guy who is now 71 years old. Came him when he was 69 initially. But he had actually had 11 years at that time of slow decline. And then, what had happened is that he had declined rapidly over the previous 18 months. And he had had a PET scan, which again, showed classic Alzheimer’s signature with temporal parietal, decrease in glucose utilization. He was APOE-4 positive. So the most important genetic risk factor for Alzheimer’s, he does have that, which then puts him at increased risk. And then, he had had sequential neuropsychological quantitative testing, multiple hours each time, showing a very clear monotonic decline, and finally had really just dropped off that eighteen months. And he was down to third percentile on some tests, less than one percentile on other tests. Dr. Hyman: On the neurocognitive testing, it’s just how you measure people’s memory and cognitive functioning.


Dr. Bredesen: Neurocognitive testing. Exactly. And he was to the point where he couldn’t remember who he had lunch with. He was being urged to shut down his companies he had at multiple sites. And he went on the program. He’s now been on it for two years. Came back and did the quantitative testing again. He knew he was better. His wife knew he was better. Dr. Hyman: So what did he do? What did you have him do exactly? Dr. Bredesen: So he went through an entire, very much like what you showed earlier today. Dr. Hyman: Give us some of the nuggets. Dr. Bredesen: Yeah. So we had him again switch over to a more fat-based diet. We had him on several different herbs such as ashwagandha and bacopa, rhodiola. He was also on curcumin. He ended up interestingly becoming much more insulin sensitive. He dropped about 20 pounds. He’s an exercise fiend. This guy does massive bike exercise, swimming, pretty much every day. Dr. Hyman: So they ramped up the exercise. Dr. Bredesen: He also did some brain training. He also did stress reduction. And then, we have people sometimes do a neurophysiological driving, which is called neuroAgility, which we found helpful. And this was designed by a neurophysiologist, basically drives your brain with a certain frequency that seems to be helpful. Some people call it meditation on steroids. Dr. Hyman: What is it, a neurofeedback? Dr. Bredesen: It’s essentially the next version of what used to be called binaural beats. So you actually wear it for about 30 minutes each night. You wear headphones. And this will drive your brain with an appropriate frequency. That’s the idea. So he did all of the above. As I mentioned lost weight and actually slimmed down, became more insulin sensitive. He then went back and had repeat neuropsychological testing. And I was actually called by the guy who did the testing who said in 30 years as a neuropsychologist, he’d never seen such dramatic improvements. So he went, for example, from third percentile to 84th percentile on one test-- Dr. Hyman: In the brain functioning.


Dr. Bredesen: from brain functioning. Dr. Hyman: Amazing. Dr. Bredesen: So just dramatic. Dramatic. Dr. Hyman: You can’t really cheat on that, right? Dr. Bredesen: There’s no placebo effect for those sorts of tests. Dr. Hyman: Yeah. Right. Because you’re actually giving them exercise to do, test to do. And they either can do them or they can’t. Dr. Bredesen: Exactly. Dr. Hyman: And he got better from the first percentile, the third percentile, or the 84th percentile— Dr. Bredesen: 84th in some— Dr. Hyman: which is a lot better than average. Dr. Bredesen: Oh, yeah. So he has gone from barely being able to remember who he had lunch with to performing at a higher level than the vast majority of people. Dr. Hyman: Than 84% of the population. Dr. Bredesen: Exactly. Yeah. Dr. Hyman: Right, That’s stunning. Dr. Bredesen: So, in fact, he had some scores in the 90s, so doing extremely well. And, in fact, instead of shutting down his offices, he’s now opened a new office. Dr. Hyman: Unbelievable. Dr. Bredesen: So yeah. Dr. Hyman: So you’re giving people their life back, where their life was over.


Dr. Bredesen: Well, it’s interesting you should say that. One of the remarks he himself made was he said, “I’ve allowed myself to talk about the future with my grandchildren once again. I had stopped doing that.” So just really heartwarming to hear these success stories. Dr. Hyman: Well, listen, my son went to high school with a kid whose dad got diagnosed with dementia. And he had, I think, heard about my book and then he heard about you. And he went to see you as a patient. And he was going to move to Mexico to go write a book about his descent into darkness. And instead, he recovered. And now, he’s writing a book about his recovery from dementia, which is amazing. Dr. Bredesen: Very exciting. Dr. Hyman: And the thing is look, you’re a renowned neuroscientist. You’re not some quack doctor who’s peddling stuff that just doesn’t make any sense. I’m a bit more of a quack. But I’m at Cleveland Clinic. Dr. Bredesen: Hardly. Hardly. Dr. Hyman: And I’m at Cleveland Clinic. And this is real stuff. This is actually what the future is. And yet, so few doctors know about this. And so few patients know about this. And it’s why both of us work so hard and tirelessly trying to get this out there because we don’t want one more person than has to to have to go through this or suffer if they don’t have to. Dr. Bredesen: Right. And as you know, there are patients who’ve put out their own books on their own improvement. This is being seen by you, by me, by David Perlmutter, by others. This is not something that is one single antidote. This is being seen by multiple people. And, as you know, the common theme has been a functional medicine multifactorial approach. Dr. Hyman: Mmm hmm. Yeah, it’s so exciting. We’re trying to collaborate and doing work together and trying to get research started in Cleveland Clinic and train doctors. This is really the future. So I’m so excited about it. So in terms of the statin issue and cholesterol issue, I’d like to talk a little bit about that. Because when we were at Cleveland Clinic, you gave grand rounds there a few months ago. I think you kicked off the functional medicine grand rounds at Cleveland Clinic. We had like 3,000 people watching on line. I think. And one of the slides you had, this like jumped out at me, which was how statin drugs, which is probably the most widely prescribed medication, seems


to increase amyloid, which is this stuff that coats the brains of people with Alzheimer’s. And I was shocked by that. And I was like, “Wow! This is an explanation of why statins might cause memory loss.” So how strong is the data there? And like, what would you tell people whose doctors are telling them to lower their cholesterol, that it’s bad for their heart, it’s bad for their brain, and they shouldn’t be doing this? Dr. Bredesen: Yeah. Yeah, that’s a great point. So as you know, everyone’s used to hearing about carcinogens. And, of course, Bruce Ames did us all a great favor by developing the Ames test. And we looked. So we’re all used to saying, “Is this a carcinogen? Is that a carcinogen?” Nobody ever tells you about dementigens. Is there something that you’re putting on your hair? Or is there something that you’re eating? Dr. Hyman: Dementigens. I love that! Dr. Bredesen: Well, of course, sugar is a dementigen. We know that, right. Dr. Hyman: Ah, that’s a great term. Dr. Bredesen: Mercury is a dementigen. But we’d like to know. Just like we have a list of carcinogens. We need a list of dementigens. So a number of years ago, we started looking at this balance that we talked about before. The four bad guys-- Dr. Hyman: I talked about a lot of those in my talk today. The things that cause brain damage. Dr. Bredesen: Exactly. Exactly right. So we actually screened every known drug for whether it put you on the wrong side of the curve or the right side of the curve. And the first thing that popped out, as putting you on the wrong side of the curve, was statins. And we actually published that a few years ago. So now-- Dr. Hyman: Statins are dementigens. Dr. Bredesen: They can be dementigens. Now as you know, there is also a well-documented positive effect as an anti-inflammatory effect. Okay. On the other hand, there are other ways to get an anti-inflammatory effect. So the problem we see repeatedly is one, people drive their cholesterols far too up. You need cholesterol for your brain. You don’t want to have a ton of oxidized


cholesterol, fair enough. But you want to have the cholesterol. So people driving their cholesterol’s too low, that’s bad for the brain. And then, secondly, of course, there’s the CoQ issue that you’ve talked about a number of times. So we do find, and no question, there are many people, as you know, who will go on statins and notice major changes in memory. But there are other people— Dr. Hyman: Have you ever APOE4 before. Is that more of a risk to go on a statin? Dr. Bredesen: So well, a part of the problem is that people with APOE4 tend to be put on statins more because they tend to have a high cholesterol. Dr. Hyman: Higher cholesterol. Right. Dr. Bredesen: Exactly. So what we try to do—and again, you have to be very careful, of course, it’s a controversial area—but we encourage people to look at alternative ways to reduce their “bad cholesterol,” certainly. And we argue that they should be looking more at oxidized LDL, as you pointed out earlier, particle number, and not be focused so much on total cholesterol and LDL because that may not be a problem. And again, you want some cholesterol. Otherwise, you’re going to look at brain shrinkage with low cholesterols. Dr. Hyman: Because a lot of the brain is actually comprised of cholesterol. Dr. Bredesen: You need that cholesterol. Absolutely. Dr. Hyman: Yeah, that’s amazing. So if you have a patient who comes in with dementia, do you take them off statins just right off the bat? Dr. Bredesen: We often work with their physicians. Where, of course, we don’t want to tell their cardiologist what to do. So we often with them and say,-- Dr. Hyman: I do. Dr. Bredesen: “Well, you know, is this a possibility?” Yeah. And it’s— Dr. Hyman: I would tell them, “It’s your body. This is what I think. You decide, but.” Dr. Bredesen: Yeah. And we’ve had a number of people go off and who are


much happier and doing better off. Dr. Hyman: Which organ do you want to pick? I guess, right? Dr. Bredesen: Yeah. Well, as you said earlier, you want to be healthy from top to bottom. Dr. Hyman: So saturated fats, this is something that we’ve all been told to reduce, the government tells us to reduce. And yet, in some of your protocols, you’re actually talking about increasing them like the MCT oil and coconut fat. Dr. Bredesen: Yes. Yes. And so we’ve had people say to us, “Wait a minute, you know, you’re telling me to take saturated fats or to take MCT oil or to take coconut oil, and things like that? And we say, “Yes! That’s exactly what we’re telling you.” So we usually say, “You don’t want to do what we call the Berfooda triangle. It’s like the Bermuda triangle. But it’s got food. So you don’t want the Berfooda triangle, which is, as you know, saturated fats, simple carbs, and low fiber. So you combine those three things— Dr. Hyman: Yes, bad news. Dr. Bredesen: bad news, right. So we tell people, “Look, just stay off the simple carbs, keep your fiber good, and absolutely, you’re going to get great brain function from things like MCT oil and coconut oil. Absolutely. Dr. Hyman: I think this is such a huge point. I just want to pause here because I call it sweet fat. If you say saturated fat’s good, then people can hear, “Oh, I’m going to put butter on my bagel. You know, I’m going to have ice cream. I’m going to have doughnuts. I’m going to have French fries.” You cannot eat fat with carbs because if you do, you’re going to get in trouble because you’re increasing insulin. The fat will get stored. It creates inflammation. It’s a bad scene. So the more fiber also means more vegetables and plant foods, lower sugar, and cutting out the starch and the sugar, allows you to eat saturated fat, which has beneficial effects if you’re not eating it with starch and sugar and not enough fiber. In fact, there was a great study by Dr. Walter Willett, where they looked at, I think it was a physician’s health study, where they looked at saturated fat.


And they found that in the context of a low glycemic diet and high fiber, there was no harmful effects of the saturated fat. Dr. Bredesen: And it will also allow you to keep that metabolic flexibility, whereas when you start mixing them, you start to lose that. Dr. Hyman: Yeah. Very important. So what are some of the biggest surprising things you found in switching over your perspective from this reductionist lab scientist to treating these patients? And it’s like, what was the “aha moments,” that you just had that blew your mind? Dr. Bredesen: Yeah, one of them was that I didn’t have to look at fruit flies anymore, which was really nice. But the thing that has been really exciting to me is to see that you can look at different causes. And I have been very surprised to see almost nobody has one cause. Every time we think, “Aha, that’s what it is.” We keep looking. And we find out, “Oh, there’s something else. Oh, there’s something else. Oh, there’s something else.” Most of the people we’re seeing have between 10 and 25 suboptimal metabolic values. I’ve been shocked at how much. And then, the second thing that’s come up is we’re finding that a surprising number of people will have infectious agents associated with it. Dr. Hyman: Mmm hmm. Like? Dr. Bredesen: So it’s everything from P. gingivalis from the mouth-- Dr. Hyman: Gum diseases. Dr. Bredesen: to gum diseases. Exactly. So this is why the oral hygiene issue. Of course, herpes simplex virus, which affects the brain, of course, and another one. So then Lyme disease, mycotoxins and molds, and especially things like Stacybotrus, Penicilllium, Aspergillus, these things. And, of course, things that Ritchie Shoemaker had. His group has spent years looking into. And I’ve been very surprised at how commonly we’re seeing people who have the classic laboratory values. High C4a and high TGF-beta 1, HLA-DR/DQs, all of these things that are associated with mycotoxins. And this seems to be a very common contributor to cognitive change. Dr. Hyman: Yeah, you just unloaded a whole bomb there on us. So help me unpack that for a minute for people who are listening because it’s a big deal what you just said. Half of all buildings in America has some water damage,


which typically results in mold growth, which then results in the release of this whole class of molecules called inflammagens, including mycotoxins and all these things that then cause inflammation in the body. And what you’re saying is that these mold toxins and these inflammagens drive up the immune system in the body that damage the brain. That they’re neurotoxic. Dr. Bredesen: Right. Exactly right. And back in the 1800s, they were called TB consumption, remember this? Dr. Hyman: Yeah. Right. Dr. Bredesen: So this was you would consume, you would lose weight. So I call Alzheimer’s a disease of assumption. People have made all these assumptions. We assume that it’s fine to eat processed foods. We assume that it’s fine to have sugar. We assume that it’s fine to have trans fats. And one of the assumptions we make, why not just build structures. Yeah, you can let some water in. And you get some mold. The fact of the matter is we’re all living in a soup. And for at least 25%, and this is Shoemaker’s work, there is a genetic component where you cannot live in that soup. You don’t do well in that soup. The lab values show it, changes in mentation, often with other things like asthma or changes in ability to go up a flight of stairs, chronic fatigue. All these things can be related to this soup that we live in. That, as you said, has inflammagens in it, volatile organic compounds in it, actinomycetes, various mycotoxins, spores, on and on and on. There are dozens of components in this soup that we live in. And we’ve got to continually be detoxing and responding immunologically. Dr. Hyman: And there’s something, Dale, that most physicians don’t look for, pay attention to, ask you about. And when was the last time your doctor asked you, “Is your house got mold in or have you evaluated?” Because you might not even know. It might not be something you can smell. In fact, I just had my house checked. And I have a lot of mold in my house that I didn’t even know about. And it came from this one room. And it circulates the house. And I don’t really go in that room very often. And I ended up having impact from it. So it was really fascinating to see how common this is and how much…Well, it was fascinating to see you’ve actually identified it with patients who have Alzheimer’s diagnosed, that it seems to trigger this response in the body.


Dr. Bredesen: Exactly right. So we called this inhalational Alzheimer’s disease—IAD—and then published on this earlier this year. And we’ve been shocked at how many people seem to have that phenomenon. Dr. Hyman: So really, you got to cast a broad net when you’re diagnosing someone with Alzheimer’s. You can’t just say, “You have Alzheimer’s.” You’ve got to say, “Well, what kind is it? And what type is it? And what are the factors? And how do we begin to deal with all these 36 different holes or 50 more holes?” Right? Dr. Bredesen: Right. Now, this is very much I think of a functional medicine approach. As you said, “Functional medicine is about asking why?” So instead of just saying, “You have this dementing illness, and we don’t know what causes it, and we don’t think there’s anything to help you with it, we want to get to the root cause. We want to understand why. How did you get here?” And the good news is the molecular biology and the functional medicine have come together in a really nice way to give us the whole waterfront here of, “Here are all the things that are contributing. Now, we know where to look. And we know how to address each one.” Dr. Hyman: So I know you’re coming out with a book on reversing dementia in May of 2017 and a documentary. Which, I’ve seen snips of, which is mind blowing, really looking at the cases of people who’ve recovered. People say like, “I couldn’t remember my combination or I couldn’t remember how to drive anywhere. And all of a sudden now, I just flew to San Francisco. I got in the car and drove to…” See, just mind boggling stories. And I know it’s going to be a lot of great information in there. But I wondered if you could give us five of the biggest things that are dementigens that we should be watching for. And five of the top interventions that you found help people. Dr. Bredesen: Sure. Okay. Dr. Hyman: And if it’s four or three or six, that’s okay. Dr. Bredesen: Yeah. So all right. So let’s talk about dementigens. I would say- Dr. Hyman: These are things you’d want to avoid or deal with. Dr. Bredesen: Things that you want to avoid. Absolutely. And one of them


would be simple carbs. No big surprise. Dr. Hyman: Sugar and starch. Dr. Bredesen: And this is sugar and starch. These things, especially when you’ve got very little fiber in your diet. Big problem. Second thing we see all the time is poor sleep. People, in Western society, it’s something great. It’s a badge of honor. You say, “Yeah, I stayed up all night doing this.” Dr. Hyman: I know. Dr. Bredesen: What did you do when you were an intern resident, right? You stayed up all night. Dr. Hyman: Stayed up all night. Dr. Bredesen: Exactly. I did the same. Dr. Hyman: I just read this article in the New York Times about Obama, who was like sleeps five hours a night because he’s working up late and studying, having alone time. I’m like, “This is not good. You don’t want a President whose sleep deprived and can’t make good decisions.” Dr. Bredesen: Exactly. We want him to take some melatonin and get more sleep at night. Dr. Hyman: That’s right. Dr. Bredesen: Exactly. So sleep has been a big one. Okay. And then, again people having exposure to things like water-damaged buildings. And one of the things we’re finding is people who have chronic sinus problems. You have to remember this is relatively close to your brain. The access through cranial nerve 1 is a big, big issue. And then, of course, another one would be-- Dr. Hyman: It’s a chronic, hidden, latent infections in your sinuses. Dr. Bredesen: Exactly. And we talk about optimizing your gut microbiome. I think there’s going to be a lot in the upcoming years on-- Dr. Hyman: Your nasal microbiome. Dr. Bredesen: Exactly, on optimizing your nasal and sinus microbiome. Not


just about treating MARCoNS, for example, but also about optimizing the flora that are actually there. Dr. Hyman: Yeah, nasal probiotics, that’s next. Dr. Bredesen: Nasal probiotics, that’s going to be the next big thing. Absolutely. Yeah. Dr. Hyman: You heard it here first. Dr. Bredesen: Exactly. Exactly. It’s going to be Dr. Hyman’s Nasal Probiotics. All right. And then, we see people who just have a tremendous amount of stress. And one of the things we see is people will often present after periods of tremendous stress. So we’ll have a lawyer who had a couple of years of the toughest case of his life, up all night, working very hard, and at the end just falls apart. Wins the case. And then, just falls apart. Develops dementia. Those sorts of things. So that would be another one that we see commonly. And then, of course, mercury is another one. And we do see people, both with amalgam related, inorganic, as you’ve talked about, as well as the guy who loves tuna sushi and wants to eat it every day and develops this tremendous amount of organic mercury. And mercury’s been argued to be not an important cause of dementia. Well, for many people, it’s not. But for those people that have high mercury, it’s a very important cause. And the good news is it’s a very treatable cause. So those would be things that I think are some of the most important. And as far as what works— Dr. Hyman: So risks of dementia is sugar and refined starch, not enough fiber. It’s mold and mold in a lot of damaged buildings. It’s chronic sinus or nasal pharyngeal latent infections. It’s mercury and-- Dr. Bredesen: Poor sleep and stress. Dr. Hyman: poor sleep and stress. Dr. Bredesen: Absolutely. Dr. Hyman: Those are all big things. And we can deal with all of them.


Dr. Bredesen: Yeah. And obstructive sleep apnea is another one that contributes sometimes. Dr. Hyman: They’re all treatable. Dr. Bredesen: But these are all things— Dr. Hyman: So impaired sleep from anything? Dr. Bredesen: Absolutely, impaired sleep from anything. Dr. Hyman: Okay, so we got that. Now, what about the things you can do to fix it? Dr. Bredesen: So we go through, we actually gather right now over 100 different pieces of information from the lab values from historical issues, all. And then, actually we have an algorithm that we’ve developed with a group in Silicon Valley where we can look and say, “Okay, this person has 23% type 1 and 35% type 2, whatever. And then, it generates also an initial report on how do you attack all these things. So there are lots of different pieces and very much a functional medicine approach. So things that tend to be at the top of the list, we want to establish insulin sensitivity. Virtually every single person I see has imperfect insulin sensitivity. Many of them will have-- Dr. Hyman: Some type of prediabetes. What I call diabesity. Which, I’ve written a lot of books on, right? Dr. Bredesen: Yes. Of course. And this is something you’ve been talking about for years. And we see people with fasting insulins of 32 or 25 or 15. Dr. Hyman: Oh, my God! And normal is less than five. Dr. Bredesen: Yeah, exactly. We tell them “Look, we want to do what Mark Hyman tells us to do, which is getting down 4.5 or below.” Which is what you usually suggest. So we want to get them down. Now, that’s a big one. The second thing we see is people who have high hs-CRPs. And so we want to get them resolved. And we have been using these pro-resolving mediators. Dr. Hyman: That’s a marker of inflammation.


Dr. Bredesen: A marker of inflammation, so very common. And they’ve often had a chronic inflammation, which they haven’t been able to resolve. So we want to look at what’s causing this and help them to resolve that. Dr. Hyman: Covers infections or mold or what they’re eating or-- Dr. Bredesen: What they’re eating? Exactly. Are they eating a lot of trans fats? Are they living a sedentary— Dr. Hyman: And you use certain supplements to help cut it down. Yeah. Dr. Bredesen: Exactly. And then also trying to get to the root cause. And then, the third thing, we see very frequently people with high homocysteine’s, very common. And there is a tremendous literature-- Dr. Hyman: And that’s a sign of a folate deficiency. Dr. Bredesen: Exactly. And it’s also, homocysteine has a really interesting effect on the brain. So one of the things that homocysteine does, it actually changes the post-translational modification. So you literally change the structure of the PP2A phosphatase, which takes the phosphorylation of tau. So as your homocysteine goes up, your phosphorylated tau is present more. Dr. Hyman: And what that is in English, it means when you have high homocysteine, it makes you have more of these tangles that tangles up your brain. Dr. Bredesen: Exactly. You’ve got the biochemistry that’s driving you towards the tangles. And it has multiple other effects, as well, excitotoxic effects, for example. It has a pro-inflammatory endoplasmic reticulum stress. So it has a lot of damaging things. So we want to get your homocysteine down. Dr. Hyman: In English that means this is bad for you. Dr. Bredesen: Bad for you. That’s right. And, in fact, some beautiful studies out of the U.K. showing that literally, you can place how quickly your hippocampus is shriveling on top of your homocysteine over the years. And, in fact, if you treat that and bring it down below 7, it literally flattens out. Beautiful. So we want to get people to bring their homocysteine down. And then another—


Dr. Hyman: And that’s just taking the right vitamins, right? Dr. Bredesen: Exactly. Dr. Hyman: And alcohol will make it go up. Dr. Bredesen: And alcohol. And we want to get people typically on methylfolate, of course. Methyl B-12, typically because there are so many people who are poor methylators. And, of course, P-5-P-- Dr. Hyman: It’s a special type of B vitamins, not just the regular run of the mill kind you get in the grocery store, but like special types that work to get this down. Dr. Bredesen: Absolutely. And then, of course, for the people who don’t get it down far enough, we want to add trimethylglycine. So we usually give them a few months. And then we add the trimethylglycine, if that is needed. And then another common, as you know, is low vitamin D. And I’m always surprised by how many people are walking around with suboptimal vitamin Ds. And again, we probably weren’t made to spend so much time indoors, wrapped up in the garb that we have. We need to get outside and get more sun and all that sort of stuff. Dr. Hyman: Sunblock. Dr. Bredesen: Exactly right. And this, as you know, affects-- Dr. Hyman: So we’re going to have beautiful skin, but be demented if we don’t deal with that. Dr. Bredesen: Exactly right, beautiful skin, but dementia. So these are all things that are important contributors, and then, of course, reductions in estradiol and testosterone. And even estradiol to progesterone ratio is critical for optimal brain function, so all those things. Dr. Hyman: So the good news is you can get rid of the dementigens. The things we talked about. And you can add these things that are going to help you fix the problem. Fix the insulin resistance and the sugar and the starch. Get rid of that. Deal with these inflammatory things that are going on in your body. Take B vitamins, the right B vitamins. Take vitamin D. All these powerful things. Get enough sleep. These are exercises. These are simple things you’re talking about.


Dr. Bredesen: Optimize thyroid function is another one, commonly. Dr. Hyman: Optimize hormones. Optimize sex hormones—testosterone, estrogen, progesterone, these are things that are relatively simple to do. They’re low risk that are low cost that are profoundly beneficial and aren’t really rocket science. But when you put them all together and you take out the bad stuff, you put in the good stuff, like functional medicine says people have amazing recoveries and from an incurable disease. This is really revolutionary. And I know we’re going to do amazing stuff together. There’s a website I know that you have. Dr. Bredesen: MPICognition.com. Dr. Hyman: MPICognition.com, where people can learn about Dale’s work. Stay tuned to that. He’s coming out with an amazing book. We don’t know the title yet. It’s on reversing dementia. It’s on May 2017. And the documentary, which is going to blow this whole field up because nobody really believes that this is true. And I think when they see these stories and these case histories, it’s going to be extraordinary. So you and I know. David Perlmutter knows. There’s a few of us out there pounding the pavement. But this is really the best kept secret out there. And the good news is like you said 45 million Americans out of our 320 million Americans are going to have dementia if they don’t do something about this. And so the good news is you can prevent it. And you can even reverse early stages. So thank you for your work, Dale. Thanks for being part of The Fat Summit! And so grateful to have you be part of this. Dr. Bredesen: Thanks very much, Mark. Thanks for having me on. And thanks for all the great work. Thanks for all the stuff you’ve taught all of us. Appreciate it. Dr. Hyman: Thank you. Thank you.

hi, i’m dr. mark hyman. welcome to the fat summit...

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