Full Transcript for #370 - Dr. David Perlmutter: Brain Defenders, The Cause Of Dementia, The Missing Puzzle Piece, Microglial Cells, Amyloid Plaque Problems, The Brain's Immune System, APOE4 Risk, Metabolism & Cognitive Health, GLP-1 Benefits, Microplastics & Glyphosate, The Future Of Neurological Support, And More!

[SPEAKER_00]: So definitely look out for that. 04:16.020 --> 04:17.962 [SPEAKER_00]: So today's conversation, 04:18.762 --> 04:21.184 [SPEAKER_00]: is a heavy hitter when it comes to topics. 04:21.304 --> 04:38.635 [SPEAKER_00]: It's something that I've done quite a few, I mean, a lot of different episodes on and that is prevention and the role and the cause of and the treatment for neurological diseases and in particular things like cognitive decline and this topic it affects so many people. 04:39.715 --> 04:53.743 [SPEAKER_00]: and I think people are often looking for hope in this topic because it can seem like there's no answer that what we're doing is not working and the past I've had the investigative journalist Charles Pillaron where he would talk about all of the fraud and the Alzheimer's data research. 04:54.303 --> 05:05.189 [SPEAKER_00]: I've had different people on talking about how diet can maybe help it but regardless it can often seem like they're you know that we can do all of this lifestyle stuff but it can we actually 05:08.971 --> 05:14.534 [SPEAKER_00]: Dr. Pomutter brings to the table an incredible thesis in his new book. 05:14.934 --> 05:16.235 [SPEAKER_00]: It's called Brain Defenders. 05:16.315 --> 05:20.417 [SPEAKER_00]: Harness the power of your immune cells to protect your brain for life. 05:20.937 --> 05:22.898 [SPEAKER_00]: And we're going to talk all about it in this episode. 05:22.938 --> 05:26.000 [SPEAKER_00]: But basically, it goes into the role of the immune system in the brain. 05:26.420 --> 05:40.970 [SPEAKER_00]: in particular something called microglia and how they can either be good guys or bad guys like literally switch back and forth or kind of what we'll talk about it and what we can do to affect that and how that actually ultimately affects our long-term brain health. 05:41.450 --> 05:45.413 [SPEAKER_00]: So he talks about you know all the factors so diet in the book what's actually 05:45.513 --> 05:50.499 [SPEAKER_00]: happening in the brain, all of the new and upcoming potential treatments for cognition. 05:51.100 --> 05:54.383 [SPEAKER_00]: So yes, I have so many questions. 05:54.944 --> 05:58.388 [SPEAKER_00]: Thank you, Dr. Promutter, for all of the work that you've done for years and years and years. 05:58.949 --> 06:00.250 [SPEAKER_00]: And thank you so much for being here. 06:00.571 --> 06:01.151 [SPEAKER_01]: Well, thank you. 06:01.171 --> 06:03.154 [SPEAKER_01]: I'm so delighted to be a repeater fender. 06:03.707 --> 06:05.849 [SPEAKER_00]: that you are, I am delighted you are as well. 06:05.889 --> 06:07.631 [SPEAKER_00]: They haven't locked you up yet, so that's good. 06:08.031 --> 06:12.055 [SPEAKER_01]: Yeah, and you said a lot, I think, to tee up what we're going to talk about today. 06:12.175 --> 06:19.903 [SPEAKER_01]: And that is that, let's take a step back and think about all the places we've been in the past 15 years or so. 06:20.003 --> 06:21.464 [SPEAKER_01]: Yes, we've been talking about. 06:22.245 --> 06:45.414 [SPEAKER_01]: the threat that processed carbohydrate posed to the brain lack of exercise, the role of sleep, Yurik acid, you mentioned that book drop acid, and what is so interesting, and I think Yurik and Entry was a bit appropriate saying it's a bit complicated, but we're now recognizing that all of these factors converge, 06:46.294 --> 06:50.477 [SPEAKER_01]: on a final pathway that explains, I'm just going to say it, everything. 06:50.897 --> 06:57.242 [SPEAKER_01]: And that is, what are these various seemingly disparate inputs doing to the brain's immune system? 06:57.722 --> 07:06.568 [SPEAKER_01]: And it turns out that these changes in the brain's immune system, that he said, well, and microglial cells from being supportive to being destructive. 07:06.628 --> 07:12.632 [SPEAKER_01]: This is upstream of everything in the neurodegenerative world, including Alzheimer's and Parkinson's. 07:13.228 --> 07:29.357 [SPEAKER_01]: and any other neurodegenerative condition you could mention, progressive, supernuclear palsy, multi-system atrophy, MS, and even the shift of these immune cells being involved in things like PTSD, major depressive disorder, and even long COVID. 07:29.417 --> 07:32.118 [SPEAKER_01]: So it throws a very, very large net. 07:32.779 --> 07:38.642 [SPEAKER_01]: I will grant you that it is a bit complicated, but we're gonna tease it apart and make it very understandable and approachable. 07:39.382 --> 07:47.690 [SPEAKER_01]: But I think the gold keys here, the take home message, really is that we have the opportunity and the ability 07:48.504 --> 07:55.089 [SPEAKER_01]: to rain in this immune system and keep it on our side and really change the trajectory of our brain's destiny. 07:55.309 --> 08:01.793 [SPEAKER_00]: Okay, I love this so much and I'm glad that you opened with that because that actually was a major question I had that I was gonna open with as well. 08:01.833 --> 08:10.279 [SPEAKER_00]: So same page, which was, I think you use the phrase somewhere in the book like this is and you kind of paraphrase it now, but like that it's the final piece of the puzzle. 08:10.319 --> 08:13.241 [SPEAKER_00]: Like this is the thing that we've been looking for. 08:13.261 --> 08:15.042 [SPEAKER_00]: A huge question I have is, 08:16.770 --> 08:20.112 [SPEAKER_00]: We'll talk about all of the factors that affect what you were just talking about. 08:21.332 --> 08:29.956 [SPEAKER_00]: It's a lot of lifestyle factors that I think are similar things that you've been talking about for years and years. 08:30.016 --> 08:38.699 [SPEAKER_00]: So my question is, even if we know, like, oh, this is the final piece of the puzzle, does it actually change the recommendations? 08:38.739 --> 08:45.042 [SPEAKER_00]: Does a person even need to know about the final piece of the puzzle if the lifestyle recommendations are the same regardless of that knowledge? 08:45.382 --> 08:47.103 [SPEAKER_01]: The answer is yes and

yes. 08:47.484 --> 08:58.412 [SPEAKER_01]: I think, first of all, understanding what it's doing and all the inputs will allow you to recognize not just to do the things, the exercised attention to your sleep, eat right. 08:58.892 --> 09:07.659 [SPEAKER_01]: But when you grasp that it's changing the function of your brain's immune system, and in fact, the immune system throughout your body, it has more traction. 09:07.819 --> 09:08.620 [SPEAKER_01]: And the second thing 09:11.582 --> 09:35.633 [SPEAKER_01]: you don't know all that's going on and the book reveals the leading edge in terms of other things that can now be done to evaluate yourself, to follow what's going on with your body's metabolism and even what the future holds as it relates to even technology that is now being utilized to reprogram these microglial brain immune cells back to being supportive and away from being destructive. 09:35.693 --> 09:35.793 [SPEAKER_01]: So 09:36.493 --> 09:56.922 [SPEAKER_01]: You know, that's new information and for me, it's hugely exciting information that while we know all the things that we can do readily right now are going to work through this pathway, how encouraging it is to know that this is really where neuroscience is now and where the resources are going to be directed. 09:57.602 --> 10:06.973 [SPEAKER_01]: And, you know, as it relates to Alzheimer's away from this idea that Alzheimer's is caused by the accumulation of this beta-amilite protein in the brain. 10:07.593 --> 10:15.622 [SPEAKER_01]: Greatfully, we're moving past that, recognizing that is not the answer, and therefore all of these drugs being developed to get rid of beta-amilite and brain. 10:16.323 --> 10:33.606 [SPEAKER_01]: are really coming up empty-handed as we've just learned from a very global Cochrane analysis of 17 different studies, indicating that while these drugs are significantly dangerous, their efficacy is almost nil or the word used in the Cochrane analysis was trivial. 10:34.286 --> 10:42.048 [SPEAKER_01]: So, you know, the point I'm trying to make is yet, we're going to certainly impact the science that supports the interventions that we make, 10:42.688 --> 10:59.201 [SPEAKER_01]: But also keep in mind that this is where leading research and technology is exploring how to keep the brain to immune system, on track, and supportive so that those microglue cells are brain defenders and not brain destroyers. 11:00.272 --> 11:04.113 [SPEAKER_01]: high tech is great, but we have the tools right now that each and every one of us can implement. 11:04.433 --> 11:18.697 [SPEAKER_00]: And how much not to like start off on a controversial fight, but I'm still I'm so glad you're saying this because it's confusing hearing about all the potential and and hearing how much people are aware that certain drugs are not working and still. 11:19.417 --> 11:22.340 [SPEAKER_00]: feeling like that part is being championed. 11:22.800 --> 11:30.207 [SPEAKER_00]: So like I mentioned that how I interviewed Charles Pillar, who like uncovered all of that fraud and all of the like medications for Alzheimer's. 11:30.247 --> 11:36.653 [SPEAKER_00]: And that was one of the most like most eye-opening slightly disheartening book I've ever read. 11:36.693 --> 11:38.595 [SPEAKER_00]: I was like, wow, I had no idea that's just going on. 11:38.995 --> 11:42.178 [SPEAKER_00]: And so then once I read that I was like, okay, so everybody's on the same page here that 11:43.039 --> 11:44.201 [SPEAKER_00]: you know, we need something different. 11:44.581 --> 11:48.786 [SPEAKER_00]: But then I interviewed and it was an incredible interview and I love a book and I recommend it. 11:48.806 --> 11:50.268 [SPEAKER_00]: But I was actually telling you this on email. 11:50.288 --> 12:00.020 [SPEAKER_00]: I interviewed Dr. Zaldi Tom last week and he was he had the like the memory and brain center at Cedar Sinai, like his book kind of stole spoke favorably about these drugs and kind of 12:00.721 --> 12:03.702 [SPEAKER_00]: was skeptical of some of the other things. 12:03.802 --> 12:05.422 [SPEAKER_00]: And so it's hard to know. 12:05.462 --> 12:11.304 [SPEAKER_00]: And like you mentioned in your book, how you wrote into the land set because they kind of left out. 12:12.204 --> 12:15.705 [SPEAKER_00]: Then they left out like the lifestyle piece or of prevention. 12:15.985 --> 12:17.605 [SPEAKER_00]: They left out something like really major. 12:17.625 --> 12:20.606 [SPEAKER_00]: And they didn't really accept what you guys wrote in. 12:20.646 --> 12:22.907 [SPEAKER_00]: So but you do feel like we are making. 12:23.627 --> 12:28.049 [SPEAKER_00]: forward movement and that this is going to be the focus or more accepted. 12:28.769 --> 12:29.589 [SPEAKER_01]: It's hard to say. 12:29.849 --> 12:39.293 [SPEAKER_01]: I have to admit it's hard to say because there is huge support for drug development and I'm very supportive of that approach. 12:40.161 --> 12:50.065 [SPEAKER_01]: So that should very much, I think, nuance our conversation moving forward that when there is a drug that's demonstrated to be effective and safe, I am 100% all in. 12:50.745 --> 12:59.489 [SPEAKER_01]: This is a devastating condition if we're talking about Alzheimer's, 7.6 million Americans who have nothing to turn to from the world of pharmacy right now. 12:59.589 --> 13:01.590 [SPEAKER_01]: And again, it's not that, 13:02.290 --> 13:23.063 [SPEAKER_01]: I'm your guest on your program today and I'm telling you that we just had the publication of an incredibly large study called a Cochrane Analysis more than 20,000 because 20,342 individuals 17 different studies each of these studies was 18 months long looking at do the drugs were 13:23.403 --> 13:26.408 [SPEAKER_01]: or do they not work and, importantly, how safe are they? 13:26.508 --> 13:38.427 [SPEAKER_01]: And their conclusion was that about one and four people who use these intravenous amoloid targeted drugs have a side effect, which can

be either bleeding into the brain and or swelling of the brain. 13:38.947 --> 13:40.007 [SPEAKER_01]: and or dying. 13:40.567 --> 13:45.208 [SPEAKER_01]: Okay, maybe that's a risk I should take if I have Alzheimer's disease or my father or mother does. 13:45.768 --> 13:46.929 [SPEAKER_01]: How well do they work? 13:47.429 --> 13:47.789 [SPEAKER_01]: They don't. 13:48.209 --> 13:52.090 [SPEAKER_01]: That's what the study concluded that their effectiveness is trivial. 13:52.750 --> 14:01.932 [SPEAKER_01]: So, I am in the camp that would say, let's look at the work of Dr. Rudolph Tansy and Dr. Dean Ornish that was published from the work they did at a 14:03.432 --> 14:07.673 [SPEAKER_01]: 51 individuals enrolled in a trial with existing Alzheimer's disease. 14:08.254 --> 14:25.339 [SPEAKER_01]: 20 weeks, we're going to change your diet, increase your exercise, reduce your stress, and what did they find that in 70% of these individuals, they either stabilize, which no drug has ever done, or they actually improved on their metrics of cognitive function. 14:25.659 --> 14:25.859 [SPEAKER_01]: Now, 14:26.805 --> 14:30.948 [SPEAKER_01]: That's what the published peer-reviewed science is telling us. 14:31.809 --> 14:36.332 [SPEAKER_01]: I'm not anti-drug when you can show me a drug is working in the Alzheimer's patient. 14:36.813 --> 14:45.319 [SPEAKER_01]: I am all in and as you know in the book, we actually approach the potential future for the GLP-1 Agonist drugs, the OZEMP-like drugs. 14:45.619 --> 14:52.825 [SPEAKER_01]: And I came out in the book saying that when these drugs are proven safe and effective, will I be in? 14:53.145 --> 14:55.086 [SPEAKER_01]: I'll be all in, you bet. 14:56.287 --> 15:03.758 [SPEAKER_01]: I'm not sure that was the response to your question you were looking for, but I want to really clarify that I just want to do what's best for the patients and their loved ones. 15:04.359 --> 15:06.122 [SPEAKER_01]: It's a rough, rough road. 15:06.682 --> 15:09.266 [SPEAKER_01]: I've been down that road with my dad dying of Alzheimer's. 15:09.767 --> 15:10.408 [SPEAKER_01]: It's just 15:11.309 --> 15:11.830 [SPEAKER_01]: horrendous. 15:12.390 --> 15:18.815 [SPEAKER_01]: And if there's a way I can move the needle and add tools to the toolbox, I'm in. 15:18.935 --> 15:25.460 [SPEAKER_01]: If those toolboxes are lifestyle adjustments, which we've seen are demonstrated to be effective, am I in? 15:25.680 --> 15:27.842 [SPEAKER_01]: You bet I'll write a book about it as I just did. 15:28.343 --> 15:32.626 [SPEAKER_01]: If it turns out to be drugs, and it's effective and safe, you bet I'm all in. 15:32.666 --> 15:34.107 [SPEAKER_01]: I'll write a book about that too. 15:34.607 --> 15:34.808 [SPEAKER_01]: But 15:35.388 --> 15:38.970 [SPEAKER_01]: We have interesting tools beyond the lifestyle choices these days. 15:39.010 --> 15:40.951 [SPEAKER_01]: We have things like hyperbaric oxygen. 15:41.431 --> 15:45.633 [SPEAKER_01]: We know that there's some incredible pharmaceutical approaches in the future. 15:45.713 --> 15:49.015 [SPEAKER_01]: What will the metformin studies to demonstrate the rapid mice and studies? 15:49.515 --> 15:52.977 [SPEAKER_01]: We know things like ketamine are being demonstrated to increase 15:53.497 --> 16:04.399 [SPEAKER_01]: synaptic connection, which is so important in the Alzheimer's brain, what will dimethyl fumarate, which targets something called the Inter-F2 pathway to reduce inflammation in the brain, do. 16:04.820 --> 16:10.501 [SPEAKER_01]: In the Alzheimer's patient, already approved in multiple sclerosis, things like methylene blue. 16:10.941 --> 16:13.241 [SPEAKER_01]: And as I mentioned, these GLP1 agatist drugs. 16:13.281 --> 16:17.002 [SPEAKER_01]: So, there's a lot of cool things that are being explored right now. 16:17.502 --> 16:19.483 [SPEAKER_01]: There are certainly some exciting things on the 16:20.983 --> 16:32.749 [SPEAKER_01]: Oh my gosh, mitochondrial transplantation and other deep anti-inflammatory approaches, things like trans cranial magnetics, putting people raising the temperature of the brain. 16:32.769 --> 16:36.811 [SPEAKER_01]: We call that thermofabrial therapy and even xenon gas. 16:36.851 --> 16:45.055 [SPEAKER_01]: So, there are a lot of cool things being used, being explored, you know, not ready for prime time, again risk-benefit ratio, being very important. 16:45.783 --> 16:58.712 [SPEAKER_01]: So for now, I write a book about, get your blood sugar into control, increase your exercise, reduce your stress, increase your socialization skills, meet, you know, get together with people, spend time in nature. 16:59.212 --> 17:02.595 [SPEAKER_01]: Let's look at how effective and restorative your sleep is. 17:02.995 --> 17:07.518 [SPEAKER_01]: Let's look at the area breathing, the quality of the air that you're actually breathing. 17:07.538 --> 17:10.140 [SPEAKER_01]: I'm sure you talk to Dr. Austin Pro-Mutter about that. 17:10.680 --> 17:12.401 [SPEAKER_01]: So there's a lot that can be done. 17:15.621 --> 17:31.188 [SPEAKER_01]: focusing on how all of these inputs affect whether your brain's immune system is going to be supportive or destructive because that is what charts your brain's destiny and that is something over which we each have control. 17:31.788 --> 17:44.094 [SPEAKER_01]: So again, in a very real sense what I'm trying to do is is give people the keys to the kingdom here by letting them do the things to reign in their metabolism, to reduce inflammation, to improve mitochondrial function. 17:44.414 --> 18:03.862 [SPEAKER_00]: While you are certainly doing that, yes, I definitely appreciate the nuance and to bring it back to the pathway and speaking of the nuance and everything that you just discussed, you know, it would be, it would be one thing, it's, it's new wants enough that they're, they're these different, you know, pharmaceuticals like, and I appreciate what you're saying about, you know, if they work,

then, you know, you're all for it. 18:04.362 --> 18:06.423 [SPEAKER_00]: It's complicated, it's confusing because. 18:07.263 --> 18:17.447 [SPEAKER_00]: You know, a lot of them, their intention is to remove this amyloid plaque, and yet we know that people can have amyloid plaque and be asymptomatic. 18:17.567 --> 18:30.191 [SPEAKER_00]: Like it doesn't necessarily correlate, and you even say in the book, you know, the amyloid plaque itself is not so much the problem, it's the, it's when it's attacked by these microglion and the inflammation from that. 18:30.311 --> 18:32.092 [SPEAKER_00]: So going into the pathway, 18:32.852 --> 18:33.512 [SPEAKER_00]: So two things here. 18:33.592 --> 18:36.493 [SPEAKER_00]: Number one, was it an overnight epiphany about this? 18:36.533 --> 18:37.674 [SPEAKER_00]: Was it a slow buildup? 18:37.954 --> 18:38.834 [SPEAKER_00]: How did you come to this? 18:39.195 --> 18:39.655 [SPEAKER_00]: Oh gosh. 18:40.235 --> 18:41.295 [SPEAKER_01]: Not an overnight epiphany. 18:41.355 --> 18:47.398 [SPEAKER_01]: I've always, I've always been a bit, I think, skeptical of dogma. 18:47.538 --> 18:52.100 [SPEAKER_01]: I think that, you know, the two things that we have that are unique about being human. 18:52.120 --> 18:54.701 [SPEAKER_01]: We haven't the opposable thumb, which is a handy thing to have. 18:55.101 --> 18:56.461 [SPEAKER_01]: And we have the ability to question. 18:56.601 --> 18:58.042 [SPEAKER_01]: And I, I'm curious. 18:59.062 --> 19:12.387 [SPEAKER_01]: And, you know, I don't out of hand accept the things that, you know, that mainstream science is telling us about one thing or another, because, you know, as time passes, we realize that we may have been off base. 19:12.407 --> 19:13.588 [SPEAKER_01]: So I want to keep an open mind. 19:14.168 --> 19:23.352 [SPEAKER_01]: This idea, the emerald hypothesis that was developed in late 1980s, the original data that validated this as being the cause of Alzheimer's, 19:26.453 --> 19:50.701 [SPEAKER_01]: an extension of the finding of amyloid in people with familial Alzheimer's and the idea that it should immediately out of hand be extended to the typical Alzheimer's patients that we would see in the clinic day in and day out was inappropriate and but unfortunately took hold and really charted the course for this whole out amyloid story from then on. 19:51.262 --> 19:51.742 [SPEAKER_01]: Ultimately, 19:52.637 --> 20:04.945 [SPEAKER_01]: Med students were being told the cause of Alzheimer's is accumulation of beta amoloid and the general public was told well there's this sticky protein called amoloid which is the cause of Alzheimer's disease. 20:05.425 --> 20:06.906 [SPEAKER_01]: Why did that happen? 20:07.226 --> 20:11.789 [SPEAKER_01]: It happened because if that's the cause that is the solution, right? 20:12.310 --> 20:15.612 [SPEAKER_01]: If we got one cause and we can eliminate problem solved. 20:16.412 --> 20:20.415 [SPEAKER_01]: And so billions of dollars were dedicated to the development 20:21.229 --> 20:24.999 [SPEAKER_01]: of drugs that could bind to the beta or activate the immune system. 20:25.449 --> 20:27.230 [SPEAKER_01]: to rid the brain of beta m-loid. 20:27.271 --> 20:34.857 [SPEAKER_01]: These are these monoclonal antibody drugs that facilitate the reduction and removal of beta m-loid from the brain. 20:35.337 --> 20:35.898 [SPEAKER_01]: Do they work? 20:36.298 --> 20:40.281 [SPEAKER_01]: They were incredibly well in terms of getting rid of beta m-loid. 20:40.782 --> 20:41.682 [SPEAKER_01]: You bet they work. 20:42.103 --> 20:48.648 [SPEAKER_01]: Do they have any meaningful effect on the continued decline of cognitive function in the Alzheimer's patient? 20:49.128 --> 20:49.829 [SPEAKER_01]: They do not. 20:50.470 --> 20:52.831 [SPEAKER_01]: So you're treating a biomarker here. 20:53.650 --> 20:54.952 [SPEAKER_01]: the amoloid accumulation. 20:55.432 --> 20:57.715 [SPEAKER_01]: And sure enough, you're doing a heck of a job. 20:58.456 --> 21:03.181 [SPEAKER_01]: But the reality is the Alzheimer's basis are not getting any better with these drugs. 21:03.422 --> 21:13.173 [SPEAKER_01]: And it's not Melanie that you're guessed on your program today is saying this, this is what this Cochrane analysis just revealed to the entire planet. 21:14.298 --> 21:35.613 [SPEAKER_01]: So again, I wish the drug would work because if the drug would work and really have a meaningful effect on Alzheimer's patients, then maybe you would accept the risk because you know face it Alzheimer's is a fatal condition it we don't recognize it, but in elderly Americans is the third leading cause of death. 21:36.433 --> 21:42.497 [SPEAKER_01]: So sometimes when things are that aggressive, like cancer, for example, you take the risk of chemotherapy. 21:42.517 --> 21:46.319 [SPEAKER_01]: That can have, you know, devastating side effects, but you've got nothing else. 21:46.479 --> 21:52.322 [SPEAKER_01]: And if, but yet chemotherapy can cure people, or at least arrest the disease for a time. 21:52.763 --> 21:54.183 [SPEAKER_01]: But these drugs don't do that. 21:54.223 --> 21:56.445 [SPEAKER_01]: So the risk is unacceptable. 21:57.040 --> 22:04.846 [SPEAKER_01]: But again, you know, it is beta-moid, not necessarily a good thing to be in the brain, it isn't, but it is absolutely not the whole story. 22:04.886 --> 22:15.954 [SPEAKER_01]: We've got to go upstream of beta-moid and ask this simple question, what is allowing it to accumulate in the brain and what else is going on that's destroying the brain? 22:16.654 --> 22:21.558 [SPEAKER_01]: That is the activation of the brain's immune system called the microglial cells. 22:23.844 --> 22:24.766 [SPEAKER_00]: Let's dive in. 22:25.066 --> 22:31.536 [SPEAKER_00]: So the microgliel cells, well, first of all, are they, how do they compare to immune cells throughout the rest of the body? 22:32.358 --> 22:38.868 [SPEAKER_00]: Like, is this process that goes away, happening everywhere

in the body and it just manifests as that in the brain? 22:39.068 --> 22:39.548 [SPEAKER_01]: That's right. 22:39.688 --> 22:43.489 [SPEAKER_01]: So these are immune cells in the body just like other immune cells. 22:44.069 --> 22:49.151 [SPEAKER_01]: I would say they're most akin to cells in the rest of the body called macrophages. 22:49.771 --> 22:56.073 [SPEAKER_01]: Interestingly, though, they are quite unique in that they don't come from the bone marrow in during developmental. 22:56.733 --> 22:57.494 [SPEAKER_01]: They're in development. 22:57.654 --> 22:59.715 [SPEAKER_01]: They actually come from what's called the Yoke Sack. 23:00.215 --> 23:18.406 [SPEAKER_01]: So their origin is actually quite different Interestingly though, we've just learned some research past few weeks that there is the migration in midlife in our 50s 60s of peripheral immune cells into the brain as well That may also set the stage for inflammation as well. 23:18.546 --> 23:23.449 [SPEAKER_01]: So but these are I wouldn't say garden variety immune cells but they're behavior 23:24.111 --> 23:29.515 [SPEAKER_01]: and their genetic markers that they express are quite similar to those seen elsewhere in the body. 23:29.755 --> 23:32.857 [SPEAKER_00]: The yolk sack that they come from shows out is out within the brain. 23:33.077 --> 23:34.238 [SPEAKER_00]: Like is it a close system that? 23:34.458 --> 23:36.560 [SPEAKER_01]: No, the yolk sack is outside of the brain. 23:36.580 --> 23:40.702 [SPEAKER_01]: The yolk sack is what originally provides nutrition for the developing embryo. 23:41.023 --> 23:43.664 [SPEAKER_00]: Okay, that's down there, that's why I thought, okay. 23:43.724 --> 23:46.707 [SPEAKER_00]: So they make their way up, they make their way up to the brain. 23:47.167 --> 23:48.067 [SPEAKER_00]: How are things going awry? 23:48.087 --> 23:50.189 [SPEAKER_00]: And what is the root, the root cause? 23:50.229 --> 23:51.630 [SPEAKER_00]: If it's not the beta amoloid. 23:51.898 --> 24:17.970 [SPEAKER_01]: Well, the root cause, and I think that, you know, this is where the science is, as you and I have this conversation, there are changes in these microglial cells that rather than existing and what is called their M2 supportive configuration, what I call brain defenders, where they are nurturing the neuron, they are nurturing the synapses, they're keeping the blood brain barrier working effectively, that they can shift and we'll talk about what causes that shift. 24:18.422 --> 24:29.431 [SPEAKER_01]: to being what's called M1 configuration that actually destroys synapses, threatens the neurons and destabilizes the blood-brain barrier, all of those things are bad. 24:29.991 --> 24:42.902 [SPEAKER_01]: The fact that these immune cells are gobbling up our synapses is very relevant as it relates to Alzheimer's, because Alzheimer's is really a disease characterized by the loss of connectivity. 24:43.722 --> 24:48.947 [SPEAKER_01]: loss of connectivity of one neuron to the next neuron, which happens at the level of the synapse. 24:49.527 --> 24:52.630 [SPEAKER_01]: So at a microscopic level, that's what's going on. 24:52.790 --> 24:59.755 [SPEAKER_01]: At a macroscopic level, people become disconnected as well with themselves, with their environments, with people around them. 25:00.376 --> 25:02.277 [SPEAKER_01]: So it's very much a disconnection. 25:03.137 --> 25:12.399 [SPEAKER_01]: And one would ask, well, what would cause those microglocels to go off-kilter and start destroying our synapses? 25:13.059 --> 25:16.480 [SPEAKER_01]: And many things can help nudge them along to doing that. 25:17.060 --> 25:22.882 [SPEAKER_01]: Unfortunately, one of the biggest influences to polarize these microglocels is age. 25:23.682 --> 25:35.848 [SPEAKER_01]: As we age, we develop more and more of the threatening M1 microglue cells, and it very much explains why risk for these and other neurodegem conditions increases as we age. 25:36.108 --> 25:41.130 [SPEAKER_01]: In fact, the number one risk factor for developing Alzheimer's is age. 25:41.530 --> 25:45.292 [SPEAKER_01]: That is something that should be re-evaluated and restated. 25:45.892 --> 26:04.583 [SPEAKER_01]: Because the diagnosis happens when we begin to fail on various cognitive tests, our memory is failing, we're walking into rooms not knowing why, forgetting people's names, not remembering how to do executive functions like dress ourselves and all of that. 26:05.044 --> 26:08.206 [SPEAKER_01]: That's well along in the time course of this disease. 26:09.323 --> 26:13.265 [SPEAKER_01]: What shifts the microglial cells is very, very important. 26:13.745 --> 26:21.228 [SPEAKER_01]: What shifts the microglial cells, and that's the underlying event in Alzheimer's, are metabolic changes. 26:21.548 --> 26:25.850 [SPEAKER_01]: Changes in metabolism of the microglial cell. 26:25.990 --> 26:28.591 [SPEAKER_01]: In other words, how it uses energy. 26:29.111 --> 26:37.595 [SPEAKER_01]: Now, the good, supportive brain defending microglial cell, primarily depends upon mitochondrial function, 26:38.117 --> 26:41.099 [SPEAKER_01]: to make the currency of energy which is ATP. 26:41.500 --> 26:55.631 [SPEAKER_01]: The shifted microgliel cell to the M1 destructive configuration is a cell whose metabolism has changed to a different form of energy production, far less efficient called glycolysis. 26:56.652 --> 26:59.074 [SPEAKER_01]: Here's the take home message for your listeners. 27:00.071 --> 27:12.429 [SPEAKER_01]: The change in the metabolism of the microglial cell from being supportive, to being destructive, mirrors the change in metabolism that happens to our bodies. 27:13.110 --> 27:14.733 [SPEAKER_01]: Well, I understand that, great. 27:15.113 --> 27:30.722 [SPEAKER_01]: But that's actually incredibly empowering because it means that if we are careful about our body metabolism, we have a long, a great approach to keeping our microglia on our side, to keeping our microglia

supportive and not shifting to being the evil twin. 27:31.542 --> 27:51.365 [SPEAKER_01]: That's why everything we can do to keep our metabolism on track, keeping our weight where it needs to be, our blood sugar, our insulin functionality, our blood pressure, our blood lipids, our bodyweight, through looking at our diets, our exercise programs, the length and quality of our sleep, reducing risk of head trauma by wearing a helmet. 27:51.845 --> 28:01.607 [SPEAKER_01]: interacting with other people, social interactions, spending time in nature, avoiding breathing air that is higher in particular matter like these PM2.5s. 28:02.387 --> 28:12.730 [SPEAKER_01]: All of these things threaten metabolism and as such threaten to polarize from being supportive, to being destructive are microglial cells. 28:13.130 --> 28:19.391 [SPEAKER_01]: I think that's the underpinning that you're looking for because it really ties it, puts a loop on 28:22.092 --> 28:38.628 [SPEAKER_01]: Why, for such a long time, we've understood these relationships, for example, between type 2 diabetes, tripling an individual's risk, or more at a population level, being associated with a threefold increase risk for developing Alzheimer's disease. 28:38.748 --> 28:46.295 [SPEAKER_01]: I mean, inflammatory chemicals in the body shift the microgliel cells from being friend to being foe. 28:46.875 --> 28:54.886 [SPEAKER_01]: And, you know, when we think back about the research that was carried out, oh, back in 2017, you know, I used this research in my lectures. 28:55.406 --> 29:01.655 [SPEAKER_01]: And this is research that published in the journal Neurology, that took a group of people, and 29:02.843 --> 29:05.665 [SPEAKER_01]: follow them for 24 years. 29:05.805 --> 29:11.410 [SPEAKER_01]: What they did at the very beginning of the study was they measured inflammatory markers in the blood. 29:12.190 --> 29:20.937 [SPEAKER_01]: Twenty-four years later, they did scans to look at how big is their brain and what is your memory doing and then made a comparison. 29:21.517 --> 29:25.300 [SPEAKER_01]: What is the relationship between having inflammation in your bloodstream? 29:26.301 --> 29:32.865 [SPEAKER_01]: a quarter century ago and risked today to having compromised memory and a smaller brain, what did they find? 29:32.985 --> 29:34.626 [SPEAKER_01]: A dramatic relationship. 29:34.926 --> 29:41.130 [SPEAKER_01]: The point there is that, okay, we knew that inflammation the study demonstrated is bad for the brain. 29:41.450 --> 29:42.071 [SPEAKER_01]: But why? 29:42.971 --> 29:43.872 [SPEAKER_01]: Why does it happen? 29:43.952 --> 29:46.173 [SPEAKER_01]: That's the uninterquestion until recently. 29:46.873 --> 29:50.356 [SPEAKER_01]: Inflammation in the body makes its way to the brain. 29:51.257 --> 29:56.327 [SPEAKER_01]: and it will shift the microglial cells away from being friendly to being non-supported. 29:57.089 --> 30:01.538 [SPEAKER_01]: So, I mean this is important research for another very important reason and that is 30:03.182 --> 30:10.428 [SPEAKER_01]: starts to make us think about the fact that, you know, Alzheimer's isn't a problem that begins when your memory starts to become compromised. 30:10.828 --> 30:12.569 [SPEAKER_01]: You don't have a heart attack. 30:12.990 --> 30:14.851 [SPEAKER_01]: You're not attacked out of the blue. 30:15.412 --> 30:21.816 [SPEAKER_01]: You know, that coronary artery stenosis has been going on an awful long time until that heart attack happens. 30:21.836 --> 30:24.459 [SPEAKER_01]: It's not like you're walking and you turn a corner bang. 30:24.479 --> 30:25.279 [SPEAKER_01]: Somebody attacks you. 30:25.319 --> 30:26.180 [SPEAKER_01]: You have a heart attack. 30:26.600 --> 30:28.902 [SPEAKER_01]: No, you're building up to Alzheimer's. 30:32.945 --> 30:47.814 [SPEAKER_01]: That's what is so fundamental that we've got to really target the 30 and 40 worlds in terms of their metabolism and say you know with an elevated waste to hip ratio, bigger belly than you should have in comparison to your hips. 30:48.394 --> 30:53.538 [SPEAKER_01]: That's a risk for becoming an Alzheimer's patient 10, 20, 30 years from now. 30:54.038 --> 30:56.039 [SPEAKER_01]: If your blood sugar is elevated, if you're on your 30:57.738 --> 31:00.242 [SPEAKER_01]: You need to turn around and go down a different road. 31:00.603 --> 31:00.943 [SPEAKER_01]: Why? 31:01.104 --> 31:10.219 [SPEAKER_01]: Because as mentioned, having Type II diabetes is associated with a three-fold increased risk for becoming an Alzheimer's patient. 31:10.890 --> 31:18.594 [SPEAKER_01]: a study way back in 2008, looked at what's called central obesity, having more belly fat. 31:19.115 --> 31:33.082 [SPEAKER_01]: And what they found was three decades later, 30 years later, those who had the largest amount of belly fat, 30 years ago had increased risk for developing dementia of three fold. 31:33.523 --> 31:33.903 [SPEAKER_01]: And again, 31:34.948 --> 31:36.949 [SPEAKER_01]: Now you're demented, what do you do? 31:37.289 --> 31:42.671 [SPEAKER_01]: And the pharmacy world has nothing to offer you as we have this conversation right now. 31:43.011 --> 31:49.914 [SPEAKER_01]: And again, your guess is saying, I'm hoping that happens because not everybody's gonna do the right things right now. 31:50.234 --> 31:56.317 [SPEAKER_01]: It's all about raining in your metabolism and start now when you're still young and cognitively intact. 31:56.778 --> 32:18.653 [SPEAKER_00]: A lot of questions about the microglia, but before that, so because you just mentioned two studies where a significant amount of time later, the inflammatory factor or the weight gain still correlated to issues years and years later, were all of the people still in that state from like similar inflammation from 24 years prior or similar weight from 30 years prior. 32:18.873 --> 32:19.654 [SPEAKER_01]: They didn't look at that. 32:20.034 --> 32:24.797 [SPEAKER_01]: What they looked

at was a unique measurement, just like in the other study that I quoted, 32:26.515 --> 32:30.279 [SPEAKER_01]: the inflammatory markers and then the people were followed years later. 32:30.299 --> 32:40.108 [SPEAKER_01]: So, you know, but I think what you're getting at is, okay, you had increased waist to hip ratio, yet a bigger belly when you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you were, you 32:40.475 --> 32:44.478 [SPEAKER_01]: 30 or 40 years old, is there benefits to losing that billy? 32:45.259 --> 32:46.179 [SPEAKER_01]: You bet there is. 32:46.600 --> 32:49.782 [SPEAKER_01]: That's what these programs that you're hearing about are all about. 32:50.182 --> 32:52.905 [SPEAKER_01]: Study came out in the journal American Medical Association. 32:52.925 --> 32:55.587 [SPEAKER_01]: I think it was last year called The Pointer Study. 32:55.607 --> 33:03.192 [SPEAKER_01]: And this is a study that it was an interventional trial on people who are, maybe their average age was 69 and a half years. 33:03.833 --> 33:06.995 [SPEAKER_01]: And these people had metabolic issues, 33:10.085 --> 33:18.931 [SPEAKER_01]: And in a two-year period of time, people at this age should be expected to decline cognitively. 33:19.411 --> 33:22.073 [SPEAKER_01]: That's just what happens, that's well-documented. 33:22.153 --> 33:25.395 [SPEAKER_01]: But the pointer trial did an intervention. 33:25.435 --> 33:32.799 [SPEAKER_01]: And what the intervention was was to change their diets, to increase their exercise, reduce stress, and they did brain games. 33:33.360 --> 33:36.662 [SPEAKER_01]: They did an at-home kind of online training 33:37.160 --> 33:37.700 [SPEAKER_01]: experience. 33:38.580 --> 33:39.801 [SPEAKER_01]: They divided the group in half. 33:40.001 --> 33:43.241 [SPEAKER_01]: And again, we're talking about 10,000 people in each group. 33:43.982 --> 33:45.662 [SPEAKER_01]: One group had handholding. 33:45.682 --> 33:57.625 [SPEAKER_01]: In other words, during the two year period, they had about 36 or 38 different interventions, not meetings rather, with coaches to see how you're doing, how you're eating, how how's it going. 33:58.005 --> 33:59.445 [SPEAKER_01]: The other group had three a year. 33:59.745 --> 34:02.246 [SPEAKER_01]: So they were how wouldn't say neglected, but they were given the program. 34:02.266 --> 34:04.527 [SPEAKER_01]: They said, dear best, and we'll see how you do. 34:04.547 --> 34:05.387 [SPEAKER_01]: We'll check back in a 34:06.667 --> 34:18.355 [SPEAKER_01]: So, he findings were really interesting because the group that had the aggressive handholding had a dramatic, not stabilization, a dramatic improvement in their cognitive function. 34:19.036 --> 34:24.039 [SPEAKER_01]: And these were people who were overweight getting

back to your question, sedentary poor diets. 34:24.400 --> 34:27.822 [SPEAKER_01]: But here's the part of the pointer trial that I'm taken by. 34:28.543 --> 34:32.786 [SPEAKER_01]: Even the group that had only six interventions or interactions, better words. 34:33.366 --> 34:56.079 [SPEAKER_01]: with the course directors, even these guys who didn't really get the hand holding had dramatic improvement, not quite to the extent that the people had more interface with the course directors, but even these people are basically given the program they said, do your best, we'll check back a couple times a year, do your best, cognitive testing of these individuals after the two years was remarkable. 34:56.891 --> 35:17.732 [SPEAKER_01]: What does it tell you that this is a huge missed opportunity that the world needs to know about one other nuance of this interventional trial about a quarter of the people carried the so-called APOE for genetic marker, putting them at even higher risk for cognitive decline and actually, 35:18.332 --> 35:20.074 [SPEAKER_01]: full-blown Alzheimer's disease. 35:20.454 --> 35:27.701 [SPEAKER_01]: So these days people get their genome sequence, they find out their apioe for positive, they think, oh my gosh, I'm doomed. 35:28.481 --> 35:29.002 [SPEAKER_01]: Not at all. 35:29.602 --> 35:36.569 [SPEAKER_01]: This is the power of lifestyle modification in terms of preserving the brain and reversing decline. 35:37.442 --> 35:39.443 [SPEAKER_00]: going back to the microglia. 35:39.543 --> 35:46.948 [SPEAKER_00]: So I was really fascinated that M1 are the, the quote, you know, the inflammatory bad guys and the M2 are the quote, good guys. 35:47.388 --> 35:48.348 [SPEAKER_00]: So a few different questions here. 35:48.589 --> 35:52.731 [SPEAKER_00]: One is, I don't know if they discovered those at the same time. 35:52.791 --> 35:55.092 [SPEAKER_00]: I'm assuming that M1 was discovered first. 35:55.553 --> 35:58.895 [SPEAKER_00]: I'm assuming they found the pruning, gobbling up version first. 35:59.635 --> 36:01.857 [SPEAKER_00]: Or I could be wrong and they could have gone out of order naming them. 36:01.917 --> 36:17.470 [SPEAKER_00]: But my question is the gobbling that they do, the pruning that they do, is it both, is it like pruning, is it good pruning, like when you're growing and developing your brain and getting rid of cells that you don't need, is it getting rid of infections? 36:17.590 --> 36:19.211 [SPEAKER_00]: Is it like what starts it? 36:19.432 --> 36:26.377 [SPEAKER_00]: And does every microglia cell become at some point in M1 or an M2 or some only in M2 or some only in M1? 36:27.138 --> 36:28.219 [SPEAKER_00]: how fast did they turn over? 36:28.659 --> 36:31.480 [SPEAKER_00]: Like what is the day in the life of a microclient cell? 36:31.700 --> 36:37.423 [SPEAKER_01]: Well, first of all, this was actually discovered not necessarily on the microgliel cells themselves. 36:37.443 --> 36:40.364 [SPEAKER_01]: So it was actually discovered in peripheral cells. 36:40.424 --> 36:52.490 [SPEAKER_01]: So this happened around 2000 when we discovered that there are receptors on immune cells in the body called trem receptors. 36:54.151 --> 37:18.979 [SPEAKER_01]: triggering receptor expressed on myelocytes, and it was recognized that these receptors when they were stimulated would either cause that myelocytes to either be in one configuration or the other, and subsequently it was learned, these receptors, these trim, triggering receptors expressed on myelocytes were actually triggering receptors expressed on microglial cells. 37:23.581 --> 37:42.302 [SPEAKER_01]: discovered to be part of the way that the microleal cells were able to either remain in tram two or M2, tram two simulates M2, easy to remember, I have it in the book actually, or when the tram one receptor is stimulated, that tends to morph it to being the evil twin. 37:42.877 --> 37:49.822 [SPEAKER_01]: So the answer question was first discovered peripherally, then found in the brains, immune cells as well, the microglia. 37:50.563 --> 37:56.287 [SPEAKER_01]: And it was a quite a bit later until we recognized that this was involved in the brain. 37:56.307 --> 37:59.129 [SPEAKER_01]: That really occurred around 2012, 2013. 37:59.209 --> 38:04.433 [SPEAKER_01]: As I was actually writing brain brain, we began to see that these variants 38:05.722 --> 38:23.729 [SPEAKER_01]: I hadn't break this down a little bit, that carrying genetic variants of the Trump to receptor, that would tend to keep these microgliel cell supportive, that people who had genetic variants, that would affect that receptor, had an increased risk of Alzheimer's. 38:24.289 --> 38:25.730 [SPEAKER_01]: Interesting, so that really, 38:26.750 --> 38:37.115 [SPEAKER_01]: Now we see that a genetic variant that affects the polarization of these microglial cells, friend or foe, supportive or destructive. 38:37.736 --> 38:48.161 [SPEAKER_01]: If you carry a genetic variant of the receptor that's playing a role in determining good or bad microglia, you had as much as a threefold increase risk for Alzheimer's disease. 38:48.941 --> 38:50.302 [SPEAKER_01]: So, that's exciting. 38:50.382 --> 38:53.963 [SPEAKER_01]: So, you know, one would wonder, you know, why didn't we write about this? 38:54.023 --> 38:55.244 [SPEAKER_01]: Why wasn't it in grain-brain? 38:55.264 --> 38:56.545 [SPEAKER_01]: Why wasn't I lecturing about it? 38:57.125 --> 39:00.346 [SPEAKER_01]: We didn't know this until 2012, 2013. 39:01.007 --> 39:03.828 [SPEAKER_01]: So, you know, this is new information. 39:04.668 --> 39:06.609 [SPEAKER_01]: It ties up a lot of loose ends. 39:06.669 --> 39:07.530 [SPEAKER_01]: That's for sure, because 39:08.510 --> 39:17.435 [SPEAKER_01]: Beyond the trim receptors on the microglial cells, we would ask, well, what other things might that microglial cell bind on its membrane? 39:17.956 --> 39:25.580 [SPEAKER_01]: That could polarize it away from being

supportive and pave the way for destruction or synapses and loss of neurons and all of that. 39:26.161 --> 39:30.883 [SPEAKER_01]: What stimulates that microglial cell away from being a good guy? 39:31.424 --> 39:33.265 [SPEAKER_01]: And it turns out there are a lot of things. 39:37.475 --> 40:05.798 [SPEAKER_01]: Combined it to the surface of the microglousel and immediately shifted away from being supportive and that inflammation can come from anywhere in the body it can come from the gut inflammatory chemicals made from for example a leaky gut because the microbiome is not in good shape not supporting that barrier function of the gut causing increased inflammation in the body that leads to changing of the microglousels from being friend to being full. 40:06.662 --> 40:20.640 [SPEAKER_01]: Well, this leads back to an earlier conversation that we had, showing that when you look at these inflammatory chemicals in people decades earlier that it predicts who's going to have cognitive decline. 40:21.370 --> 40:40.075 [SPEAKER_01]: So, again, this was, you know, 24 years later, if you had inflammatory markers in your bloodstream, detected, this was a study of 1,600 people, that it predicts having problems with your memory and a smaller brain, a quarter century later. 40:40.916 --> 40:41.996 [SPEAKER_01]: Now we understand why. 40:42.016 --> 40:47.957 [SPEAKER_01]: Because these inflammatory chemicals change the microgliel cells exactly, 40:50.757 --> 40:58.602 [SPEAKER_01]: Targeting them, shifting them away from being supportive of them to brain defenders, for being destructive M1, brain destroyers. 40:59.102 --> 41:12.571 [SPEAKER_01]: And let me take this a little bit further because I have had coffee today and you can tell, let me take a little bit further because we now have the ability to image on brain scans, 41:13.203 --> 41:15.406 [SPEAKER_01]: what the microglial cells are doing. 41:15.606 --> 41:16.887 [SPEAKER_01]: And I talk about it in the book. 41:17.488 --> 41:20.532 [SPEAKER_01]: There's a type of pet scan called a TSPO scan. 41:21.573 --> 41:31.776 [SPEAKER_01]: And this TSPO is a protein seen in the M1 destructive microglue cell and not represented on the cell service of the supportive microglue cell. 41:31.816 --> 41:47.681 [SPEAKER_01]: We can image it now because there are tagged binders to the protein that will bind the protein and then it will light up on a PET scan showing that this is a brain that's got a lot of activation of the microglue cells to M1 being destructive. 41:52.042 --> 42:01.011 [SPEAKER_01]: where and what clinical situations are these TSPO scans that show the microglial activation, where are these scans positive? 42:01.897 --> 42:12.526 [SPEAKER_01]: Yep, Alzheimer's, Parkinson's, multiple sclerosis, PSP, multi-system atrophy, major depression, long COVID, post-traumatic stress disorder. 42:13.587 --> 42:21.293 [SPEAKER_01]: I mean, these are images showing that what's going on in these brains is activation

on the microgliel cell. 42:21.593 --> 42:26.978 [SPEAKER_01]: We don't see that in the cognitively intact individual without one of these issues. 42:27.912 --> 42:33.254 [SPEAKER_01]: So, you know, if that for me and I talk about it a lot of the book is pretty compelling. 42:33.694 --> 42:36.356 [SPEAKER_01]: Now, you know, this isn't a kind of scan you can go get. 42:36.516 --> 42:51.702 [SPEAKER_01]: It's purely a research tool, but it's sure, and it sure tells us an awful lot about what's really going on across a wide spectrum of neurological issues that is basically making a good brain go bad. 42:53.917 --> 43:03.559 [SPEAKER_00]: Okay, so the TREM receptors on the cells, which is genetic, how much is expressed there originally? 43:03.739 --> 43:05.239 [SPEAKER_01]: Let me work with that for just a second. 43:05.980 --> 43:21.323 [SPEAKER_01]: We talked about the genetics of the trim receptor, that genetic variants of the trim two receptor are associated with increased risk of Alzheimer's, because they're not able, because of the receptor being mutated, it doesn't keep that microglueous cell supportive anymore. 43:22.863 --> 43:24.126 [SPEAKER_01]: Here's an interesting study. 43:24.787 --> 43:31.740 [SPEAKER_01]: It looked at trim one and trim two activity in comparison to two things. 43:32.642 --> 43:33.323 [SPEAKER_01]: Obesity. 43:34.085 --> 43:34.986 [SPEAKER_01]: and diabetes. 43:35.726 --> 43:57.220 [SPEAKER_01]: And what it demonstrated was higher-trem 1 activation, lower-trem 2 activation in both of these, and it was much worse if you had both diabetes and uR obese, meaning much more likelihood of shifting your microglues cells to being destructive, because trem 1 is overactive now, and trem 2 is underactive. 43:58.393 --> 44:14.639 [SPEAKER_01]: Yeah, there are genetic variants, but lifestyle, because it affects metabolism, our risk for diabetes and obesity, has a huge role to play in the shift or not of our microglue of cells through these trim receptors. 44:14.999 --> 44:27.144 [SPEAKER_00]: Okay, wow, are some people just kind of really set up for success where they just don't, like they're for whatever reason they're microglue of cells do not easily switch over to M1, even when faced with things. 44:27.484 --> 44:28.485 [SPEAKER_01]: That's right, absolutely. 44:28.505 --> 44:34.808 [SPEAKER_01]: I mean, in some individuals, this shift happens earlier in life and can be far more destructive. 44:34.828 --> 44:38.350 [SPEAKER_01]: There are genetic variants that are clearly involved here as I've just covered. 44:38.370 --> 44:43.753 [SPEAKER_01]: I mean, you can have variants of trend one, variants of trend two in research settings. 44:44.253 --> 44:53.238 [SPEAKER_01]: You can tinker with the with laboratory mice and and breed laboratory mice that over express trend two or under express trend two. 44:53.998 --> 45:02.305 [SPEAKER_01]: And if they under express tram two, then their microglial cells will shift and they get brain to

generation at a younger age. 45:02.765 --> 45:05.067 [SPEAKER_01]: That exists obviously in humans. 45:05.127 --> 45:10.251 [SPEAKER_01]: We're all different, but I think let's go back to what I think is an important point. 45:10.791 --> 45:15.795 [SPEAKER_01]: And that is there's a huge influence on the trend receptors based upon 45:16.966 --> 45:19.807 [SPEAKER_01]: metabolic markers like obesity and or diabetes. 45:20.367 --> 45:27.168 [SPEAKER_00]: So when people, so like the api tying this into the apioe 4 gene, is that related to the tremor? 45:27.228 --> 45:29.269 [SPEAKER_00]: Is that related to how much ammoid? 45:29.549 --> 45:30.829 [SPEAKER_01]: It's a fascinating question. 45:30.869 --> 45:33.550 [SPEAKER_01]: So the apioe 4 is not a gene. 45:33.710 --> 45:35.210 [SPEAKER_01]: It's an allele. 45:35.750 --> 45:39.031 [SPEAKER_01]: So it's a variation having the apioe 2, 3, or 4. 45:40.611 --> 45:43.893 [SPEAKER_01]: to as protective and protective of the microly on my dad. 45:44.253 --> 45:50.596 [SPEAKER_01]: Three is about neutral and four really sets microglia up for being much more destructive. 45:51.097 --> 45:52.837 [SPEAKER_01]: Sarah Marsi, M.A.R.Z.I. 45:52.897 --> 45:56.559 [SPEAKER_01]: runs the Marsi lab at Queen's College in London. 45:56.679 --> 45:57.720 [SPEAKER_01]: I had her on my podcast. 45:58.218 --> 46:18.665 [SPEAKER_01]: really in her laboratory research made it very clear what happens in the APOE for allele is in a big part explained by what that is doing to influence the microglial cells and their shift from being supportive, making them more sensitive to influences like inflammatory cytokines and metabolic changes. 46:19.296 --> 46:21.897 [SPEAKER_00]: do people with the APO E4 allele? 46:22.537 --> 46:25.278 [SPEAKER_00]: Are they more resilient against infectious disease and things like that? 46:25.298 --> 46:26.358 [SPEAKER_01]: It's a great question. 46:26.398 --> 46:28.919 [SPEAKER_01]: You probably interviewed Dr. Dale Bredison and he has... 46:29.119 --> 46:30.359 [SPEAKER_01]: I did and actually I want to. 46:31.280 --> 46:32.940 [SPEAKER_01]: Oh, okay, well, you should because that's his... 46:33.620 --> 46:46.084 [SPEAKER_01]: He credits the presence of APO E4 allele in Cubans with the time when our ancestors came down from the trees and started to walk on the prairie 46:49.862 --> 46:53.925 [SPEAKER_01]: and therefore there is some sense that carrying APA4 was protected. 46:53.985 --> 46:56.246 [SPEAKER_01]: It wasn't protected in some way. 46:56.707 --> 46:58.808 [SPEAKER_01]: Why would it persist in humans today? 46:58.968 --> 47:01.990 [SPEAKER_01]: If it didn't offer us some benefit at some point? 47:02.150 --> 47:13.338 [SPEAKER_00]: Yeah, because it sounds like it, I mean, I'm taking a very, very high level, but it sounds like when your microglia are in a state where they're very, very quick to turn on to attack mode, 47:13.879 --> 47:23.571 [SPEAKER_00]: I mean that, that then you get all this of chronic inflammation, but presumably you would think you'd be more protected from something actually, you know, that's a problem, like a disease or. 47:23.792 --> 47:30.280 [SPEAKER_01]: Yeah, I mean for somebody to be present in 25% of, in this case, Americans, there has to be some... 47:31.021 --> 47:31.922 [SPEAKER_01]: protective effect. 47:32.202 --> 47:40.669 [SPEAKER_01]: We know that, as mentioned, that carrying APOE for a little does promote a stronger innate or built-in inflammatory response. 47:41.250 --> 47:49.177 [SPEAKER_01]: And this probably served to be very beneficial in our ancestors with high rates of infection and parasites. 47:49.257 --> 47:53.661 [SPEAKER_01]: And, you know, it may have provided a selective advantage for them to survive. 47:54.321 --> 48:01.951 [SPEAKER_01]: especially as it relates to certain infections, APOE4, may again offer some benefit. 48:01.991 --> 48:07.638 [SPEAKER_01]: We know that it is involved in redistributing things like cholesterol and other lipids. 48:07.898 --> 48:10.081 [SPEAKER_01]: And in the case of 48:10.641 --> 48:24.166 [SPEAKER_01]: food scarcity in our ancestors, where we don't have access to food and particularly fat calories, this may have led to some higher efficiency as it relates to transporting lipids throughout the body. 48:24.887 --> 48:27.988 [SPEAKER_01]: So, you know, finally there is some discussion that 48:28.648 --> 48:32.752 [SPEAKER_01]: APOE for may provide advantages during our development. 48:33.033 --> 48:39.219 [SPEAKER_01]: So, and early adulthood as it, you know, and then later in life, increases our vulnerability to cognitive decline. 48:39.239 --> 48:50.090 [SPEAKER_01]: So, I think most of the discussion on APOE for and the upsides would be around the advantage that having higher levels of an inflammatory response, 48:50.988 --> 48:56.713 [SPEAKER_01]: when we are challenged by an infection, would have been a selective advantage for our ancestors. 48:56.853 --> 48:57.653 [SPEAKER_01]: Not so much now. 48:57.914 --> 49:16.929 [SPEAKER_00]: Yeah, and so if you were to develop a pharmaceutical that would maybe be effective, presumably you would want something that would discourage the microglia from turning from M2 to M1, except when actually needed, so like training them properly. 49:17.249 --> 49:17.910 [SPEAKER_01]: Exactly right. 49:20.184 --> 49:22.185 [SPEAKER_01]: Here's where we get back to metabolism. 49:22.785 --> 49:33.190 [SPEAKER_01]: The shift that characterizes the change between and to supportive to M1 destructive is a metabolic shift of the microgliel cell. 49:33.770 --> 49:37.692 [SPEAKER_01]: It changes in their mitochondrial function. 49:38.112 --> 49:41.373 [SPEAKER_01]: mitochondria are making the energy for these immune cells. 49:42.014 --> 49:44.775 [SPEAKER_01]: When mitochondria function is declining, 49:45.602 --> 49:51.945 [SPEAKER_01]: that characterizes and nudges the shift away from M2 to being M1. 49:52.125 -->

49:57.748 [SPEAKER_01]: This is really kind of a central thesis in what is now being called immuno-metabolism. 49:58.248 --> 50:02.850 [SPEAKER_01]: The relationship between the immune system and the metabolism of the body, 50:03.430 --> 50:05.271 [SPEAKER_01]: and the metabolism of that cell. 50:05.751 --> 50:16.116 [SPEAKER_01]: So, whatever we do that threatens mitochondrial function will help polarize those microglia away from being supportive to being destructive. 50:16.656 --> 50:18.918 [SPEAKER_01]: What do we do that threatens our mitochondria? 50:19.278 --> 50:22.299 [SPEAKER_01]: Well, being sedentary, that's definitely not a good thing. 50:22.739 --> 50:29.983 [SPEAKER_01]: Eating foods that are pro-inflammatory, challenging insulin functionality, exposing ourselves to certain mitochondrial toxins, 50:30.915 --> 50:32.496 [SPEAKER_01]: incredibly common these days. 50:33.077 --> 50:39.841 [SPEAKER_01]: And respectfully, for myself, even as we chronologically age, our mitochondrial function declines. 50:40.401 --> 50:45.565 [SPEAKER_01]: So all of the things that certainly have been presented here on your program over the years, 50:46.107 --> 51:06.870 [SPEAKER_01]: that are important for maintaining and even improving mitochondrial function, play into this whole idea that when we target mitochondrial function, IE metabolism, we are actually targeting those microglial cells to shift their metabolism back to relying on mitochondria and allowing them to return to their supportive configuration. 51:07.125 --> 51:26.909 [SPEAKER_00]: Okay, okay, wow, so just to be super clear, so when the microglia are in the good M2 version, their mitochondria is functioning well when they're in the M2 quote bad version, they're running on glycolysis now, or is it like just a shift in? 51:26.929 --> 51:35.731 [SPEAKER_01]: And that is exactly what happens that glycolysis takes over and to clarify for you listeners, that is a much less efficient way. 51:36.651 --> 51:42.275 [SPEAKER_01]: of creating these ATP molecules that, you know, are the currency of energy in the brain. 51:42.415 --> 51:51.022 [SPEAKER_01]: So we spend a lot of time on packing this in the book about how diet affects mitochondria, how exercise affects mitochondria. 51:51.062 --> 51:53.864 [SPEAKER_01]: You know, we can talk about sonas and cold plunging. 51:54.426 --> 52:15.491 [SPEAKER_01]: and Collin's on Q10 and AD precursors, things like MidoQ and, you know, all of the things people are thinking about, hyperbaric oxygen therapy, fasting, more ketogenic diet, you know, the various things that are very disjuring, you know, influencers are talking about all these things, has been ways of enhancing mitochondrial function. 52:15.631 --> 52:18.132 [SPEAKER_01]: I didn't want to go that route, you know, it's 52:18.946 --> 52:24.716 [SPEAKER_01]: I'm talking about what is, you know, supported by science, why should we be taking creatine? 52:24.776 --> 52:33.329 [SPEAKER_01]: Now, the creatine improves energy, buffering, and supplies gives us the ability to make a reservoir. 52:33.970 --> 52:42.877 [SPEAKER_01]: for phosphorus to become ATP or phosphate to become ATP by bonding by creating what's called phosphocreatine. 52:43.538 --> 52:46.480 [SPEAKER_01]: So am I a proponent of creatine as a supplement? 52:46.540 --> 52:47.201 [SPEAKER_01]: You bet I am. 52:47.221 --> 52:48.462 [SPEAKER_01]: Do I take it every day myself? 52:48.482 --> 52:49.142 [SPEAKER_01]: 100% I do. 52:50.667 --> 53:05.997 [SPEAKER_00]: I just want to be very clear, so I understand that if you, if you're metabolism and the mitochondria are supported, that it's in a good functioning state, and if it's not, then it switches to this M1, however, 53:06.917 --> 53:18.945 [SPEAKER_00]: Also, if it was in the M2 state, and you're still in a good metabolism state, I might a country estate, and then you get exposed to something that requires M1, and the switch happens. 53:19.445 --> 53:23.148 [SPEAKER_00]: Does the metabolism also switch in the cell or can it in one cell? 53:23.428 --> 53:24.249 [SPEAKER_01]: Yes, it does. 53:24.669 --> 53:33.356 [SPEAKER_01]: And so let's talk about a scenario when there's a sudden shift in these microglial cells from being supportive to their M1 configuration. 53:33.756 --> 53:42.663 [SPEAKER_01]: Let's be clear, we need the M1 configuration, because that is what we use to get activated to gobble up bacteria when they're in the brain. 53:43.143 --> 53:50.666 [SPEAKER_01]: to get to a place of trauma immediately, or a stroke, you know, that activates these microglutos cells to do good things. 53:51.066 --> 53:57.089 [SPEAKER_01]: But they got it ultimately when they've done their job, they got to go back to the firehouse and maintain the equipment. 53:57.509 --> 53:59.470 [SPEAKER_01]: You got the analogy, we need them acutely. 53:59.910 --> 54:07.773 [SPEAKER_01]: The idea is not to get rid of all the M1, but it's just persistent activation of the M1 that underlies the brain's degeneration. 54:08.213 --> 54:11.615 [SPEAKER_01]: So, yeah, head trauma is a powerful activator. 54:12.295 --> 54:21.702 [SPEAKER_01]: But what if the microgliel cells are already shifted to M1 or there's a situation that tends to keep them in one in M1? 54:22.182 --> 54:25.065 [SPEAKER_01]: Might that make, for example, head trauma worse? 54:25.585 --> 54:26.946 [SPEAKER_01]: Well, let me give you an example. 54:27.767 --> 54:34.472 [SPEAKER_01]: In diabetics who experienced head trauma, their hospitalized longer and their outcomes are poorer. 54:35.437 --> 54:37.342 [SPEAKER_01]: same level of head trauma. 54:37.382 --> 54:43.097 [SPEAKER_01]: These looking at large data sets where, you know, you could pretty well average out the degree of head trauma by and large. 54:43.493 --> 54:45.414 [SPEAKER_01]: Their outcome is worse, why? 54:45.474 --> 54:53.280 [SPEAKER_01]: Because your microglue cells aren't being kept in M1 because of their metabolic

issue, their elevated blood sugar, and their insulin resistance. 54:53.920 --> 55:07.369 [SPEAKER_01]: So it really be hoves us to get metabolic house in order prior to having head trauma, not that we want to have head trauma, but really prior to being exposed to wildfire smoke, you know, having a bad infection, 55:07.829 --> 55:14.156 [SPEAKER_01]: having a leaky gut, having a urinary tract infection, pneumonia, whatever it may be that increases inflammation in the body. 55:14.636 --> 55:16.878 [SPEAKER_01]: You really want your metabolic house in order. 55:17.018 --> 55:25.387 [SPEAKER_01]: I mean, as if you needed any other reasons to do that, but because that is nurturing your microglis cells to do good things for you. 55:25.725 --> 55:30.548 [SPEAKER_00]: And it also sounds like the effect of the cancer switching took like all of this with the cells. 55:30.848 --> 55:33.210 [SPEAKER_01]: Wow, it sure does. 55:34.150 --> 55:41.715 [SPEAKER_01]: It's very interesting that you say that, because cancer cells, as you just pointed out, are using a different method of producing energy. 55:41.735 --> 55:42.936 [SPEAKER_01]: They're using glycolysis. 55:43.756 --> 55:54.985 [SPEAKER_01]: As such, we can shift the ability of cancer cells to energize themselves by depriving them of available glucose by keeping blood sugar much lower. 55:55.485 --> 56:02.971 [SPEAKER_01]: You know, it's why there are books written about ketogenic diets being a way to act as an adjunct way to augment 56:03.572 --> 56:29.175 [SPEAKER_01]: standardized cancer therapies like chemotherapy, radiation theory, of course, and even consider them for more cutting edge approaches like mRNA type interventions and CAR-T therapy, but using a ketogenic diet, we know that Dr. Walter Longo has really made this very clear to all of us that when cancer cells are deprived of higher levels of glucose, they're more susceptible to the targeting effects of these other interventions. 56:29.495 --> 56:34.059 [SPEAKER_00]: And this, I mean, speaking of Dr. Faltre Longo, he's been on the show a few times and I love him as well. 56:34.079 --> 56:36.220 [SPEAKER_00]: So now I'm thinking about like animal studies. 56:36.280 --> 56:37.141 [SPEAKER_00]: Does this happen? 56:37.261 --> 56:38.282 [SPEAKER_00]: Is this unique to humans? 56:38.322 --> 56:39.983 [SPEAKER_00]: Or does this happen in animals? 56:40.283 --> 56:42.225 [SPEAKER_01]: No, you can demonstrate this in animals. 56:42.285 --> 56:46.768 [SPEAKER_01]: And that's where, you know, that's where this warberg effect I think was first demonstrated. 56:47.068 --> 56:53.493 [SPEAKER_00]: Because you talk about the role of like fructose generation in the brain, because you work with Dr. Rick Johnson right on that. 56:53.794 --> 56:54.094 [SPEAKER_01]: Absolutely. 56:54.134 --> 56:56.856 [SPEAKER_01]: So Dr. Johnson and I wrote a paper actually on this, 56:57.576 --> 57:05.880 [SPEAKER_01]: that the brain produces fructose, it has the ability to activate what is called the poly all pathway, the poly all pathway. 57:06.761 --> 57:14.304 [SPEAKER_01]: In the presence of higher levels of glucose, of blood sugar, will convert some of that blood sugar into fructose. 57:14.324 --> 57:21.168 [SPEAKER_01]: The problem with that is the fructose is then metabolized into youric acid and youric acid is 57:22.108 --> 57:33.016 [SPEAKER_01]: a metabolic threat, youric acid threatens the functionality of insulin via downregulating how nitric oxide works and also ultimately threatens mitochondrial function. 57:33.076 --> 57:37.279 [SPEAKER_01]: So indirectly, then, fructose is not good for our mitochondria. 57:37.659 --> 57:41.862 [SPEAKER_01]: Why might we want to ratchet down our mitochondria? 57:42.022 --> 57:42.583 [SPEAKER_01]: Think about it. 57:42.763 --> 57:47.506 [SPEAKER_01]: Why would we want to not be able to use fuel to create energy? 57:47.686 --> 57:50.669 [SPEAKER_01]: Why would it be good for us not to do that if we're starving? 57:51.389 --> 58:03.774 [SPEAKER_01]: or if we can't find food and we still need to keep the brain powered, we want to throttle back the effectiveness of the mitochondria such that we preserve fuel, preserve glucose to keep the brain powered so that we will survive. 58:04.454 --> 58:10.077 [SPEAKER_00]: The correlation I'm trying to think, because I remember you guys talking about the think it was like the naked mole rat or something. 58:10.357 --> 58:16.919 [SPEAKER_00]: There was some animal that was like really unique with this pathway, so I was just wondering if in that animal, if they present it differently, 58:21.161 --> 58:22.962 [SPEAKER_01]: Well, we, you know, we are that animal. 58:23.222 --> 58:25.582 [SPEAKER_01]: That's what bad can make fructose in the brain. 58:25.682 --> 58:28.643 [SPEAKER_01]: So that was really the thesis of our article. 58:28.723 --> 58:40.867 [SPEAKER_01]: But I think if you look at this, what's called the naked mole rat, this can absolutely shift from glucose to fructose driven glycolysis in both its brain and heart. 58:40.887 --> 58:47.829 [SPEAKER_01]: I mean, the real exciting thing about the naked mole rat is its ability to survive for a long period of time. 58:48.389 --> 58:49.951 [SPEAKER_01]: the absence of water. 58:50.572 --> 58:59.100 [SPEAKER_01]: So the idea though is that it is able to use fructose as an alternative brain fuel when it is oxygen deprived. 58:59.220 --> 59:05.407 [SPEAKER_01]: So that's really the exciting thing if one wants to spend some time on the naked mole rat. 59:06.119 --> 59:14.146 [SPEAKER_00]: Okay, another question, because you mentioned this briefly, I had kind of recently Dr. Ben Ryan on, he has a book called Why Brain's Need Friends. 59:14.807 --> 59:19.511 [SPEAKER_00]: It was basically an entire book about the effects of social relationships on the brain. 59:19.611 --> 59:21.613 [SPEAKER_00]: And completely, completely blew me away. 59:21.653 --> 59:24.856 [SPEAKER_00]: Like I

thought I could, I was like, I'm like, what am I gonna learn? 59:24.896 --> 59:29.220 [SPEAKER_00]: Cause like, I don't understand the social is like, good for the brain, I learned so much. 59:29.760 --> 59:30.961 [SPEAKER_00]: Something like, 59:31.682 --> 59:41.005 [SPEAKER_00]: Because you've mentioned like diet and you know exercise and losing weight, which I think are very tangible things that people can you know mark on a chart. 59:41.085 --> 59:48.927 [SPEAKER_00]: But when it comes to lifestyle like having friends and your level of happiness and what are the effects of that on our microclia? 59:49.147 --> 59:52.147 [SPEAKER_01]: It's a great question because it's often times underrated, right? 59:52.308 --> 59:54.268 [SPEAKER_01]: You know where you're ordering at a good night's sleep. 59:55.348 --> 59:57.069 [SPEAKER_01]: Exercise, what do I do? 59:57.229 --> 59:59.810 [SPEAKER_01]: I'll explain, have a great diet and pretty 01:00:01.668 --> 01:00:25.123 [SPEAKER_01]: the important three legs to the stool and they they obviously are but this social interaction idea I think is really very very important when you look at the epidemiology you see that people who are isolated which is something that happens to people as they age they become more and more socially isolated the spouse dies or their separation whatever happens kids grow up and move away. 01:00:26.065 --> 01:00:32.793 [SPEAKER_01]: And it turns out this is a very direct effect on Alzheimer's risk, IE, a direct effect on the brain. 01:00:32.953 --> 01:00:40.382 [SPEAKER_01]: I mean, this was certainly well-characterized from an observational perspective when Dan Butner studied the blue zones. 01:00:41.123 --> 01:00:44.587 [SPEAKER_01]: And you know, found that here's a group of people in various parts of the world. 01:00:45.148 --> 01:00:46.489 [SPEAKER_01]: that were exceptionally healthy. 01:00:46.749 --> 01:00:54.555 [SPEAKER_01]: And for our discussion, we're somewhat resistant, despite their age, to becoming cognitively impaired, IE developing dementia. 01:00:55.256 --> 01:01:03.542 [SPEAKER_01]: So what is it then mechanistically that we could talk about that relates these social interactions to being good for our brains? 01:01:03.962 --> 01:01:09.726 [SPEAKER_01]: And I'm going to tie that all the way back to something called the microglial cells, the brain's immune cells who knew. 01:01:10.547 --> 01:01:11.948 [SPEAKER_01]: Well, there are a couple of things that play here. 01:01:15.030 --> 01:01:16.851 [SPEAKER_01]: and stress increases cortisol. 01:01:17.652 --> 01:01:32.501 [SPEAKER_01]: Higher levels of cortisol are directly toxic to the brain's memory center cells in the hippocampus, but interestingly, higher levels of cortisol elevate our blood sugar and threaten the microbiome to the extent that ultimately, 01:01:33.141 --> 01:01:35.143 [SPEAKER_01]: inflammatory chemicals are increased. 01:01:35.663 --> 01:01:51.775 [SPEAKER_01]: We discussed earlier how those are

both inroads to activating the microglial cells, having elevated blood sugar and inflammation anywhere in the body, can make its way to the brain, target the microglial cells, and shift them away from being friend to being foe. 01:01:52.395 --> 01:01:57.099 [SPEAKER_01]: So those are powerful mechanisms that are at play, day in and day out. 01:01:57.599 --> 01:02:00.640 [SPEAKER_01]: when people are experiencing social isolation. 01:02:01.060 --> 01:02:10.641 [SPEAKER_01]: Like happened during COVID, a great experiment, with an associated increase in incidence of Alzheimer's disease thereafter, was it a direct effect of the virus? 01:02:11.001 --> 01:02:14.302 [SPEAKER_01]: Perhaps, was it a mitochondrial effect of the virus, perhaps? 01:02:14.802 --> 01:02:18.003 [SPEAKER_01]: Was it because of the social isolation as well? 01:02:18.223 --> 01:02:20.263 [SPEAKER_01]: All things I think have merit should be considered. 01:02:20.863 --> 01:02:26.064 [SPEAKER_01]: But let me give you another mechanism that I really liked to describe and I did put it in the book. 01:02:26.645 --> 01:02:33.647 [SPEAKER_01]: And that is, when we're with people and experiencing other people and loving on other people, 01:02:34.337 --> 01:02:38.461 [SPEAKER_01]: We increase the production in our brains of oxytocin. 01:02:38.881 --> 01:02:48.029 [SPEAKER_01]: The love hormone, oxytocin is important for much more than just milk, let down when women begin to nurse. 01:02:48.850 --> 01:02:59.059 [SPEAKER_01]: Oxytocin is related to our emotional state and allows us to feel the things that happen when we're feeling loving towards other people. 01:02:59.980 --> 01:03:00.481 [SPEAKER_01]: Guess what? 01:03:01.515 --> 01:03:12.947 [SPEAKER_01]: Oxytocin receptors on the M2 microglia, like the Trem2 receptors, keep when stimulated, keep that microglial cell in its M2 configuration. 01:03:13.748 --> 01:03:20.354 [SPEAKER_01]: And so go out and hug somebody, but there's merit to connecting to people virtually as well. 01:03:21.002 --> 01:03:30.769 [SPEAKER_01]: And, you know, if being living at your children's home isn't an option for whatever reason, staying in touch, you know, face time, whatever it may be, does good things for you. 01:03:30.789 --> 01:03:36.333 [SPEAKER_01]: You look at their faces, look into the face of a dog, have a pet, it does the same thing. 01:03:38.600 --> 01:03:44.441 [SPEAKER_00]: So I would actually use this as to play Devil's Advocate to, well, maybe not Devil's Advocate. 01:03:44.941 --> 01:03:47.542 [SPEAKER_00]: So you talk about the mind diet in the book. 01:03:47.902 --> 01:03:53.883 [SPEAKER_00]: I've had the researchers, they recently released a book called The Official Mind Diet, or a few years ago. 01:03:53.923 --> 01:04:01.965 [SPEAKER_00]: So I had them on for that, and that's the most technically the most studied diet to prevent or help with cognitive decline. 01:04:02.865 --> 01:04:10.972 [SPEAKER_00]: And one of the things on that diet,

you get bonus points for drinking wine, which I'm a big red wine fan over here. 01:04:11.893 --> 01:04:14.075 [SPEAKER_00]: I would propose because I know when people say, 01:04:15.192 --> 01:04:26.304 [SPEAKER_00]: And you talk in the book about, you know, the French paradox and everything and, you know, is it about the polyphenols and like if it's the polyphenols, you could get those from, you know, somewhere else without the alcohol. 01:04:27.125 --> 01:04:35.774 [SPEAKER_00]: I feel like they're assuming you're not getting, like, assuming you're not binge drinking and you're not drinking for, like, to self medicate yourself. 01:04:36.555 --> 01:04:47.380 [SPEAKER_00]: I think the social aspect might be a factor in the health benefits that people experience with wine, because of the reasons that you just said, possibly. 01:04:47.540 --> 01:04:49.281 [SPEAKER_01]: I hear you, and it's funny. 01:04:49.301 --> 01:04:58.045 [SPEAKER_01]: I remember during COVID that Austin, Pralmutter, and I did an interview to each other for social media to answer this question. 01:04:58.565 --> 01:05:00.186 [SPEAKER_01]: And he brought that up. 01:05:00.206 --> 01:05:03.847 [SPEAKER_01]: There's this social relaxation, interaction thing that happens when 01:05:05.445 --> 01:05:06.686 [SPEAKER_01]: and is that an offset? 01:05:07.027 --> 01:05:14.374 [SPEAKER_01]: And that and the polyphenol story, of course, has been, have been recognized as, you know, having some positive effects. 01:05:15.034 --> 01:05:23.963 [SPEAKER_01]: I think that there's continuing to be a shift to the idea that any alcohol is not good for the brain. 01:05:24.543 --> 01:05:45.032 [SPEAKER_01]: In there's been this discussion of the so-called U-shaped curve where Alzheimer's risk at the very lowest end of Alzheimer's of a rather alcohol consumption is at a certain level that after one glass of wine for women per day and two glass wine for men per day, then the lowest risk and then more than that the curve goes right back up so it's U-shaped. 01:05:45.992 --> 01:05:52.594 [SPEAKER_01]: I'm of the mind that no pun intended, that less is best, and I will be the first of it. 01:05:52.694 --> 01:06:03.117 [SPEAKER_01]: I've enjoyed my wine over the years, being very restrictive, but I've very much enjoyed it, and I might still have a glass of wine from time to time to fully transparent. 01:06:03.797 --> 01:06:09.539 [SPEAKER_01]: But, you know, the idea of a glass of wine at dinner, something that you do every night, because that's what Italians and French people do. 01:06:10.464 --> 01:06:13.927 [SPEAKER_01]: It's great, it's wonderful, but that's not where the science is right now. 01:06:14.047 --> 01:06:21.234 [SPEAKER_01]: So, you know, I recognized that early on in the mind diet, that Martha Claire Morris was a bit of an advocate. 01:06:21.274 --> 01:06:29.101 [SPEAKER_01]: You know, her first paper published in 2015, I think, made it clear that there was at that time considered to be an

upside. 01:06:29.141 --> 01:06:34.225 [SPEAKER_01]: But I think more recent research would indicate that it's probably not the best choice. 01:06:35.366 --> 01:06:36.767 [SPEAKER_01]: So, I mean, the argument, let's say, 01:06:37.630 --> 01:06:42.647 [SPEAKER_01]: In favor of the polyphenols, get your polyphenols from other sources from olive oil from coffee. 01:06:43.297 --> 01:06:51.364 [SPEAKER_01]: from himaly and tardory buckwheat, whatever the case may be, colorful vegetables, or there are companies that make alcohol free wines. 01:06:51.444 --> 01:06:58.670 [SPEAKER_01]: If you want, you really want to have that glass of wine, trick yourself, and get extremely low alcohol wine, or not. 01:06:58.930 --> 01:07:10.600 [SPEAKER_01]: I mean, if it's the polyphenol part of the story, the number one source of polyphenols on the planet is coffee, but you know, colorful foods, you're going to get your polyphenols, you want more than each sprouted foods, 01:07:11.338 --> 01:07:19.321 [SPEAKER_01]: And as I say, this Himalayan targeted buckwheat that we're hearing about is really one of the richest source of polyphenols that I've ever seen. 01:07:19.341 --> 01:07:26.523 [SPEAKER_00]: I actually just released a coffee line and it was specifically source high CGA antioxidant coffee. 01:07:26.624 --> 01:07:29.044 [SPEAKER_00]: So I'm all about the coffee. 01:07:29.384 --> 01:07:31.265 [SPEAKER_00]: I'm a slow caffeine metabolizer though. 01:07:31.285 --> 01:07:34.866 [SPEAKER_00]: I'm a fat alcohol metabolizer and slow caffeine metabolizer. 01:07:34.926 --> 01:07:37.848 [SPEAKER_00]: So yes, a little bit of coffee and I'm good. 01:07:38.148 --> 01:07:39.128 [SPEAKER_00]: Can you have a lot of coffee? 01:07:39.348 --> 01:07:40.209 [SPEAKER_01]: Yeah, I can. 01:07:40.769 --> 01:07:43.611 [SPEAKER_01]: I really don't because I, you know, it makes me tired. 01:07:44.031 --> 01:07:48.314 [SPEAKER_01]: So I'm very careful, you know, I might have two cups a day and I don't have coffee. 01:07:48.474 --> 01:07:51.216 [SPEAKER_01]: I would love to have a coffee right now, but it's too late and afternoon. 01:07:51.576 --> 01:08:00.962 [SPEAKER_01]: I know it's going to affect my sleep, but, but I think you mentioned very interesting point that there is, you know, the people have different abilities to handle. 01:08:01.422 --> 01:08:13.850 [SPEAKER_01]: The breakdown of caffeine, there's what's called the CYP-102 gene, and variations of that gene can determine whether you can or cannot metabolize that caffeine appropriately, such 01:08:14.584 --> 01:08:16.925 [SPEAKER_01]: you know, caffeine may affect you more than the next person. 01:08:17.325 --> 01:08:18.286 [SPEAKER_01]: So it's good to know that. 01:08:18.566 --> 01:08:20.427 [SPEAKER_00]: Oh yeah, I'm very, very much aware. 01:08:20.507 --> 01:08:25.029 [SPEAKER_00]: I wish I could drink more because it seems like the benefits are, you know, pretty great, especially for the brain. 01:08:25.169 --> 01:08:25.349 [SPEAKER_01]: Yeah. 01:08:25.609 --> 01:08:31.832 [SPEAKER_01]: And to be fair, you know, that gene determines how quickly you're going to break down or metabolize caffeine. 01:08:31.872 --> 01:08:33.472 [SPEAKER_01]: And there, there are other genes as well. 01:08:33.492 --> 01:08:34.653 [SPEAKER_01]: We know that there's the adora 2A. 01:08:35.693 --> 01:08:46.355 [SPEAKER_01]: Gene that doesn't really have a role to play in terms of how you're breaking down the caffeine, but has to do with how sensitive your brain is in terms of responding to caffeine. 01:08:46.455 --> 01:08:50.136 [SPEAKER_01]: So another one that people may know about if they've had their genome sequenced. 01:08:50.896 --> 01:08:54.857 [SPEAKER_00]: So in the in the book you have you have a lot of test options. 01:08:55.477 --> 01:09:01.138 [SPEAKER_00]: Do you recommend should everybody be getting tested or only if they become symptomatic? 01:09:02.158 --> 01:09:03.098 [SPEAKER_00]: What's what's best there? 01:09:03.362 --> 01:09:07.068 [SPEAKER_01]: No, I don't want people to wait till they're symptomatic for anything I recommend the book. 01:09:07.789 --> 01:09:10.533 [SPEAKER_01]: As I said, that's way, way down the continuum. 01:09:10.553 --> 01:09:11.414 [SPEAKER_01]: It's not too late. 01:09:12.155 --> 01:09:17.122 [SPEAKER_01]: But we want to be way, way before that in terms of letting people know where they stand, i.e. 01:09:17.162 --> 01:09:17.563 [SPEAKER_01]: testing 01:09:18.157 --> 01:09:19.778 [SPEAKER_01]: and hear the tools to fix it. 01:09:19.858 --> 01:09:30.701 [SPEAKER_01]: So, earlier on in life, in your 40s, you need to know your fast and glucose, your fast and insulin level, your A1C, your waist to hit measurement. 01:09:31.121 --> 01:09:32.622 [SPEAKER_01]: These are fundamentally important. 01:09:32.642 --> 01:09:33.862 [SPEAKER_01]: You should know your blood pressure. 01:09:34.322 --> 01:09:38.424 [SPEAKER_01]: I mean, how many 40-year-olds know what their blood pressure is or have a check? 01:09:38.932 --> 01:09:41.654 [SPEAKER_01]: Now, are there others that are more brain-specific? 01:09:41.794 --> 01:09:49.719 [SPEAKER_01]: I don't think it's reasonable for a 40-year-old to undergo a, what's called a P, Tao, to 17. 01:09:50.420 --> 01:09:57.165 [SPEAKER_01]: But we now know that there's evidence that this Tao protein in the brain is predicted 01:09:57.970 --> 01:10:13.810 [SPEAKER_01]: years later, 16 years later, a study came out just a couple of months ago, looking at measuring pitao in the brain using PET scan and correlated that with lower levels of vitamin D, 16 years before. 01:10:14.771 --> 01:10:16.493 [SPEAKER_01]: So look at younger people. 01:10:17.542 --> 01:10:20.883 [SPEAKER_01]: Kimmer, their average age, I think it was 39.5, something like that. 01:10:21.623 --> 01:10:32.227 [SPEAKER_01]: And it looked at there, then followed these individuals, and 16 years later did a PET scan that measured the amount of tau in

the brains, which then correlates with Alzheimer's risk. 01:10:32.647 --> 01:10:39.589 [SPEAKER_01]: Those who started off with the lowest level of vitamin D had the highest finding of P-tow in their brains. 01:10:40.029 --> 01:10:45.951 [SPEAKER_01]: P-tow is a predictor of Alzheimer's disease, even in people who are cognitively intact. 01:10:46.151 --> 01:11:04.300 [SPEAKER_00]: So are these, because this is so fascinating to me that these biomarkers, which a lot of which can be changed relatively quickly, if you concentrate, that they last so long, so are people just, and all these studies, these people are just, they're living their same lifestyle the whole time, I guess. 01:11:04.480 --> 01:11:08.962 [SPEAKER_01]: I'm not sure understand the question, you mean that they are evaluated and then, and then what? 01:11:09.250 --> 01:11:23.511 [SPEAKER_00]: So I'm finding it really fascinating because now that's like three different studies you've mentioned where they test a biomarker, two of which can be changed relatively well, like a sit depends what's happening, but one was in the inflammation, one was wait and now one's vitamin D. 01:11:24.552 --> 01:11:27.574 [SPEAKER_00]: And years later, it's predicting things. 01:11:28.154 --> 01:11:40.580 [SPEAKER_00]: So are all of these people in these studies, they're just maintaining that same status, the whole time, like, you would think some of the people would have changed their lifestyle or be different at the end of the study. 01:11:40.907 --> 01:11:51.870 [SPEAKER_01]: Well, what happened was these were individuals who happened to have their blood evaluated were as part of a test and they were not necessarily given the results. 01:11:51.950 --> 01:11:55.391 [SPEAKER_01]: So they didn't have the opportunity to act on that. 01:11:55.431 --> 01:11:57.452 [SPEAKER_01]: I think that gets to the question, right? 01:11:57.725 --> 01:12:06.889 [SPEAKER_00]: Yeah, yeah, I guess so, yeah, because just Vitamin D is something that you can, I mean, if you want to like really high dose, you could like change pretty fairly quickly. 01:12:07.069 --> 01:12:14.031 [SPEAKER_01]: That's right, and it should be, and it's, it's front and center in this book that why would you not want to know, you know, your Vitamin D level? 01:12:14.131 --> 01:12:15.212 [SPEAKER_01]: It's so easy to fix. 01:12:15.616 --> 01:12:15.916 [SPEAKER_00]: Yeah. 01:12:16.856 --> 01:12:17.277 [SPEAKER_00]: Okay. 01:12:17.577 --> 01:12:17.877 [SPEAKER_00]: Okay. 01:12:18.137 --> 01:12:20.298 [SPEAKER_00]: And then one last like big topic. 01:12:20.698 --> 01:12:34.063 [SPEAKER_00]: I was so impressed with the just how extensive you go into like the pollution and the microplastics and all of these things I think it can be so like the microplastics so how much of the brain is actually plastic do they think. 01:12:34.381 --> 01:12:38.347 [SPEAKER_01]: Well, it's 0.5% so a half of 1%. 01:12:39.308 --> 01:12:44.636 [SPEAKER_01]: If you wanted to ask yourself what that represents, it's a plastic spoon. 01:12:44.996 --> 01:12:51.185 [SPEAKER_01]: So you and I have the amount of plastic found in a plastic spoon in our brains right now. 01:12:51.597 --> 01:13:06.359 [SPEAKER_00]: I will say, so I have, for the longest time, I have been very intentional about plastic, I've been very intentional about eating organic, you know, all, I've been very intentional about all the things and I recently got back a true age test. 01:13:07.439 --> 01:13:10.101 [SPEAKER_00]: And I still had like glyphosate in me. 01:13:10.221 --> 01:13:15.866 [SPEAKER_00]: And like, like all this stuff, I was like, I was like, I try so hard like it's still there. 01:13:16.826 --> 01:13:22.531 [SPEAKER_00]: How much does it actually move the needle to make these changes? 01:13:22.651 --> 01:13:25.913 [SPEAKER_00]: And is it okay if some is still there? 01:13:25.973 --> 01:13:32.058 [SPEAKER_00]: Like if we still have some glyphosate in us and microplastics, like how much change can we just actually make? 01:13:32.378 --> 01:13:33.139 [SPEAKER_01]: It's not a question. 01:13:33.159 --> 01:13:36.762 [SPEAKER_01]: I think I can answer for you right now because we don't really know the answer to that. 01:13:37.435 --> 01:13:46.783 [SPEAKER_01]: So, you know, it's beyond the fact that there's plastic in your brain, plastic in your body, it's what else is involved in that plastic. 01:13:46.803 --> 01:13:56.972 [SPEAKER_01]: We know that plasticizers are the contained things or what is utilized are these forever chemicals that are endocrine disruptors, and that can't be good. 01:13:57.817 --> 01:14:19.106 [SPEAKER_01]: So, what we know is that, yes, as described, these microplastics and nanoplasics make their way into the brain, into the liver, into the kidney, into the gonads, and we know that at least from the experimental studies that they absolutely activate these neuroinflammatory pathways and activate the microglia. 01:14:19.386 --> 01:14:23.448 [SPEAKER_01]: That's, you know, well, we've talked about for our entire time together today. 01:14:24.208 --> 01:14:27.911 [SPEAKER_01]: So we don't want to do anything to activate these microglia. 01:14:28.452 --> 01:14:38.920 [SPEAKER_01]: The other thing they do is they can compromise mitochondrial function, and that is via the connection and mitochondrial function to the microglia cells, very, very important. 01:14:39.021 --> 01:14:48.609 [SPEAKER_01]: So I think that we need to see more of that story, but I think why way to round the results are not going to be good in my opinion. 01:14:49.309 --> 01:15:06.960 [SPEAKER_01]: So I think all the things that people on your program talk about as ways of reducing exposure to microplastics are meritorious because it's not natural to have plastic in your brain with plasticizers that are endocrine disruptors, I can't imagine that's a good thing. 01:15:07.480 --> 01:15:11.603 [SPEAKER_01]: It's not a good thing in the laboratory animal

from the perspective of microglial activation. 01:15:12.083 --> 01:15:16.385 [SPEAKER_01]: and increasing inflammation and threatened, threatening mitochondrial function. 01:15:16.465 --> 01:15:21.107 [SPEAKER_01]: So as far as a good answer for getting rid of it, I don't have one. 01:15:21.267 --> 01:15:24.528 [SPEAKER_01]: I mean, I'm pitched frequently as are you. 01:15:24.628 --> 01:15:28.750 [SPEAKER_01]: I'm sure with the idea of filtering our blood to take out the microplastics. 01:15:29.070 --> 01:15:29.370 [SPEAKER_01]: Great. 01:15:29.930 --> 01:15:30.951 [SPEAKER_01]: What will that do to the brain? 01:15:31.351 --> 01:15:32.631 [SPEAKER_01]: I don't know the answer to that. 01:15:32.891 --> 01:15:34.412 [SPEAKER_01]: I'm not going to speculate. 01:15:35.369 --> 01:15:42.057 [SPEAKER_01]: I think it's, you know, in moving forward, we're all going to have exposure to microplastics and I think you mentioned glyphosate as well. 01:15:42.678 --> 01:15:43.739 [SPEAKER_01]: I think the effort would be. 01:15:44.950 --> 01:15:50.133 [SPEAKER_01]: directed to hoping that we can reduce at least glyphosate with detoxification. 01:15:50.593 --> 01:15:53.195 [SPEAKER_01]: But I think a better effort is to eat organically. 01:15:53.895 --> 01:16:01.200 [SPEAKER_01]: To not live near agriculture concerns where we know they're spraying glyphosate or periquate now more recently and other herbicide. 01:16:01.520 --> 01:16:05.242 [SPEAKER_01]: That is used in experimental animals to create Parkinson's, I might add. 01:16:05.443 --> 01:16:09.005 [SPEAKER_01]: And just your best to get the word out, that this is bad stuff. 01:16:09.935 --> 01:16:13.618 [SPEAKER_01]: and we don't want you to tray our food with this stuff anymore. 01:16:13.858 --> 01:16:15.940 [SPEAKER_01]: And just hope that there's a change. 01:16:16.220 --> 01:16:18.402 [SPEAKER_00]: Yeah, I think I'm just thinking about this. 01:16:18.422 --> 01:16:21.265 [SPEAKER_00]: I think one of the saddest moments for me on the show. 01:16:21.465 --> 01:16:22.846 [SPEAKER_00]: I interviewed Matt Simon. 01:16:22.866 --> 01:16:25.248 [SPEAKER_00]: He wrote a book called a poison like no other. 01:16:25.328 --> 01:16:26.910 [SPEAKER_00]: And it was all about micro plastics. 01:16:26.990 --> 01:16:31.433 [SPEAKER_00]: And that reading that book made me realize just how much everything is plastic. 01:16:31.453 --> 01:16:32.374 [SPEAKER_00]: Like things I didn't think of. 01:16:32.414 --> 01:16:35.217 [SPEAKER_00]: But when I realized, I was like, oh, glitter is plastic. 01:16:35.257 --> 01:16:36.738 [SPEAKER_00]: That was like the saddest day of my life. 01:16:36.838 --> 01:16:37.519 [SPEAKER_00]: I love glitter. 01:16:39.382 --> 01:16:40.003 [SPEAKER_00]: like no. 01:16:41.565 --> 01:16:46.129 [SPEAKER_00]: So I avoid all plastics except I do have my occasional glitter. 01:16:46.250 --> 01:16:46.510 [SPEAKER_01]: Yeah. 01:16:46.950 --> 01:16:50.114 [SPEAKER_01]: Well, I mean, he makes, you know, some

claims. 01:16:50.154 --> 01:16:57.021 [SPEAKER_01]: He said the title of the book is something about that this is a poison like no other. 01:16:57.862 --> 01:17:09.757 [SPEAKER_01]: And we have a lot to learn about micro-possics, but the levels in tissues are increasing year-old year-over-year, aggressively, both micro-possics and then the nanoplasics. 01:17:10.598 --> 01:17:12.079 [SPEAKER_01]: Again, it can't be good. 01:17:12.860 --> 01:17:18.345 [SPEAKER_01]: and we've got to do better, but I, you know, they're almost here to stay. 01:17:18.365 --> 01:17:21.007 [SPEAKER_01]: I wish we could do other things. 01:17:21.127 --> 01:17:21.728 [SPEAKER_01]: And you're right. 01:17:21.768 --> 01:17:26.452 [SPEAKER_01]: They're appearing in place where we don't expect the glass bottles that you buy for water. 01:17:26.552 --> 01:17:36.940 [SPEAKER_01]: Well, take the cap off and run your fingernail under the underside of that cap in the, in the bottle of the, you know, the spring water and you'll feel it's plastic. 01:17:36.980 --> 01:17:39.643 [SPEAKER_01]: Paper cups, they're lined with plastic on the inside. 01:17:39.743 --> 01:17:39.963 [SPEAKER_01]: So, 01:17:41.134 --> 01:17:43.196 [SPEAKER_01]: It's tucked to realize all that. 01:17:43.617 --> 01:17:48.282 [SPEAKER_01]: Can soup the inside has liners that are have microplastics available? 01:17:48.577 --> 01:17:49.978 [SPEAKER_00]: Yeah, it's really shocking. 01:17:50.719 --> 01:17:54.061 [SPEAKER_00]: But on a brighter note, I cannot thank you enough for your work. 01:17:54.362 --> 01:17:56.163 [SPEAKER_00]: This book is absolutely incredible. 01:17:56.243 --> 01:18:09.854 [SPEAKER_00]: And finally, you know, provides a, like a solution, but I am, you know, an answer for what is actually happening here and gives people so much agency and friends, we only barely touch on everything in the book. 01:18:10.275 --> 01:18:17.841 [SPEAKER_00]: Dr. Promutter goes through so many things, like all of the different supplements with, you know, which can possibly help all of these different therapies, the future. 01:18:18.541 --> 01:18:45.208 [SPEAKER_01]: of different mechanisms and or so are different treatments that are being studied and yeah it's it's a very valuable so thank you thank you so much for the work that you're doing I can't thank you enough are you writing another book now are you kidding I can't I can't jump on that just yet I'm just working through this one so yeah it's well no one has asked me that question and I haven't even thought of the answer to that question 01:18:45.743 --> 01:18:50.084 [SPEAKER_00]: Do they come to you because you find an idea and you have to write about it? 01:18:50.144 --> 01:18:51.885 [SPEAKER_00]: Or is it like you decide I wanna write my next book? 01:18:51.905 --> 01:18:52.545 [SPEAKER_00]: What should it be? 01:18:52.785 --> 01:19:01.068 [SPEAKER_01]: I think I get really fascinated with the topic and ultimately, you know, I say to myself, the world has to

know this information. 01:19:02.232 --> 01:19:03.193 [SPEAKER_01]: And that's what happens. 01:19:03.413 --> 01:19:07.797 [SPEAKER_01]: That's what happened with drop acid because who knew this about Euric acid? 01:19:07.817 --> 01:19:08.778 [SPEAKER_01]: We weren't talking about it. 01:19:09.138 --> 01:19:12.041 [SPEAKER_01]: And the microbiome, drop, that was a brain maker. 01:19:12.181 --> 01:19:12.842 [SPEAKER_01]: I mean, who knew? 01:19:12.922 --> 01:19:16.124 [SPEAKER_01]: And who knew about, we didn't have a term ultra-processed food back then. 01:19:16.144 --> 01:19:19.828 [SPEAKER_01]: And who knew about these processed carbs back in the grain-brained days? 01:19:20.388 --> 01:19:35.655 [SPEAKER_01]: So identify these topics, ideas that ultimately I have a feeling I can do a lot with this topic to get the word out to people so that they don't have to experience their father dying of Alzheimer's like I did. 01:19:36.195 --> 01:19:39.096 [SPEAKER_01]: because it doesn't have to be, you know, it just doesn't have to be. 01:19:39.116 --> 01:20:00.321 [SPEAKER_01]: There was a study published by the Lancet Commission in 2024 that described 14 interventions we could engage many of them lifestyle interventions that could be associated with a 50% reduction in the risk of the development of or the incidence of Alzheimer's as it were. 01:20:01.578 --> 01:20:04.220 [SPEAKER_01]: And you know, no one pays attention to that and they should. 01:20:05.081 --> 01:20:07.002 [SPEAKER_01]: So, uh, that's the mission. 01:20:07.142 --> 01:20:08.543 [SPEAKER_01]: So I don't know what the next book will be. 01:20:08.583 --> 01:20:09.404 [SPEAKER_01]: Maybe poetry. 01:20:09.904 --> 01:20:11.025 [SPEAKER_00]: Oh, yes, poetry. 01:20:11.125 --> 01:20:11.665 [SPEAKER_00]: Oh, my God. 01:20:12.346 --> 01:20:15.928 [SPEAKER_00]: It'd be amazing that the Lancers say that's one that's mentioned at the beginning. 01:20:15.968 --> 01:20:17.670 [SPEAKER_00]: That's the one, though, where they didn't include. 01:20:17.750 --> 01:20:18.951 [SPEAKER_00]: You guys wrote in about something. 01:20:18.971 --> 01:20:19.631 [SPEAKER_00]: They didn't include. 01:20:19.831 --> 01:20:20.712 [SPEAKER_01]: You're right about that. 01:20:20.732 --> 01:20:21.112 [SPEAKER_01]: They didn't. 01:20:21.132 --> 01:20:21.833 [SPEAKER_01]: I mentioned diet. 01:20:22.073 --> 01:20:26.296 [SPEAKER_01]: Having you mentioned the mind diet, you know, the work of Martha Claire Morris. 01:20:26.787 --> 01:20:47.412 [SPEAKER_01]: then they didn't mention so we wrote a letter, Dr. Robert Lussen and I wrote a letter to the Lancet saying, oh, we're sure it's an oversight here are a list of references about thumb-line diet about all these dietary interventions, the various studies, and we got a pat on the back saying, well, thank you, but we're not going to publish your letter and have a nice day, but keep reading the journal. 01:20:48.096 --> 01:20:52.418 [SPEAKER_01]: So anyway, you know, you stay in the

baddest box, though, and keep swing in the bat. 01:20:52.578 --> 01:20:53.638 [SPEAKER_00]: Well, that you're doing. 01:20:53.698 --> 01:20:55.699 [SPEAKER_00]: Well, thank you so much, Dr. Promutter. 01:20:55.739 --> 01:20:57.980 [SPEAKER_00]: So everybody, go get brain defenders now. 01:20:58.500 --> 01:20:59.480 [SPEAKER_00]: Everybody, I'm serious. 01:20:59.560 --> 01:21:00.760 [SPEAKER_00]: Everybody needs to read this book. 01:21:00.941 --> 01:21:02.261 [SPEAKER_00]: It didn't truly is life-changing. 01:21:02.741 --> 01:21:04.022 [SPEAKER_00]: Very, very last question. 01:21:04.062 --> 01:21:06.082 [SPEAKER_00]: I ask every single guest on the show this. 01:21:06.282 --> 01:21:08.623 [SPEAKER_00]: And it's just because I appreciate mindset so much. 01:21:08.663 --> 01:21:10.224 [SPEAKER_00]: So what is something that you're grateful for? 01:21:10.464 --> 01:21:11.684 [SPEAKER_01]: I'm grateful for a lot of things. 01:21:11.744 --> 01:21:13.525 [SPEAKER_01]: I'm grateful for my children, my wife. 01:21:14.265 --> 01:21:15.886 [SPEAKER_00]: I'm grateful to be living in this time. 01:21:17.155 --> 01:21:25.864 [SPEAKER_01]: I'm grateful for this skill set that I've been given, because I get to do the things I get to do in terms of my outreach. 01:21:26.685 --> 01:21:30.849 [SPEAKER_01]: So I'm grateful that I have a good mind and that I'm curious. 01:21:30.989 --> 01:21:36.195 [SPEAKER_01]: So it allows me to accomplish things that help me fulfill my goals in life. 01:21:36.470 --> 01:21:37.070 [SPEAKER_00]: Amazing. 01:21:37.110 --> 01:21:38.812 [SPEAKER_00]: Well, we are grateful for that as well. 01:21:38.892 --> 01:21:39.972 [SPEAKER_00]: So thank you so much. 01:21:40.012 --> 01:21:42.674 [SPEAKER_00]: We'll love to have you back in the future and congratulations on the book. 01:21:42.714 --> 01:21:43.415 [SPEAKER_00]: It's incredible. 01:21:43.555 --> 01:21:45.876 [SPEAKER_01]: Do I have to write another book to come back on your show? 01:21:45.936 --> 01:21:47.197 [SPEAKER_01]: Gosh, that's great. 01:21:47.277 --> 01:21:48.358 [SPEAKER_01]: It's great and incentive though. 01:21:49.159 --> 01:21:49.659 [SPEAKER_00]: No, no, no. 01:21:49.699 --> 01:21:51.300 [SPEAKER_00]: I would love to have you back open door. 01:21:51.320 --> 01:21:52.421 [SPEAKER_00]: You can go back tomorrow. 01:21:53.935 --> 01:21:54.876 [SPEAKER_01]: Alright, thank you, Melanie. 01:21:54.936 --> 01:21:55.516 [SPEAKER_01]: You're the best. 01:21:55.536 --> 01:21:56.177 [SPEAKER_01]: Appreciate it. 01:21:56.477 --> 01:21:57.338 [SPEAKER_00]: Thank you, David. 01:21:57.378 --> 01:21:58.138 [SPEAKER_00]: We'll talk soon. 01:21:58.458 --> 01:21:59.279 [SPEAKER_01]: Alright, bye-bye. 01:21:59.459 --> 01:21:59.880 [SPEAKER_00]: Bye-bye. 01:22:00.420 --> 01:22:04.883 [SPEAKER_00]: Thank you so much for listening to the Melanie Avalon by O'Hacking Godcast. 01:22:05.063 --> 01:22:12.209 [SPEAKER_00]: For more information and resources, you can check out my book, What When Why, as well as my supplement line, Avalon X. 01:22:12.469 --> 01:22:16.452 [SPEAKER_00]: Please visit MelanieAvalon.com to learn more about today's guests. 01:22:16.672 --> 01:22:23.197 [SPEAKER_00]: And always feel free to contact me at contact at MelanieAvalon.com and always remember you bought this.