The Ultimate Human with Gary Brecka - 306. The Alzheimer's Drug With a 25% Brain Bleed Risk - Dr. David Perlmutter

Starting point is 00:00:00 Alzheimer's is an almost uniformly fatal condition. The third leading cause of death in adults in America. There's a lot of theories around Alzheimer's and accelerated brain aging, but many of them point to insulin resistance and high blood sugar as one of the hallmarks of accelerated neurocognitive decline. 90% of America's pre-diabetic patients don't know it. Because you get your annual blood work, you get a pat on the back. Well, you're not diabetic yet.

Starting point is 00:00:25 Go home and hope for the best. I really reject that in the face of some. 7.6 million Americans now diagnosed with Alzheimer's, with being pre-diabetic, being a huge entree to that event. I think there are a lot of people at my age that are dealing with aging parents, and I'm hell-bent on turning this around for my mother and to the extent that I can prevent it for other folks

Starting point is 00:00:46 like my kids, that's a service that I think is well met. I'm hell-bent on getting this message out that you could rewrite your destiny as it relates to your brain, and you absolutely can do it and you just need the tools. In these conditions like Alzheimer's, Patients are not losing their memory per se. They're losing access to their memory.

Starting point is 00:01:02 What do we do now to try to restore that access? You know, ultimately, I think well beyond what I described here is... Hey guys, welcome back to the Ultimate Human podcast. I'm your host, human biologist, Gary Brecker, where we go down the road of everything, anti-aging, biohacking, longevity, and everything in between. And today's podcast guest is a very, very, very special guest to me. He doesn't even realize this.

Starting point is 00:01:40 But in the 300 plus episodes that we've done on The Ultimate Human, only one other time have I used this next phrase that I am sitting down with someone that I consider one of my early mentors in this space. The first time I used that was with Mark Hyman because I had read most of his New York Times best-selling books. and in 2014, I read a book that this gentleman authored called Grain Brain, and it entirely and permanently changed the trajectory of my career. So Dr. David Perlmutter, welcome to the podcast.

Starting point is 00:02:14 Well, I'm delighted to be here today. It's very special to be here, too. I love this area of the world. It has a lot of meaning for me. Yeah, you know, I learned something very special before the podcast today. I walked into my kitchen, and he was FaceTiming with my father-in-law, and it turns out that my wife's father-in-law, built your doc 40 years ago.

Starting point is 00:02:33 That's right. That's a wild connection that we have, but the working years have been a naples for a while. It's a small world, though. Yeah, who knew? It's a small world. But I read Grain Brain. I want to say you wrote it in 2013,

Starting point is 00:02:47 but I read it in 2014. So, yeah, it was published in 2013, wrote in 2012, obviously. And, you know, that book focused, I think, on something that's now pretty well understood and embraced, that eating a diet that features a lot of highly processed carbohydrates is a bad thing for the brain. That was my contention back then.

Starting point is 00:03:09 And, you know, it was a great success. The book was a great success, but I got a lot of heat from my colleagues. I mean, what do carbs have to do with the brain? How could you make such a statement? We didn't have the term back then of ultra-processed foods. Right. Now, of course, that's what we're talking about. And an ultra-processed carbohydrates being under that umbrella.

Starting point is 00:03:28 and now we see really great data coming out that higher consumption of these foods that are modified such that they're going to raise your blood sugar, threaten the functionality of your insulin, and at the same time are devoid of things that you need like dietary fiber to nurture your microbiome, that these happen to be really threatening for your metabolism. And guess what? The brain is intimately involved with metabolism, either being supportive or being destructive. And, you know, I'm going through this right now. I've been very public about this on my platform with my own mother.

Starting point is 00:04:04 And, you know, I'm upset with myself in a lot of ways because as I really peel back the layers of the onion, she was hyperglycemic or high glycemic, you know, insulin resistant and pre-diabetic for almost 20 years that we can go back and find. And, you know, there's a lot of theories around Alzheimer's and accelerated brain aging, but many of them point to insulin resistance and, you know, high blood sugar as one of the hallmarks of accelerated neurocognitive decline. I wanna stop you right there,

Starting point is 00:04:44 and I want your audience to remember what you just said, because you said something, I think that is fundamental. You said for 20 years, long before her cognitive impairment was noticeable. Yeah, but she didn't have, diabetes, which is why they didn't treat it. It doesn't matter. Yeah.

Starting point is 00:05:00 That's why we're here today. That's the discussion I think that we are going to have today, and that is that when you begin to have these cognitive issues, forgetting why you walked into the room, the Wi-Fi Code, the grandchildren's names, whatever it may be, that situation has been brewing for decades. So that's what our target then needs to be. It's the people in their 30s and 40s who are watching us right now thinking, well, they've got time because, well, Alzheimer's begins in your 70s, it does not. That's when the clinical manifestations begin, and that's when modern mainstream Western medicine begins to think,

Starting point is 00:05:36 oh, there's something we need to do. I'm going to tell you a quote from an 81-year-old man, who was the oldest person to sign the Constitution of the United States of America, and actually sign not only the Constitution, but the Declaration of Independence, Benjamin Franklin. One of his famous quotes is an ounce of prevention is worth a pound of cure. Oh, yeah. We are focused in America, to be fair, on the pound of cure. We're focused on the development of drugs to take care of people to cure their illnesses when just giving them the tools to prevent them 20, 30, 40 years prior to their onset or to the manifestation

Starting point is 00:06:17 is really makes sense from an economic perspective. It makes sense from a health and longevity perspective. and it absolutely makes sense from an emotional perspective too, knowing fully what you are experiencing right now because I've been there. Yeah. And we're now trying to backtrack and catch up for the last two plus decades. And it may have been even longer. We just have data from 20 years ago and knew that she was pre-diabetic.

Starting point is 00:06:50 But never really tripped into the full diabetes range. so never really got care for it. I mean, maybe in some ways had she done that, there would have been a lot more attention. Well, you're talking about a third of American adults are pre-diabetic. And here's the gripping part of that statement and it fits perfectly with what you're describing.

Starting point is 00:07:06 90% of America's pre-diabetic patients don't know it. Right. Because you get your annual blood work. You get a pat on the back. Well, you're not diabetic yet. Go home and hope for the best. Right. And do whatever it is you're doing.

Starting point is 00:07:21 I really reject that. I really reject that in the face of 7.6 million Americans now diagnosed with Alzheimer's, with being pre-diabetic, being a huge entree to that event. We've got to pay attention. We owe it to people to call this out and to really just sort of challenge this notion that annual blood work is enough and the idea of being in the normal range is something we should be thinking is a good thing. Or just not having disease.

Starting point is 00:07:52 Right. I want everyone I relate to to be in the optimal range. I want to optimize health and therefore, answer prevention worth a pound of cure. Keep these people healthy and recognize that, again, the seeds are sown metabolically for developing Alzheimer's in your 30s and 40s and 50s. It doesn't just happen.

Starting point is 00:08:13 There's something called a heart attack. You are perfectly fine. You're walking down the street one day and all of a sudden this thing out of the blue comes and attacks you, narrows, shuts down your LAD and down you go. That's not how it worked. It didn't just attack you out of the blue.

Starting point is 00:08:30 You've been dealing with that for an awful long time that narrowed your coroners. So, you know, this is the mission. And I think our time together today is to really raise up the sense of empowerment that here's the knowledge and here's what you need to do. Here's how you can keep your brain healthy. If you live to be age 85, and I'm sure that's your plan,

Starting point is 00:08:53 and I'm sure that's the plan of everybody watch this right now. Right. Your risk is 40 to 50%. That's basically a flip of a coin of becoming an Alzheimer's diagnosed individual or not. And the purpose of our time together right now is that you can influence that risk dramatically. and the time, as John Kennedy said, the time to fix the roof is when the sun is shining. Right. Wow.

Starting point is 00:09:22 You know, do you subscribe to the fact? I mean, some folks will say that Alzheimer's is type 3 diabetes, insulin resistance in the brain. And I don't think Alzheimer's is one thing. They're genetic predispositions. There are lots of, I guess, multifactory. We've got a lot to talk about today. She was, you know, that's a term.

Starting point is 00:09:42 And it's a term, I think that's a bit myopic. because it's more than just insulin resistance in the brain that plays an important role. But insulin isn't really having a huge effect on a lot of the brain. There are four major areas, the hypothalamus, the hippocampus, the prefrontal cortex, and the olfactory bulb. Why is that important? It is important because those areas are involved in Alzheimer's, the olfactory bulb. Why do Alzheimer's patients often lose sense of smell early on, even before their cognitive dysfunction becomes manifest.

Starting point is 00:10:17 The hippocampus, their memory center, of course, central player as it relates to Alzheimer's. The hypothalamus, yes, Alzheimer's patients become metabolically dysfunctional, being metabolically challenged with insulin resistance, sets the stage for it, but at the same time, the brain becomes,

Starting point is 00:10:37 disregulates metabolism from the hypothalamus, worsening the problem, and finally the prefrontal cortex, I'm pointing to my forehead because that's where it lives, allowing us to carry out purposeful, what we call executive function. Planned activities, planning for the future, thinking about outcome, relating to other people,

Starting point is 00:10:56 recognizing what I do to myself today might affect me tomorrow. Those are fairly sophisticated human attributes that begin to decay as Alzheimer's manifest. So those areas of the brain basically require insulin for their functionality. other areas of the brain, not so much. But beyond that, insulin is more important than just helping regulate blood sugar and drive

Starting point is 00:11:22 blood sugar into a cell for metabolism. Insulin in the brain is what we call atrophic hormone. You and I had a talk over lunch about BDNF, brain-derived neurotrophic factor, atrophic hormone. And in a very real way, insulin acts in the same way nurturing neurons, nurturing synapses. and, you know, in that regard, we need functional insulin in the brain. So the idea is then if this insulin lack of function gains the moniker type 3 diabetes for these reasons, I can live with it, but that has prompted research into the administration of intranasal insulin to help correct the problem or override the problem.

Starting point is 00:12:06 And I have mixed feelings about that. It's the reason that one reason I sort of reject it is because why do we now give insulin for type two diabetics? I don't fully understand it. They already have very high insulin levels, but the insulin isn't working because their blood sugars have been elevated for so long. So one of the earliest markers that we want to look at is fasting insulin level because that predicts that your blood sugar is going to raise or rise, I guess, would be. more appropriate, but, you know, the idea of giving insulin, well, it'll bring the blood sugar down, no question, but we've got to do better than that. I mean, we've now seen over the past decade how dramatically effective in a type two diabetic,

Starting point is 00:12:52 a ketogenic diet can be. Yes. To reestablish insulin functionality, not insulin quantity, but the function of the insulin that we already have. The sensitivity of the insulin itself. You bet. The function of that insulin. Go ahead. Well, I was going to say, what is a good fasting insulin level? I mean, because when people get a blood panel and they've got fasted glucose, hemoglobin A1C, three month average of the blood sugar, and then insulin.

Starting point is 00:13:16 Between three and five. Between three and five. And that is really low single- Yeah, it is. It is. And you and I are talking optimization here today. Yeah. We're talking pre-Alzheimer's. Right.

Starting point is 00:13:27 You know, what the heck is that term? Well, we know pre-diabetic because the blood sugar is starting to rise. Well, we have a pre-alzheimer's when you are metabolically compromised. How do you know? you know because your blood sugar's elevated, your fasting insulin's coming up, your A1C is elevated, your waist to hip ratio is increasing,

Starting point is 00:13:46 your belly is getting bigger, your blood pressure is going up. These are metabolic issues that are changing the function of your brain's immune cells and creating a brain environment that is threatening to your synapses. Maybe I wanna unpack that a little bit more. Yeah, no, I definitely,

Starting point is 00:14:04 this is the route that I wanna go because I have a very selfish reason for having you on the podcast today. But also I think there are a lot of people that my age that are dealing with this, with aging parents. And I'm hell-bent on turning this around for my mother and to the extent that I can prevent it for other folks,

Starting point is 00:14:23 like my kids and their kids, you know, that's a service that I think is well met. And it's certainly for you. But can you imagine putting your kids through your cognitive decline, what that would be like for them. You're getting a sense of that right now, what you're going through,

Starting point is 00:14:43 and you don't want your kids to go through that. That's exactly it. You know, I watch my brilliant brain surgeon father die of this disease. Really? While I am a practicing neurologist and I had nothing to offer him. Wow. And it's challenging.

Starting point is 00:14:59 It really is challenging. What do you do with that? Right. And then you just use a term hell bent. So I'm hell bent on getting this message out that you could read. rewrite your destiny as it relates to your brain. You absolutely can do it and you just need the tools.

Starting point is 00:15:13 And your audience already knows what these tools are to some degree. We'll talk about some leading edge kind of stuff in a minute. But your very first podcast dealt with metabolism. Yes. Think about that. And we now have a term called immunometabolism, the relationship of the immune system to metabolism. Holy Toledo.

Starting point is 00:15:35 How does that work? Yeah. We know intimately that your brain's immune system is responsive to your body's metabolism. Your brain's immune system made up of what we talk about in this book, the microgleal cells, allows those microgleal cells to nurture your synapses, to love your neurons, to shore up the blood-brain barrier, or those microgleal cells, when your metabolism is threatening, will shift to becoming the evil twin. Wow. And when those microglue cells become the evil twin, they destroy synapses.

Starting point is 00:16:10 They cause lack of connection in the brain. Loss of connectivity. They threaten the neurons and they destabilize the blood-brain barrier. That shift of those immune cells from being what we call M2 supportive brain defenders to being destructive is dictated by their metabolism. And their metabolism mirrors your body's metabolism. Wow. Home run. Wow.

Starting point is 00:16:36 So, you know, like the notion that all cancer, regardless of its former origin, was at one time a healthy cell. And what happened to that cell? It shifted its metabolism. And that shift in metabolism now produces a cell that takes as many lives, second only to cardiovascular disease. And third on the list? Alzheimer's. Yeah. Alzheimer's.

Starting point is 00:17:03 about that. Wow. Who, Alzheimer's is an almost uniformly fatal condition. Yeah. The third leading cause of death in adults in America. Wow. So let's contextualize this a bit, that we're spending, you know, 360 billion with a B on caring for Alzheimer's patients for a disease that I will tell you today is largely preventable. Now, there's a genetic predisposition. So are you talking about? about in the non-predisposed population. I am talking about those individuals more specifically than you can imagine. Wow.

Starting point is 00:17:40 So we do know that if you carry one or two APO-E4 alleles, as many of your audience I'm sure understands because they've had their blood work done, that you have a, as you characterize it, predisposition, great word, not destiny. Right. Presidist is not destiny. Right.

Starting point is 00:17:57 So we see the studies now that indicate that dramatic lifestyle changes can absolutely offset that genetic predisposition. I mean, these people get back their genetic stuff with the printout who says, basically put your wagons in a circle because you're in deep trouble.

Starting point is 00:18:12 Right. And I'm here to say to, you know, all of your audience, that is just not true. And I'm talking to 25% of your audience right now. Wow. Got their genetics back, saw the APOB4 and said, I'm basically screwed.

Starting point is 00:18:27 It's just misinformation. So there's so much that can be done. People ask me health questions every single day about their labs, their sleep, their supplements, their genetics. I want to help every single one of them. And that's why I built Just Ask Gary. It's an AI trained on everything I know, including my protocols, my research, and my methodology. You ask the question, you get my answer. Any time of the day. Go to the ultimatehuman.com forward slash AI and check it out. Now let's get back to the Ultimate Human podcast. So I want to get very specific with you and really get deep into the book. but what does that lifestyle look like, 30s, 40s, I'm in my 50s.

Starting point is 00:19:07 I believe that I'm living it now, but the previous two centuries, not so much. So I've got to over-correct. No, I know that feeling very well. We were talking real, yeah, I mean, even the head trauma part. Yeah. I remember lying on the mat being counted out by the ref, because I couldn't get out after I got kicked in the head in a, match of some sort back in the day.

Starting point is 00:19:33 Like a karate tournament? Yeah, it was, before they had MMA, they had, it was full contact karate. And I, you know, nothing can harm me, right? Sounds like a great idea. I was a great plan, you know. And no headgear. It was a great plan. No head gear at all.

Starting point is 00:19:47 And, and there were several other events that I, you know, had a, yeah, but anyway. And my lifestyle choices back in the day when you were just like impervious to these events. They accumulate over time. They manifest in the changes in your metabolism. You can watch it happen if you're looking. So that's a point I want to make. You really want to be metricizing. You want to wear your aura ring or Apple Watch or whoop, whatever it may be,

Starting point is 00:20:14 and find out what is the duration and quality of your sleep. Very important. What is your blood sugar doing? Where a CGM continues glucose monitor from time to time. Get your blood work done. You know, you can do that without a doctor now and get that information. then you challenge yourself with the question, well, what do I do with this information?

Starting point is 00:20:34 You know, we'll talk about what that, and I put parameters in the book about what things should look like. But, you know, ultimately, I think well beyond what I described here is availing yourself of a more personalized medicine approach in a clinical situation that's using AI to determine what's best for Gary Brecker that would be different than David Perlmutter. You want to know that. Right, very specific, personalized medicine.

Starting point is 00:21:01 That's state of the art right now. And it's widely available, by the way. Absolutely, widely available. So let me give, I didn't answer your question. Yeah, when I got that. So the question was, then what are the things that shift these microglial cells? And we mentioned metabolism. So all the metabolic issues will shift microglia cells away from being supportive to being destructive.

Starting point is 00:21:22 That is the fundamental now across the entire spectrum of neurodegenerative conditions. conditions, Alzheimer's, Parkinson's, MS, multi-system atrophy, progressive supernuclear palsy, long COVID, post-traumatic stress disorder, major depressive disorder. Who knew? These are not considered neurodegenerative conditions, but they shift the microglia and set the stage for brain degeneration. We've got to pay attention to that. So this understanding of immunometabolism, the relationship of the brain's immune system. In fact, your entire body's immune system to the state of health of your metabolism

Starting point is 00:22:04 is profound. It's a bit iconoclastic, and it is certainly empowering. I notice you don't call it autoimmune. Like autoimmune microglial. Well, and I was just asked that question because it's not a classic rheumatoid arthritis, systemic lupus serotonosis,

Starting point is 00:22:29 ankylosing, spondylitis type of Crohn's disease. It's not antibody to a neuron. It's not antibody directed. It's not a molecular mimicry where there's on a cell surface of any particular tissue that the immune system is then directed to. So that part of the immune system

Starting point is 00:22:48 is directed and causes problems. But in a very real sense, it is your innate immune system going awry. So it's auto in that it's contained within you and it's certainly an immune issue. Importantly though, and we should open this up later on. Yeah.

Starting point is 00:23:06 I think in our third hour, maybe in the fourth hour. We'll get there. You're in for a long... We still gotta go back to Brain Brain, so that was 2013. I know. I'll pick it up from there. Yeah. But it's interesting to me,

Starting point is 00:23:15 and then I'll get back to my point, that this explains grain brain. Because when I wrote GreenBrand, it was about the correlations between elevated blood sugar, elevated A1C, diet, issues and risk for Alzheimer's. Got that, but I didn't know how it happened.

Starting point is 00:23:31 I didn't know why mechanistically. Mechanistically, now we get it. Now it all comes together. And I'm grateful at 71. Finally, the pieces came together. I wrote a book years later, several years later, called Brain Maker. And I had the conclusion, strange as it may be,

Starting point is 00:23:47 that there's a relationship between, get ready for this, gut health and brain health. I know, the gut-brain connection. So talked about that. I read that too, yeah. Similarly, you know, there was a lot of pushback. But anyway, explains that too. Because part two of our story away from immunometabolism is the effect of inflammation from anywhere in the body on polarizing these microbial cells away from being brain defending, supportive, to being the evil twin, to being destructive.

Starting point is 00:24:20 Inflammation, the molecules of inflammation called inflammatory cytokines, can come from the lungs when we're breathing PM2.5s from wildfire smoke can come from a leaky gut because of dysbiosis or changes in our gut bacteria can absolutely come from the mouth

Starting point is 00:24:38 when we have periodontal disease a powerful risk factor for Alzheimer's why does that happen? Now we understand. The shift-tental cavities. You bet. Not as much to carries as the periodontal disease,

Starting point is 00:24:51 the gum disease, carries as well. I mean, it's just another indication of poor dental health. So while we now understand all of these relationships, the empowering part is, okay, we'll talk about what we should be doing for people's dental health and gut health and reducing your exposure to PM2.5s by virtue of the fact that you're breathing 20,000 times in 24 hours,

Starting point is 00:25:15 maybe we should pay attention to the quality of that air. We had a long discussion about what you're doing right here earlier, and hats off to you for doing that. We do the same thing. Yeah. It's that important. I mean, you're paying attention to the quality of water, air, especially these days. You know as well as I, what's going on.

Starting point is 00:25:34 Certainly North America is scary. Well, no, in the air quality with respect to wildfire smoke and in Europe as well. Wildfire smoke, I mean, aluminum. I haven't tested the air in quite a while, but I tested the Miami-Dade water. And, you know, everybody talks about the fluoride, the chlorine. It was all of the PFAs and the other things that I found in there. heavy metals, pharmaceuticals, that just made me really freak out

Starting point is 00:26:01 and so really aggressive water filtration. I'm not going to say that's a broad stroke, but I'm not going to play it down either. It's really important. You know, the goal for me is if we can get people even a few on-ramps, here's what a better brain diet looks like. Yeah, this is exactly where I want to know.

Starting point is 00:26:20 Take out a pen, guys. Yeah. Get some quality sleep tonight and moving forward. Here's why you absolutely... I had 100% sleep score last night. Oh, did you? Yeah, I showed me that.

Starting point is 00:26:30 Yeah, I showed you my HRV. I was proud of that. Yeah, 70-HRV, that's incredible. These 70 years old... That's one year less than my age. Yeah, it's correct. You know, you should say, if you're a golfer, you should golf your age.

Starting point is 00:26:43 I'm not a golfer, but I want to have your HRV. But, you know, the point is that these are powerful inroads to recharting your brain's destiny. and the idea that exercise, yeah, you want to be pumped up. You want to look good. You want to feel great. You want to sleep better. It's why exercise.

Starting point is 00:27:02 Yeah, all those things. But it's one of the most powerful tonics for brain health. There are hacks left, right, and center. And some of them have great merit. We talk about them in the book. You know, what's the future of would rapamycin be something that's in a brain healthy program? What about metformin? What about red light therapy?

Starting point is 00:27:21 What about hyperbarics? we can talk about those things, but the broad strokes are what we've just mentioned and do them. You've got to do them. Exercise. Yeah. And in particular, any type of exercise.

Starting point is 00:27:34 Weight training, I will say that the most important part is getting started. Yeah. But it's often a question of, well, which is better for my brain is that the aerobic part of the resistance training. And there was recently published a meta-analysis of 32 different studies,

Starting point is 00:27:54 encompassed thousands of patients, and evaluated what was the cognitive outcome in individuals based upon if they were dedicated to their aerobics program, whether it involved a dedicated aerobic program or doing aerobic exercise by playing pickleball or whatever it would be, or those who did resistance training, weights, tension, bands, machines,

Starting point is 00:28:17 or even those who decided to do both. and by far away the winner was both. Really? Absolutely. And it makes sense now that you read their conclusion and why, but you think about it a little bit and we'll unpack that a little bit. But I just want to say, and we talked about this at lunch, that I want to add to that.

Starting point is 00:28:36 Okay, people are going to do, well, I do the rubbish, I do whatever, resistance, but flexibility and balance. Why? So you don't get injured. Those are the two, I would say, probably my weakest points. You know, I'm not very flexible, and I never do any balance work per se. But your wife has great balance. She has amazing balance.

Starting point is 00:28:57 I know, but you can train balance. And the reason you want to train balance is so you don't fall. Okay. And you're not thinking about it right now, but at the older guy here. My dad's broken an arm and hip in the last year. In my house. People in my age category, I'll leave it at that, fall and may not know how to fall. first of all and fall because they don't have good balance.

Starting point is 00:29:22 I don't know that you can train people how to fall. That's something you learn earlier in life. Various things you can do where you learn how to fall. Because I used to fall not frequently, but on occasion when I was running, and there's ways of falling and you can not get hurt. Yeah, yeah. I fell once in front of, there's not part of our talk, but anyway, in front of a large crowd in Washington, D.C.,

Starting point is 00:29:48 I was actually invited to speak to the International Monetary Fund about the health implications of Alzheimer's moving forward, and guess what, is a preventable, largely preventable situation? And I took a dive. There was a huge crowd. In front of the audience? No, no. Other audience that I think in front of one of the sites there.

Starting point is 00:30:05 And I was really, you know, going fast. I was training for a marathon, I think, the time. And I took a terrible dive. But I rolled and I got up on my feet. There's a scene. in Pee-Wee-Herman's great adventure, we crashes his bike, he gets back on, he says, I meant to do that.

Starting point is 00:30:20 I didn't say I meant to do that. Yeah, that would have been, but I was thinking that. That would have been like sticking the landing. Oh, I know. Through your hands up. It's true when you mess up, if you could pull it off, yeah.

Starting point is 00:30:31 Yeah, if you actually get points. So those are probably, that's probably from your karate days, you know, because you learn that how to tuck your head and kind of roll you onto your shoulder. Yeah, there's other, I think judo teaches you more how to fall.

Starting point is 00:30:43 Yeah, but, yeah, various martial arts will teach you how to fall. I think learning how to fall is a pretty darn good skill to have. And people don't really train that. But, you know, when you're a kid, you're always falling down and either get a hurt or not, so you learn pretty quickly. Football teaches you how to fall, too. Tackle football.

Starting point is 00:31:00 Okay. So aside from tackle football, so string training and obviously aerobic training on a consistent basis over a prolonged period of time. Let me finish that thought, though. Sorry to interrupt you. But in that study, the people who derive, the best benefit were those who had already cognitive impairment to some degree, and also the group

Starting point is 00:31:20 65 years and older. So you're just about to ask me, is it ever too late? Right. It is absolutely not ever too late. So starting a strength and resistance training program now with some flexibility and balance moved in and some cardio component, and doing that consistently, minimum three days a week. That's right. And calling it like it is, losing muscle mass is a very big risk. for metabolic issues, therefore directly related to Alzheimer's and cardiovascular disease, but also directly related to risk for Alzheimer's, losing muscle mass called sarcopenia. Wow.

Starting point is 00:31:57 And I tell you, N of 1, and not that there's not plenty of data that, supports this. The older you get, the harder it is to keep muscle mass. You have to work harder. It's more time. It's paying attention to adding creatine to your regimen, testosterone perhaps, to your Regimen, all of the things that you've talked about on the podcast, you've interviewed the experts, it all makes incredible sense. So you're a fan of creatine.

Starting point is 00:32:23 I actually, that was one of the areas I wanted to talk to you about with, you know, there's some big claims out there around creatine. I was curious what you felt that data supported in terms of cognitive function, crossing the blood-brain barrier, mitigating sleep deprivation, those kinds of things with creatine. So let's unpack that a little bit. The systemic creatine that you have doesn't really make its way to the brain to any significant degree.

Starting point is 00:32:52 It does. But the brain makes its own creatine. The creatine that's manufactured in the liver and the kidneys works for the rest of your body, definitely works for your muscles, and that sort of is this relationship that we're trying to take advantage of.

Starting point is 00:33:07 If you can raise your blood level of creatine, though it may not make its way fully to the brain, you're supporting muscle growth. And that's what you want to support your brain. Why? Because your muscles are an endocrine gland. We begin to get our arms around that. What is that all about?

Starting point is 00:33:24 Like a glucose sponge. Well, not just that, but, you know, the definition of the endocrine gland, the thyroid, the pituitary, the adrenals, is that these are organs that make chemicals that go elsewhere and do other things. You know, there are thyroid receptors on all of your tissues. The adrenals stimulate, you know, various tissues during times of stress. That's one part of the adrenal. And pituitary certainly has effects throughout the body. The muscles do exactly the same thing. They create chemicals that have a huge impact on our metabolism, on regulation of our blood sugar.

Starting point is 00:34:00 And even irisin, one of those myokines, myo-muscle kind moves, irisone being one of those chemicals, makes its way to the, the brain and stimulates the production of something called brain-derived neurotrophic factor. We talked about it earlier before we went on camera. That is something we want to have as much of as possible because it amplifies the growth of new neurons, amplifies the formation of synapses so our neurons can talk to each other, and it's generally just a good player in the brain. So the more of that, the better we bring that about by exercising.

Starting point is 00:34:40 So who wouldn't want to do that? Other things input to BDNF as well. There are some research protocols to increase BDNF with various interventions, but even omega-3s, DHA in particular, AMSA BDNF production. So this isn't a direct effect of muscle activity to the brain. It's an intermediary effect of this erosin chemical

Starting point is 00:35:07 produced by muscles making its way to the brain. interleukin 6, which we've been saying for years, oh, that's a bad inflammatory cytokine made when muscles are active. And in some ways, it is a bit pro-inflammatory, which is probably a good thing as it relates to exercise. We need a little inflammation as a hermetic stress to amplify recovery and repair.

Starting point is 00:35:31 But that said, this interleukin-6 cytokine is actually the key for how muscle activity stimulate something called AMP kinase. Now, I don't want to be too technical about all of this. But AMPK. But AMPK is a powerful target for our mitochondria, allows the mitochondria to be removed if they're defective. It amplifies mitochondrial biogenesis,

Starting point is 00:35:56 the growth of new energy producers, the mitochondria, through activation of something called the PGC1 Alpha pathway. But the point is exercise through aisle 6, through ampicinase, PGC1 alpha, is good for the mitochondria. Let's just say exercise then connects to mitochondria. That hormetic stress causes mitochondria to improve its metabolic function and potentially even increases mitochondrial density, right? The proliferation of the end up.

Starting point is 00:36:24 It absolutely does. How can we see that? You can actually visualize that. It's when the normal fat gets converted into brown fat, the metabolically favorable kind of fat. And it's brown because it has more mitochondria. Who knew? I knew it had more mitochondria.

Starting point is 00:36:45 That's why it's brown. Because it was brown. It was brown. It was brown. But let me rein this back to our time together today. Yeah. Which I'm really enjoying. Yeah, I am too.

Starting point is 00:36:54 I really am. You know, we knew each other kind of peripherally. Yeah. Anyway, and that is that the shift of these microglial cells from being supportive to being destructive from being brain defenders to being brain destroyers is characterized by a shift in their mitochondrial function. When the shift happens, their mitochondrial function basically evaporates almost fully.

Starting point is 00:37:24 Now they're using glycolysis, another energy-producing pathway, far less effect. Interestingly, what cancer cells use, we talked about them in the hallway. Blycoercoration. They're using a far-reliac. less efficient way of making these ATP energy molecules. So everything that we have talked about

Starting point is 00:37:44 about exercise in the mitochondria just now, amply kinase and all of that, and that we will talk about that deals with mitochondria, the play here is that when you improve mitochondrial function, you're protecting the supportive brain defender, microglia, in your brain. Let me tell you how vast this becomes. I mentioned earlier a laundry list of neurodegenerative conditions that are characterized by this shift of the mitochondria away from being supportive to being destructive. Which is the hallmark shift of these microglyle cells

Starting point is 00:38:21 going from being reparative to destructive. Exactly. We can image that in living humans now. In the brain. In the brain. We can absolutely do scans. Is that a Q-E-E-G? No, it's called a TSP scan. And TSPO is a marker that is much more expressed on the mitochondrial membrane of the M1 damaging microglial cells in comparison to the supportive microcliol cells. So when you do a TSPO scan of an individual, if it lights up, it's telling you those

Starting point is 00:38:58 microglia have shifted. And in my lectures, I show what a normal brain versus. versus an Alzheimer's brain, TSP scan looks like. Let's look at that image right now. Yeah, yeah. And if you see- If you see on the left side of your screen, what you're seeing right now is the normal brain.

Starting point is 00:39:15 On the right side of the image, that's the TSP image in the Alzheimer's brain. It's light up. What you're seeing light up here is evidence of the microglia being activated into their destructive condition and what you're actually imaging is this TSPB binding to a unique resell

Starting point is 00:39:34 on the surface of the mitochondria of these activated microglial cells. Let's look at this next slide, because I think it's really compelling. What we're seeing here is a list of all of the neurodegenerative and other conditions in which TSPO imaging is positive. Meaning, if you look at this list, these are all diseases and disease states

Starting point is 00:39:59 in which the microglia have shifted to becoming destructive. destructive. Wow. Microglia shifting to becoming destructive is something that we now have the tools to target. And most importantly, we should be living our lives, choosing lifestyle interventions such that we can keep our microglia away from being this TSBO image type of situation where they're shifted already being destructive. We have the tools to make that happen right now. And what are the tools once you are in that situation, because a lot of what we've talked about is what we do to prevent that situation.

Starting point is 00:40:36 Exercise, controlling blood sugar, getting, you know, making sure that you don't become insulin resistant and to the extent that you are managing insulin resistance, omega-3, high omega-3, fatty acid intake, I would imagine a diet, a lower glycemic diet. But now that we find ourselves in the situation like I'm in,

Starting point is 00:41:00 with my parent, where I haven't done that image, but I assume that it would light up. I've seen the hypoactive areas of the brain on QEEG. And so what do we do now to try to restore that access? Because one of the fascinating things that we talked about before the podcast was that even in these conditions like Alzheimer's, patients are not losing their memory, per se. They're losing access to their memory.

Starting point is 00:41:29 how do we restore access or can we? Well, we give you the tools, and I will walk you through it, but far be it from me just to sit here and say, well, this is what I think we should do. Let's talk about a study that was published last year in the Journal of Prevention of Alzheimer's. Actually, no, that's not worth published, but it was published by, we'll cover that study in just a moment

Starting point is 00:41:53 because I think it's really very relevant. This study was carried out by Dr. Rudolph Tansy at Harvard, along with Dr. Dean Ornish, an interventional trial on 51 patients who were diagnosed with Alzheimer's disease, an intervention that lasted around 20 weeks. What did they do? Yes. They changed their diets. They increased their exercise. They managed their stress. And what did they find? That's it. Chimes their diet. Increased exercise, managed stress. Right. Okay. Normally in 20 weeks, Alzheimer's patients decline.

Starting point is 00:42:32 In 20 weeks, Alzheimer's patients on the newer beta amyloid drugs decline. We're going to talk about that because it's really, it's fundamental, I think, to this whole discussion that these drugs are ineffective. We'll talk about that. They're focused on in the endpoints, like the neurofibrillator. Bio, exactly, which is the beta amyloid, which is unfair. We'll get there. I have a few things to say about that. Yeah.

Starting point is 00:42:59 That's true. I know you do. But what they found is that in 70% of the individual that underwent this intervention, their cognitive decline either stopped, which no drug can do, or improved. Their cognitive function improved.

Starting point is 00:43:18 I want that one to stew for a moment. Because most of your audience has not heard of that study. and they should have. Most of your audits has heard about the idea of, oh, we've got a brand new drug that targets beta amyloid for mom or dad when they start to have cognitive impairment. And we'll talk about, no, I'm going to talk about that. Right.

Starting point is 00:43:37 But I think that it was very telling. It was a small study. Granted, it was a small study. But let's wind the clock back a little bit to individuals who are at risk because of their metabolic issues, a much larger study published in the Journal of the American Medical Association. and it was called the pointer study that was completed last year. This was more than 20,000 people, a two-year intervention where they did the diet,

Starting point is 00:44:05 the exercise, stress mitigation, and had them doing cognitive training using a particular app, Brain HQ. They had two arms. One arm got these recommendations and did this type of training, but had very aggressive interaction with people in the study. During the two-year study, 18 times per year, 36 total. Meetings virtually or a person, how are you doing, what's a diet like, how's the exercise coming along. The other arm had the same programs. I mentioned these were older ages, right? That's an important point. So a lot were deconditioned. Well, not just deconditioned, but these

Starting point is 00:44:42 were people selected because they were at risk for Alzheimer's because they are metabolically compromised, cardiovascular disease, overweight, a six-year-old. 65 and older. Okay. So they're already set up for Alzheimer's. They're well on the continuum. So the other arm didn't get the handholding, if you will, the 36. They got a total of three a year, so a total of six meetings with people.

Starting point is 00:45:07 How's it going? Are you doing the program? So they pretty well got the program and almost do your best and we'll talk to you later. The end of the program, they evaluated these individuals with cognitive assessment. and these people are expected to decline cognitively. Because of their age, because of their metabolic derangement, if you will. No, they didn't.

Starting point is 00:45:32 They didn't even stabilize, but they dramatically improved across various domains. Wow. Now, that's what they found in the group that had the hand-holding, the deep intervention. But here's the part of the pointer study that I want people to Google it, find it, point-o-studder study, JAMA, you'll find it.

Starting point is 00:45:50 is that the group that got the program and didn't really get the guidance had a fairly dramatic improvement in cognitive function as well, not the extent of the other group, but nonetheless an improvement when they should have declined. Wow. That's how I answer your question about, is it too late? Is it reversible? And what can we do?

Starting point is 00:46:13 You know, it's about doing these things, though, earlier, get these things involved earlier in someone's life, so it's not as challenging. You know I'm all about optimizing performance, and lately I've been using the ion weighted vest during my workouts, and it's been a game changer. It isn't your average weighted vest. It's designed to fit like a second skin, activating your core, improving blood flow, and even helping you with recovery while you train. What I love most is that the weight is perfectly distributed. It doesn't pull on your shoulders or throw off your alignment, whether I'm doing strength training or cardio, or just taking a walk.

Starting point is 00:46:48 I'm burning more calories, building muscle, and putting muscle. pushing my endurance even further. If you're serious about leveling up your training and unlocking your full potential, check out the ion weighted vest at iongear.com. That's a-I-O-N-Gear.com. And you can use code Ultimate for 10% off and start training smarter today. Now let's get back to the Ultimate Human podcast. So just being more specific, what were the dietary interventions? I assume removing highly processed foods, lowering the glycemic impact of high-glycemia. sugars. Yeah. And it, we'll talk about that. Was there a keto reset? Something like that?

Starting point is 00:47:25 No. No. But again, back to to Benjamin Franklin. It is a question of, well done is better than well said. Right. Or well said, well said, well said is not as good as well done. You got to do it. Right. And again, you know, as Kennedy said, the time to fix the roof is when the sun is shining. And that's what we really want to target. It can be done later on as I just demonstrated. So So the diet in the interventional trial from Rudolph Tansy and Dean Ornish was very much a plant-forward, plant-centric diet. Okay. That's been Dr. Ornish's push for cardiovascular disease or cardiometabolic disease for an awful long time. I use the term cardiometabolic because metabolism affects the heart.

Starting point is 00:48:14 Well, metabolism affects everything. So we'll say neurometabolic disease as well. That's what Alzheimer's is. It's maybe the first time I've ever said that term, neuromatomatic disease. Yeah. I think it is, but let's make that stick. Yeah, let's make that stick.

Starting point is 00:48:29 I don't even think I put it in here today. Yeah, you saw it first. That's true. Can you guys get me neuromatabolic URL.com? No, I'm kidding. Neuromatabolic URL. com. But, you know, the point is that these are all ultimately metabolic issues

Starting point is 00:48:45 and through the intermediary of immunity, now immunometabolism, disease manifests. Cardiovascular disease is primarily an immune-related issue. What's narrowing the coronary arteries is an immune response. When you take the plaque out of a carotid artery or a coronary artery, it's loaded with immune cells. So it's an immune response, very much so,

Starting point is 00:49:08 directed by free radical mediated stress and inflammation. So to get back to, where we were, that these lifestyle interventions are by mainstream standards, not really embraced and often derogated. But when we look at the peer-reviewed literature, it's incredibly supportive. In the world of neurology, this is our only answer right now. Am I going to keep the door open and welcome an Alzheimer's drug if it does two things? It's fairly safe and it does the job. It's fairly safe, and it does the job. Absolutely.

Starting point is 00:49:48 I am so down for that. I will embrace that with open arms. We don't have anything like that right now, despite the TV commercials to the general population and despite the ads that are appearing in my neurology journal as a neurologist that I should be recommending these drugs that target beta amyloid. I went into it in great depth in this book.

Starting point is 00:50:11 Again, coming from somebody who would absolutely 100% be so down for these drugs. I'm all for making the toolkit bigger. But fundamentally we have to practice under two principles. Number one, primum non-no-sayer, above all, do no harm. Yes. And number two, looking at the risk benefit ratio. These drugs that are being used have dramatic risk and the benefit is nil. A Cochrane analysis was published about three months ago. The gold standard, you would agree in looking at trying to answer a question. The question that was asked, are these drugs doing anything? Right. And here's the answer. They looked at 20,342 individuals who are in 17 different studies, each study lasting 18 months of the current round of amyloid digesting

Starting point is 00:51:08 proteins, if you will, or monocle antibodies that take beta amyloid out of the brain, as a treatment for Alzheimer's, what did they find? Risk. 25% of people getting these IV drugs to rid their brains of beta amyloid had brain hemorrhages, brain swelling, or died. Wow. That's what. 25%?

Starting point is 00:51:31 25, 1 in 4. Wow. Number two, okay, that's the risk. I'm not making this up. I wish I were making this up that people could write comments about, oh, Gary Breck had this case, this guest, whatever. making it up, I wish I were, because then we could challenge veracity. Challenge my veracity. What's the benefit? The conclusion was basically none. The word used in the Cochrane

Starting point is 00:51:57 analysis was the benefits were trivial. Now, I say that and present this information in juxtaposition to the study that I quoted to you from Dr. Rudolph Tansy at Harvard, where they changed the lifestyle and the downsides or the side effects were that people's blood sugars came down, they lost weight, they felt better, and that was the other things that happened. Right. And these are existing Alzheimer's patients. Back to the pointer study that helps clarify one other point that you asked, these are the metabolically compromised 65-year-olds who had a,

Starting point is 00:52:39 two-year intervention of lifestyle plus brain training, I want to make it clear that a significant number of these individuals carried the APOE-4 risk marker for Alzheimer's predisposed. And what does that gene, what is the line that predisposes you to Alzheimer's? What does that gene do or not do that predisposes you to? I didn't write you that question ahead of time. Yeah. I should have though because it's a great question. Fundamentally, it threatens the microgleal cells.

Starting point is 00:53:15 That's what it does. Fundamentally, and more so in women, men and men. So at least you are more likely because of this gene snip to have microgleel cells who shift their metabolism and become villainous rather than become helpless. That's right. And again, to use your words earlier, it's a predisposition. It's not a genetic determinant. Yeah. It's the epigenetic factors that clearly are emerging.

Starting point is 00:53:39 Yes, it is. So you need to ratchet it up. If you have been told you carry the APOE for allele, then by all means pay heed to what we're saying today because it doesn't have to manifest at all. And, you know, it's interesting because it kind of gets us back to the beta amyloid hypothesis, which is only a hypothesis, which I think made people believe that that is,

Starting point is 00:54:06 is the cause of Alzheimer's, get rid of the beta amyloid problem solved. It didn't work. Still isn't working. Right. But, you know, to be fair, there are plenty of people who have been demonstrated to have high levels of beta emloid in their brains and are cognitively intact. Thank you very much. I was just reading that.

Starting point is 00:54:22 And others who have no significant amounts of beta amyloid and are going down the tubes with respect to Alzheimer's as a diagnosis. So that is, by all means, not the story. and we need to move ahead and really abandon this hypothesis. And where the research is now and where it's going in the future is targeting the microglial cells. I mean, you know, some very high-level work is being done to create monoclonal antibodies.

Starting point is 00:54:54 There's a study at Brigham and Williams using a particular monoclonal antibodies. This is a very high level science that's given now intranasally that helps keep the microglia in their M2 supportive configuration. They're exploring that in multiple sclerosis and in brain trauma. I describe it in the book. There are ways of targeting the mitochondria.

Starting point is 00:55:19 Think back to our conversation that a major characterization of the shift from being supportive to being destructive is a loss of mitochondrial function. There's a product that's called R&S. 60 that definitely targets mitochondria. It's a proprietary way that saline solution is hyper-oxygenated, creating these nanobbles of oxygen that seemingly mitochondria love. There's a future there. Even the drug metformin has a mitochondrial play.

Starting point is 00:55:52 Not just from its glucophage. It is glucophage. But there's much more than simply the activation of the AMP-Kynus that it looks like metformin glucophage is doing. So there's a lot of interest. You know, we will watch very closely the arms of the tame trial once that is completed to look at what people taking metformin are gaining, if they're gaining anything, anything they will, based upon this way of targeting their mitochondria. But guess what? You've got incredibly powerful tools for targeting your mitochondria right now. And it's more of a ketogenic diet and exercise. That's one of the most powerful ways of targeting your epigenome, targeting your epigenetics, but also targeting mitochondria. So even if they're a little deconditioned, getting them to do,

Starting point is 00:56:45 you know, like my mother can't go out and get into zone two cardio run in a 5K. But she can walk to the mailbox. She can definitely walk to know. Tomorrow she can do that twice. Yeah. That she could definitely do. And she could do resistance train. She's very strong. Your mother may surprise you. Yeah. You may surprise you. I could imagine in a couple of years as her cognitive function improves, that you might be well surprised at what she's able to do physically. Wow. So the exercise, obviously the glycemic diet, the omega breeze, I think it's also important that we touch on the importance of sleep in the lymphatic system and what's happening with the lymphatic system during deep phases of sleep

Starting point is 00:57:25 and how important getting proper sleep and how detrimental sleep deprivation, at least over a prolonged period of time, short bouts, you know, travel or what have you. What can I say? It's huge. It is, it's huge. Sleep, eat, and exercise. Yeah. What was it? Eat prey and love. important as well. But yeah, and sleep might be clearly the most important of all three. Diet's not great. Exercise not often.

Starting point is 00:58:01 You don't sleep, well, you're done. You are finished. Even if you don't sleep for a few days, you won't survive. Yeah. You can fast for, I mean, you know, people fast. 30 days. Oh, yeah. Yeah. So we have that ability.

Starting point is 00:58:17 No, sleep deprivation is the old. one of the oldest forms of torture. I mean, that's right. That's, you know, your brain just degenerates very quickly. Mechanistically, what's happening? You mentioned the glymphatic system. We can unpack that, certainly. I love to.

Starting point is 00:58:31 But sleep is hugely influential in terms of inflammation, in terms of insulin functionality, and overall metabolic regulation. Those are the keys to the kingdom in terms of regulating your microglyle cells, keeping them supportive or allowing them to become destructive. That's the keys to the kingdom right there. So even one night's non-restortive sleep

Starting point is 00:58:58 dramatically affects insulin functionality, is manifested by elevation of your blood sugar compared to the baseline, ramps up the production of these inflammatory cytokines that your microglia will see, tend to shift them to the dark side, as it were, and generally is to be, avoided. It happens. Even cognitively that very next day, you're having issues.

Starting point is 00:59:21 Yes, we all know. Interesting, a study came out this year that show that to some degree, some of the cognitive dysfunction that you have after one night of not sleeping or not sleeping enough or well enough is offset by caffeine. I mean, well, we all inherently knew that. Yeah, yeah. Best practice here. But this actually looked at what's going on and on, on, cognitive testing, and I think it involved a fMRI evaluation as well. So, you know, underrated, you spend eight hours you should, or they're about sleeping. That's a third of your life. Yeah. Though you were spending more as an infant and a toddler, but a third of your adult life should be spent doing this. You're not going to sleep, you're not going to eat for eight hours

Starting point is 01:00:07 or exercise for eight hours. Right. I guess some people might, but a third of your life, allowing your brain to contextualize your experience, to build new memories, and to via activation of the glymphatic system, help offload the debris that is accumulated, the misfolding of the proteins, the glycated proteins, the proteins that abound inappropriately to blood sugar, and the bacterial breakdown products that your brain does, in fact, accumulate. And where do you fall on creatine supplementation in older adults, or specifically those with cognitive decline because we touched on it briefly, but do you have any opinions on the form of creatine, monohydrate versus hydrochloride? Have you read the studies where it can

Starting point is 01:00:54 mitigate the effects of sleep deprivation? And certainly in some cases, some wild claims about I'm going to see, reversing Alzheimer's, but treating Alzheimer's. Well, let me just start with that. The study was extremely small and it was an interventional trial. Like an end of two or something. I think it was five. Five, okay. But it was a very small trial. And frankly, there were some cognitive improvements in these individuals. I mean, we need a big trial of creatine as it relates to Alzheimer's.

Starting point is 01:01:26 And what they did demonstrate that I think was really quite remarkable was they were able to image creatine levels in the brains and, in fact, demonstrate that they'd increase. So we've got a way to go, ways to go. But I would say that mechanistically, as we understand, what creatine is able to do. It makes sense. I recommend it. It's one of my key supplements in this book. And is it early for me to be bullish on creatine?

Starting point is 01:01:52 Yep, it is. And I'm fully happy to admit that. Do I take it every single day? You bet I do. How much do you take? I take about seven grams of creatine monohydrate. I'm seeing the data on better GI tolerance and absorbability of creatine monohydrate, but I'm not compelled by it.

Starting point is 01:02:09 You mean hydrochlorate? Hydrochlorine, yeah. That's correct. And so I'm not compelled by the idea that hydrocloid is necessarily dramatically better. We'll watch. More soluble, I think. Yeah, yeah, and we'll watch that.

Starting point is 01:02:21 But creatine monohydrate is widely available. It's really inexpensive. It's tasteless. Yeah, you can have GI upset if you overdue when you first start in. No question. But if it doesn't enhance mitochondrial function in the brain, which is what we're hoping for,

Starting point is 01:02:37 but does allow you to perhaps build a little bit more muscle mass, and enhance mitochondrial activity in the muscles, that's good enough for me. Right. Based upon our earlier conversation of the relationship between muscle mass and muscle activity and functionality,

Starting point is 01:02:54 ultimately on the brain, through the formation of these myokines that are good for the brain and good for metabolism, then I am all in. The story is unfolding. I wanted the readers to be, go ahead and start your creatine

Starting point is 01:03:08 with, disclaimer, or your healthcare overseeing all of this, as if, while hoping that your healthcare provider has sort of creatine, we'll leave it at that. But I don't think we're too early. Risk, I don't see much risk. I mean, there's been a discussion about people with existing kidney disease to check with your healthcare provider

Starting point is 01:03:30 on the front end. And I think there's an argument that when you take creatine and you raise your levels, it's metabolic downstream manifestation is the formation of something called creatine. So they're sounding similar, but they're very different. So your creatinine level actually may go up as you take creatine. Why is that relevant to this discussion of the kidney issue?

Starting point is 01:03:55 Because when your creatinine level climbs, then your doctor might say, gee, that's an indication of kidney damage and your kidney function is declining. Well, realistically, it's rising because you're taking. a supplement that is metabolized into creatinine. So yeah, it's worth looking at the B-1. I've seen that in you do blood draws on athletes

Starting point is 01:04:19 that have just done a heavy squat workout. Yeah. They look like they're in kidney failure. Based on the blood work. Based on the blood work is what I mean. You know, because they're creatinins off the chart. And- Exactly. Eight hours later, it's normalized. I mean, there are other ways of assessing kidney function.

Starting point is 01:04:33 Let's look at the BUN. EGFR. Let's look at the estimated glomerary filtration rate. you're correct. But to suddenly say, no, stop creatine, look, your creatine went up. To be fair, I mean, maybe somebody is having renal issues for that reason or other reasons.

Starting point is 01:04:50 I'm not saying just because you started creatine that you should ignore your other blood work, but that's what we need to think about. So let me just, you know, recognize that creatine in and of itself is perhaps not necessarily the mitochondrial tonic that I think it's made out to be. What creatine does is in the presence of an enzyme phosphocreatine,

Starting point is 01:05:20 or rather creatine phosphokinase, that creatine binds to phosphorus, holds on to that, rather, binds to, creates a phosphate binding to creatine, forming phosphocreatine that then serves as a reservoir for that phosphate group to then participate. to then participate in the formation of ATP when it's needed. So there's this right in my next door,

Starting point is 01:05:46 neighbor's house is a great source for me to make energy. That's what phosphocene is. Well, it's right in the garage in my ATP producer. So, you know, it's a resource for better ATP production. So in that regard, that's how it works. Hey, guys, let me tell you about one of my favorite new hydration drinks. Now, this is for distance athletes, hits cardio exercises, people that sweat a lot or exercise intensely.

Starting point is 01:06:12 An A game is a hydration drink. It has eight essential vitamins. It has all of the electrolytes, the entire suite of B vitamins. Before you freak out and read that it has 21 grams of sugar, which it does, the sugar is coming from natural cane sugar and honey. My preferred mechanisms for getting glucose into the blood during intense exercise. It also has natural flavors, but these natural flavors don't come from bacterial fermentation. They actually come from real citrus fruits. and the color is from vegetable juice, not artificial dyes.

Starting point is 01:06:40 So next time you're looking for a great hydration drink and you're exercising intensely, a game is your choice. Now let's get back to the Ultimate Human podcast. In the book, do you talk about any other must-have supplements or supplements that look promising for brain support? I mean, I think this whole wave of neurotropics and brain health supplements, you know,

Starting point is 01:07:05 see they're becoming extremely popular. I wonder if you have an opinion on any of those or if you, are there any that are must haves in your book or any that you're excited about that are on the horizon for neurocognitive decline of all sorts. And it specifically may be related to the microglueal cells. Yeah. I will put a huge vote in for vitamin D. Who knew? It might be one of the cheapest supplements out there these days. Colicosephral. Yeah. Yeah.

Starting point is 01:07:39 And why? It's the only vitamin that human beings make on our own. So you've got to think, wow, if we don't need to eat, drink, or breathe to make vitamin D, you know, we just eat some cholesterol and some sunlight. Calestral. I'm over simplifying. No, that's pretty simplified. You know, that's basically what you need.

Starting point is 01:07:57 You know, then it has to be pretty important to human function because we don't even need to get it from diet. But we're our vitamin D receptors on microglial cells. Let's start there. That's wild. And I'll backtrack a little bit because these days people are understanding their genetic profiles and learning that they may have polymorphisms or variations in their vitamin D receptors. So for all of you who get your genetic material printouts, look for changes in the VDR information, vitamin D receptors, and they'll give you whichever program you're on,

Starting point is 01:08:39 whether it's 3x4 or whatever genome profile sequencing company you're working with, they'll tell you you have a VDR polymorphism, and you might need to consider a higher dosage of vitamin D. Or, as you well said, perhaps get a little bit more sunlight. Sunlight is a pretty effective way. But we wear clothes generally outside. Most of us do. Some of us don't.

Starting point is 01:09:02 Or some people don't. But that said, I don't want to say that everyone should take vitamin D as a supplement out of hand. Get your blood level checked. If you're already between 60 and 80 on your levels, then by all means, you're doing great. Whatever you're doing seems to be working. Maybe you're getting your vitamin D from sunlight, from food, from your multivitamin or wherever. But if it's not, and I'm talking now to most of your, maybe not your audience, but most of the general population. Yeah, more than 50%.

Starting point is 01:09:33 Yeah, your vitamin D is not, though it may be considered borderline normal range, it's not optimized. 30 is normal. 30 doesn't work for me. No, me either. So 60 to 80, closer to 80, mine is about just under 80.

Starting point is 01:09:49 And that's where you want it. So that helps keep your microglial cells on your side. That's what you want. So I've been saying that for a number of years. Let's talk about a couple of interesting studies that just came out. one study that came out this year in the context of a different study

Starting point is 01:10:06 which just floated my boat. I was talking to my best friend chat GPT the other day at the gym. Chats a good friend of mine too. And we unpack this study. I have it the best time. I want to hold chat chabit to the mat on going deep on these ideas.

Starting point is 01:10:21 So here's what the study talked about. That they took a group of people in their 30s and several thousand people they followed them for 16 years. At the beginning of that, 16-year prospective analysis, they measured their vitamin D levels. At the 16-year point, they brain scanned them for tau-protein.

Starting point is 01:10:45 Now, your audience may or may not know what tau-protein's all about. I'll back up to the study just a minute. JAMA just published a study. We've known that this phosphor-related tau-217 is a way we can help diagnose Alzheimer's if we're not sure, predicts how quickly a patient will decline. But the new study in JAMA showed that this P-Tal 217, one of the fundamental blood tests I'd like everyone to get, is predictive of who's gonna get it.

Starting point is 01:11:17 Well in advance. Let's get back to the vitamin D study. So the vitamin D levels were looked at in juxtaposition to measuring Tau in the brains of people using a special scan. Higher vitamin D levels, lower tau in the brain. Wow.

Starting point is 01:11:35 Now, to be fair, that's a correlation. Right. Higher vitamin D, lower tau in the brain. Do I think that's important and therefore supports the idea that we should make sure our vitamin D levels are where they need to be? You bet I think that. Again, that's not what the study allows me to say from a science perspective, but my personal view, which is, I guess, what all of our views are, is that you bet you need to maximize

Starting point is 01:12:02 or optimize rather your vitamin D level. It's that important. It reduces inflammation. Vitamin D receptors on those microglue cells via make their way to the nucleus and transcribe genes that are doing good things. It makes their way to the mitochondria and it helps with energy production.

Starting point is 01:12:20 So I'm all in. Okay. So creatine, vitamin D, vitamin D3, anything else that is. Oh, well, there's lots. Well, we've got time. Third hour. We'll do the third hour.

Starting point is 01:12:32 And I'll bring this up because an interesting study published about two months ago challenged the wisdom that omega-3 supplements, fish oil in particular, was good for the brain. It was an interesting study that looked at records of individuals, whether or not they became demented, and cross-reference that, if you will, with whether they were taking fish oil or not, and concluded that fish oil was of no benefit in reducing risk of Alzheimer's, and in fact may have actually slightly increased risk. Oh, wow. Right.

Starting point is 01:13:07 Now, at first blush, a lot of the people watching us right now, your audience, saying, why, that's crazy. I mean, I've known for years that we should be taking DHA, fish oil, omega-3s in general, good for the brain, right? Right. It's been our messaging, and for me, it's still my messaging. Why was this study? in the face of all of the studies demonstrating correlations between higher levels of DHA in particular and

Starting point is 01:13:34 lower risk of becoming demented, dating back to the original work of Martha Claire Morris from Rush, why was this new study, in my opinion, off base and serves as a huge disservice to people? Well, reading the literature or getting informed these days, what's the first? thing somebody might reach for if there's developing dementia. Omega-3s. Right. Right. I mean, what would you tell somebody?

Starting point is 01:14:05 Oh, yeah. I'm, my friends are having, I have a particular friend who's having cognitive decline. What should he or she do? Well, omega-3 should certainly be part of that equation. So you're selecting people out now. Right. By putting them, by these people are going to gravitate to take, demented people or early dementia, subjective cognitive impairment,

Starting point is 01:14:24 are going to gravitate to the omega-3s. anyway, that's going to skew these results. You've already selected a group of people who may be experiencing cognitive decline, number one, number two. To be fair, there's a lot of crap on the shelves in the grocery store being sold as high quality fish oil in a clear plastic container that's been sitting there probably shipped in a hot truck or who knows what. How was it refined?

Starting point is 01:14:51 All the things that may not have the efficacy we're looking for. Likely it does not. So for those reasons, and our understanding of the chemistry of DHA, mentioned one thing that DHA does earlier in our time together today enhances the production of brain-derived neurotrophic factor. DHA is a cox 2 inhibitor, i.e., it's an inflammation reducer in the body. Therefore, we need DHA. It's a powerfully important structural component of the neuronal membrane where all the information

Starting point is 01:15:23 gets transmitted. It makes up part of the synapse where cells connect to neurons connect to each other and share information. So don't throw the baby out with the bathwater on this one. I couldn't agree with you more. I take an olive oil in the morning. I take phosphodidylcholine in the afternoons and I also take a fish oil. Right.

Starting point is 01:15:43 Yeah, I load up on the EPA, DHA. There are plenty of other things that are not expensive that we should be thinking about like B complex, a good B complex. Now, might you need a special form of B complex as I do? Because my homocysteine was slightly elevated. Homocysteine, an important lab study, a powerful risk marker for Alzheimer's. You get a homocysteine level now on the various labs that you're able to get bundled without a doctor's prescription. Homocyst is included. Why? Because it's a powerful risk marker for cardiovascular disease, and as such, because it's a risk factor for that, you would expect it to be a risk market for Alzheimer's, and indeed it is.

Starting point is 01:16:31 Wow. But here's the good news. You can drive homocysteine levels down with B-complex. B-complex and TMG. Yeah, trimethylacine. Trimethylacine. Or dimethylaclycine. Yeah.

Starting point is 01:16:43 Unless you have a genetic quirk, which I have called M-T-H-F-R. I mean to be too technical. But I will guarantee you some of your viewers know exactly what I've talked about. All of my viewers too. Right. MTFR. I've been standing on MTFR for 12 years. Methylene tetrahidropholyte reductase.

Starting point is 01:17:02 Yes. And that is a mouthful. Also called the motherfucker. Just say it. We'll leave it in the head. Just say it, David. You're gonna get me to do that now. You're gonna bleep it out anyway.

Starting point is 01:17:12 But, okay. So I think that, you know, this is fantastic information. Mm-hmm. hashtag WTF, why, that's fantastic. Yes. Right? That's what it stands for. That we now have the ability to not only say, well, your homocysteine is elevated, but here's why.

Starting point is 01:17:32 So for these MTH of our people, myself included, we know that we are at risk for elevated homocysteine and other issues by virtue of the fact that we don't methylate. And we can fix that by taking not just B complex vitamins, but they have to be methylated. Methyl folate, methyl B12. Problem solved. My homocyte went down to 6.8. I was 15. Now it's 7. So if you had a homocysteine of 15, that needed work.

Starting point is 01:18:01 And who knows how long in your life, you didn't know this. My whole life, well, 6 years, 8 years ago. Yeah. Yeah. I've supplemented ever since. And there are people that we will talk about, perhaps off camera, for whom we need to know their homocysteine levels and vitamin D levels and all the things. right now.

Starting point is 01:18:20 I mean, we talked about the microbiome and all that, all well and good. These other things are very powerful levers. Yeah. And will allow us to really make headway. First of all, I agree with everything you're saying, the methylated multivitemones, the methylfolate, methylcabalman version of B12.

Starting point is 01:18:36 Some genetic variants need the hydroxia or the adenicil. Yeah, it's not a big deal. It's super easy. You know, I look forward to my sublingual B12 because it's sweet, And it's the only, you know, it's my real treat. My subling will be 12. Sometimes I might even have two if I'm feeling like I'll reward myself.

Starting point is 01:18:56 Yeah. That's how lame I am. Eat so little sugar you mean. Oh, yeah, but I will have dark chocolate. Yeah. You know, I have 85% and that has very little sugar. And fruit, I eat and it's got sugar and I'm well aware of that. But, you know, fruit, honey and maple syrup are where I get my sweets from.

Starting point is 01:19:10 And then I use alulose. Alulose is, you've covered it. Yeah. It's magic and, yeah, until it isn't. but I think it's, for me, it's, I would agree with you. A very important player. As a, call it artificial sweeteners.

Starting point is 01:19:24 It's not actually an artificial sweetener, but it's, no, I don't want to call it an artificial sweetener. But it is manufactured. It is a sweet alternative. Yeah. And, because I don't want to throw it in there with aspartame and all that other nonsense. No. And, you know, I think that perhaps monk fruit's innocuous,

Starting point is 01:19:41 I, you know, I'm not a fan of the affidase of stevia. You cut it a lot with urethritazole, but the, Pure monk fruit. Yeah, I think the data relating higher levels of erythritol consumption to cardiovascular risk is real. I, you know, there, I read that study. And so, but, you know, if you're chewing erythritol sweet and gum, I can't think you're getting a huge dosage of erythritol. Right. But if this is compared to sugar, then you've made the right choice.

Starting point is 01:20:10 Right. So, oh, but it's natural. It's cane sugar. It's coconut sugar. It, call it what you will, it's sugar. It's sugar. And, oh, but it's organic and somebody, you know, put crystals over it, whatever. I don't care.

Starting point is 01:20:26 It's sugar. You got to stop. Right. And gosh, this Dr. Poldmutter is a pain in the ass, isn't he? Yeah. I mean, he's making, and the reason I am this pain in the ass is so that when you're my age, you'll be able to have, hopefully, what sounds like an intelligent conversation about intriguing topics, and you'll be able to satisfy your curiosity, remain curious, remain engaged,

Starting point is 01:20:48 You're doing your best to keep your physical body. And remain independent. You know, that's- And remain what? Independent. Independent. That's the thing that I, you know, my heart bleeds so much for my parents is they're losing independence.

Starting point is 01:21:01 Losing agency. Yeah, and losing agency. And, you know, and that to me is, you know, the definition of, you know, your life's decline. I mean, most of us, I think if we had the choice of lifespan or health span would say, I want to the longest life's fan with the longest health span. But as my health span starts to go off a cliff, you know, there's not a whole lot of joy you derive out of life. Yeah. And, you know, the worst situation is people who remain kind of physically in fairly good stead, but cognitively decline. Yeah. And it's just tragic. Yeah. So, first of all, I agree with and love everything you've said

Starting point is 01:21:43 so far. Uh-oh. Yeah. I do. I mean, I'm in the medley-old. So I got a good score going into the You've got a good score. I mean. Double point questions are coming soon. Great score. The bonus questions. So any other supplements, and then I want to shift to some modalities. I actually want to get your opinion right out in the open on some of the things I'm doing for my mom,

Starting point is 01:22:02 which include transcranial red light, which is saturating her brain with red light, certain wavelengths of red light, known to be therapeutic, specifically the ones that dissociate mitochondrial nitric oxide from cytocrineal dioxide from cytokromsiaoxy. to force oxygen, for lack of better words, into the mitochondria to change this metabolic cycle of the mitochondria. I wrote about them. You did? Oh, it's red lights in the book.

Starting point is 01:22:30 Okay, great. But, you know, it may seem hokey. It isn't. We are, you know, we see what it's doing in laboratory animals, that it is able to penetrate into the brain, that it is powerfully effective in terms of what you just mentioned. just mentioned, reducing inflammation, which from a microglial perspective is a home run.

Starting point is 01:22:51 Right. And, uh, and, and, and directly targeting the mitochondria. It's, it's hard mitochondrial therapy. Target them, right? Um, you know, to just select the mitochondria, because there's a, a long distance between, let's say, oral supplementation,

Starting point is 01:23:09 and getting through the mitochondria and getting into one of those stages of the Krebs cycle, electronic transport chain, and, and light, can do that. I mean, it ignores the cell wall, nor is the mitochondrial membrane, and goes into certain complexes and actually exerts a measurable effect.

Starting point is 01:23:26 Well, that's what the beauty of, one of the things I mentioned earlier, this RNS-60, instantly just transgresses, makes it away into myocondria. What was the RNS-60? So RNS-S-60 is a nanoparticle change of saline, normal saline,

Starting point is 01:23:45 make hyper oxygenating normal saline. Clinical trials so far in ALS, extending life by six months, but dramatically preserving respiratory function and speech, pretty significant, I'd say. And cutting a hospitalization time in half in individuals who've experienced a stroke. Wow.

Starting point is 01:24:08 Yeah. And where do you get this? Well, this is experimental. Oh, it's going through trial. No, well, it's being. used for developed for scientific research, though that may change. One would hope. Can you get a hold of it now?

Starting point is 01:24:23 No, no. It, I... You have it, though. Oh my God. Busted. Busted. All right, we'll talk after the podcast. But having said that, the company is called Revelascio, Revelaceo.

Starting point is 01:24:41 Revellasio. And their science is just... so forward thinking. Yeah, very, very exciting. Hyper-oxygenating saline. So just trying to think of the mechanism there. Interesting. Yeah.

Starting point is 01:24:56 But, I mean, there are protocols now being done in humans to transplant healthy mitochondria into humans. The first studies were in children who have had required heart surgery and couldn't come off what's called the ECBO pump. oxygenation bump afterwards, by transplanting mitochondria into their hearts have had a dramatic increased ability to come off of ECMO and survive. Where do they get the mitochondria? Well, they're taken from the leg muscle, actually. So you relocate mitochondria from functional areas of the body to spin them down and then into the body. Can you imagine? The idea of transplanting mitochondria

Starting point is 01:25:38 into the brain? I mean, you know, we're scratching her head right and I think, oh my gosh, could that ever happen. Look what's happening right now. Right through the Cripoform plate or some kind of intranasal. Through the Crippiform perhaps, but I would think first it'll be injected into the ventricles, into the spinal fluid itself. But there are, but using the Cripoform for this monoclonal antibody, this for Alamab that's being developed at Brigham and Williams. Brigham and Williams.

Starting point is 01:26:08 It's small enough to pass her. Oh, it's a monoclon antibody. It makes its way right through, yeah. There's a lot of things being delivered via this nasal end, even exosomes now. But that said, even microglia, healthy microglia, are being created from stem cells and through CRISPR intervention, become microglia, the M2 supportive microglia. And already a human trial has been undertaken for not, it's a different ALS, not the one you're familiar with. called ALSD, which is almost uniformly a fatal condition and basically has arrested the disease

Starting point is 01:26:48 by giving them healthy, good functioning mitochondria. It has been defined as a defect of microglial function. By giving them healthy microglia. I mean, make sure, I think I said mitochondria. Yeah, likely. By giving them healthy microglial cells into their brains, basically saving these people's lives. Wow.

Starting point is 01:27:09 Pretty astounding. And again, where are they getting the microglial? glial cells. These are created from stem cells basically. Wow. That is so fascinating. I'm a big fan of exosomes, especially because of their particle size,

Starting point is 01:27:22 about it, 1,800, the size of a stem cell. Recently, a study was published where exosomes were created from human cells that were like microglial cells, but just a little bit earlier in their development. From these human cells, exosomes created, administered, intranasally to the laboratory mouse model of Alzheimer's disease and having really a profound

Starting point is 01:27:48 effect on reducing beta amyloid lobe. We talked about why that may or may not be critical, but also improving their cognitive function, preserving their cognitive function by giving them intranasal exosomes derived from human like human like microglial cells. So your position clearly is Alzheimer's is something that is high. highly preventable, given the right lifestyle factors, and may have some very, very promising treatment alternatives to what's out there right now. Yeah, and that's right. And I look at what the near horizon looks like and the far horizon, for that matter,

Starting point is 01:28:29 in terms of what people are looking at through the lens of these microglial cells to bring about improvement, bring about, I would hope for a cure of this situation. And again, it's not just that your guest today is saying that lifestyle issues can reduce the risk of this happening. This was published in the journal The Lancet in 2024. The Lancet Commission indicated that if we could pay attention to 14 modifiable factors, that the incidence of dementia could be reduced by as much as 50%. Wow. It was an interesting...

Starting point is 01:29:08 And I assume that is a... applicable to Alzheimer's too. Oh yeah, well, Alzheimer's is the most common cause of dementia, by far and away. It was interesting, though, and I've said this before, and I, that they didn't mention diet. So I, along with the guy, Dr. Robert Lustig, where we wrote this letter to the editor to the Lancet and said, hey, here are the multiple studies talking about the various diets, whether it's Mediterranean, Mediterranean, Plus, the mind diet, you name it, and how they play out in terms of dementia risk. So we're sure this is just an oversight and we got a pat on the back and said,

Starting point is 01:29:46 we're not going to publish your letter to the editor. Ah, wow. Okay. Well, there's a lot of, uh, why, you know, forced to be out there. Yeah. Yeah. Don't want us to think that food is medicine. Yes.

Starting point is 01:30:00 And let me say that we've talked about the broad strokes. I'm happy if that's the only, message that lands because it's huge. Exercise diet, sleep, being in the presence of other people. Not often talked about is a huge issue, but when you go back to the blue zones, those who live the long-

Starting point is 01:30:20 Isolations. And the healthiest, isolation is a major risk for developing Alzheimer's disease. Don't be isolated. And if your elders are isolated, do what you can to make that not happen anymore. I could not agree with.

Starting point is 01:30:34 Even if it's virtual. Even if it's virtual. Even if they have a pet. Looking into the eyes of a dog has powerful effects on your microgle cells. Wow. Think about it. That's why I was greed when I walked in here by your dog. Yeah.

Starting point is 01:30:51 And I felt, yeah, you're catering to my microglial cells. I got hosed in that one. I lost that battle. My youngest daughter convinced me that we were sheltering. Like we were fostering. That was the term she used. We got it from the shelter to, we were gonna foster it for like two weeks.

Starting point is 01:31:09 And then it never works. It was gonna go to another home. That never works at all. Okay, that's been what, six, seven months now, eight months, I think. No, I'm glad to see that you have a dog. It's, yeah, that's great. He's here now permanently. You know, we've seen that baby.

Starting point is 01:31:21 He's a great dog. Oh yeah. Looks like a pit pole, so he looks very scary, but he's just a tiny, he looks great. He jumped up on me out. I thought was great. Lick me him. Yeah, yeah.

Starting point is 01:31:31 That's all good. He's a teddy bear. You know, So how does it work? Well, we could talk about lack of social engagement, isolation, amps up cortisol. Cortisol is immediately and directly threatening to the health and mitochondrial function, I might add, in the hippocampus, the brain's memory center. It's so fascinating. When we were in the, this is going back years, but in the mortality space, we knew that isolation had a dramatic,

Starting point is 01:32:02 dramatic, there's a lot of data around this, by the way. Oh, yeah. A dramatic effect on lifespan. I mean, we know about broken heart syndrome, right? I mean, you show me a couple married 40, 50, 60 years. One passes away. The other one usually goes very quickly. And when we had these second to die policies or permanent universal life policies,

Starting point is 01:32:21 we had a lot of data on isolation. And it accelerated all-cause mortality. And you know what else? anecdotally when you think some of the most horrific crimes you know when you read the paper and you're like who was that committed by? Oh, that was a kid that never talked to anybody that's the most isolated. Never came out of his room.

Starting point is 01:32:41 He always kept a clean room. Has you ever noticed that? Yeah. So they interview somebody, you know? Yeah. So the isolation is a major factor. And you're right, the Blue Zones community connection,

Starting point is 01:32:57 prayer. Yeah, I mean, that's what Dan Butener called out. It's not a pill. It's not a specific dietary recommendation. Yes, these people felt engaged in their communities. And it's huge. They also felt a purpose, you know, like, exactly.

Starting point is 01:33:14 Why am I here? You know, when an elderly person is just sitting around alone all day for days on end, you know, my grandmother's sister was like this, you know, they're just alone with that. their own thoughts. And, you know, they got to think, why am I here? We could talk about mechanistically what may be going on. Well, we know that that's a stressful situation.

Starting point is 01:33:41 Cortisol levels go up, as I mentioned a moment ago, threatening directly to the hippocampus. Dr. Robert Sapolsky talked about that 25 years ago in primates who constantly were under threat, looked at their hippocampus after post-mortem and they were shrunken. Yeah, that's memory. But beyond that, what's the upside here of engagement? What happens when you're with people and looking them eye to eye as you are right now? My oxytocin level, my love hormone is going up. And oxytocin is bound to the supportive microgle cell and tells them,

Starting point is 01:34:15 you better just stay in this M2 configuration and be a brain defender. So you right now are keeping my microgle cells, along with your dog, in their supportive role because we are in a situation where we're feeling good about each other. We're having feelings of love and because we're doing good things. And so, you know, if you have to break it down to a mechanism, okay, there are some mechanisms,

Starting point is 01:34:40 but we just inherently know that to be true. Yeah. If you ever watch alone, you watch a TV show alone, I've seen times when, my gosh, there's a contestant and it's who can last the longest on their own. I mean, these people build

Starting point is 01:34:57 musical instruments, a canoe, a house, you know, a hot tub, all these things they're building, this guy's going to win. Home run. He's great, you know, and the next, you know, he says, look at all this stuff I've built. I can't take it anymore. Yeah. He pushes, he calls them the next thing, they pick them up. Yeah.

Starting point is 01:35:16 Because it's just very, very stressful to be alone. Yeah. And, again, it can be virtual, but we've got to keep people in the loop. Yeah. Love it. Dr. Perameter, this is amazing. My VIPs are waiting with a whole list of questions for you because I told them that you were coming on the podcast,

Starting point is 01:35:38 so we're going to head over there to the VIP group. But before we do, I end all my podcasts by asking my guests the same question. And that is, and this can be an interesting answer coming from you. What does it mean to you to be an ultimate human? To be an ultimate human means to identify your skill set, and exploit it to its fullest. Wow. That's probably another way of saying fulfill your purpose.

Starting point is 01:36:04 Exactly. Right? Skill set. Identify it and fulfill it. Identify it and fulfill it. That is one of the most succinct answers I think we've ever gone. Well, I think that everybody has something. Yeah.

Starting point is 01:36:14 Well, this has been a great pleasure for me. Me too. Really, 2014 was a game changer for me when I read your book. It really had a long-lasting, impactful, impact on my career and was part of... I'm very, very honored and happy to hear that. Yeah, thank you. Yeah, it really did.

Starting point is 01:36:33 And I'm looking forward to reading this book because it also is very appropriate for the position that I'm in with my loved ones, and I'm going to share that on my platform. But thank you so much for coming on the ultimate podcast today. We've got lots more work to do. Oh, no, no, I'm going to have you back. I mean, especially as I get through this book,

Starting point is 01:36:52 I'm going to have a whole other podcast. podcast full of question. Yeah, sure. And until next time, guys, that's just science.

The Ultimate Human with Gary Brecka - 306. The Alzheimer's Drug With a 25% Brain Bleed Risk - Dr. David Perlmutter

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