Dhru Purohit Show - Why Blood Sugar Regulation is a Key Part of Alzheimer’s Prevention

Episode Date: February 3, 2025

This episode is brought to you by Cozy Earth and Pique Life. We know the seeds of Alzheimer’s are planted at least twenty years before a diagnosis. So, it’s never too early to make crucial lifestyle changes that can influence brain health and the risk of developing neurodegenerative diseases.  Today on The Dhru Purohit Show, we’re bringing you a special compilation episode featuring Dhru’s conversations with leading experts on Alzheimer’s and brain health.  Dr. David Perlmutter explores the key factors that influence Alzheimer’s risk and shares his top lifestyle strategies for prevention. He also discusses tools to assess brain energy usage and dives into the gut-brain connection. Dr. Mosconi explains what happens to a woman’s brain during menopause and its connection to Alzheimer’s disease. She also shares how recent research validates women's experiences in perimenopause and menopause, along with key lifestyle habits to prevent dementia and support a smoother transition. Dr. Perlmutter is a board-certified neurologist and five-time New York Times bestselling author. He is a fellow of the American College of Nutrition and serves on their Board of Directors. He has published extensively in peer-reviewed scientific journals, including the Journal of Alzheimer’s Disease, Archives of Neurology, and Neurosurgery. Lisa Mosconi, PhD, is an associate professor of neuroscience in neurology and radiology at Weill Cornell Medicine and the director of the Women’s Brain Initiative and the Alzheimer’s Prevention Clinic at Weill Cornell Medicine/NewYork-Presbyterian Hospital. She is the New York Times bestselling author of The XX Brain and Brain Food. In this episode, Dhru and his guests dive into: Genetics vs. Lifestyle: Their roles in diagnosis and impact on health (1:39) How Insulin Resistance Affects the Brain: Compromised brain energetics (04:20) Key ingredients that impact the body like sugar  (11:11) Blood Sugar Game-Changers: Strategies for better management (20:14) Foods Dr. Perlmutter avoids & the gut-brain connection (27:32) The brain’s energy demands & top antioxidant-rich foods (34:32) What’s happening in the brain during menopause (38:31) Validating menopause symptoms and women’s experiences (47:32) Brain changes in perimenopause & key transitions (52:02) Why the brain is unique and why consistency is key (59:32) Also mentioned: Full episode with David Perlmutter Full episode with Dr. Lisa Mosconi This episode is brought to you by Cozy Earth and Pique Life. Right now, get 40% off your Cozy Earth sheets. Just head over to cozyearth.com/dhru and use code DHRUP. Right now, Pique Life is offering 20% off the Pu’er fermented black and green teas. Plus, you’ll get a free beaker and frother when you go to piquelife.com/dhru. Learn more about your ad choices. Visit megaphone.fm/adchoices

Hi everyone, Drew Prode here. Let me share some pretty sobering statistics with you. Globally, 55 million people have been diagnosed with Alzheimer's disease, and that number is set to triple by 2050. But you might be surprised to learn that only 3 to 5% of those cases of Alzheimer's disease are driven by only genetics. The truth is that Alzheimer's disease and all cognitive decline has largely been shown in surveys all around the world to be seen as one of the scariest things that anyone could imagine happening to themselves. And I've seen this firsthand and the devastating impact that this can have on

individuals and families with my own grandfather, who I took care of while he was going through his own Alzheimer's diagnosis. But we know now that there is so much more that can be done to support our brain health as well as reduce our risk of developing Alzheimer's disease and dementia. And in today's compilation episode, I'm talking with board-certified neurologist and best-selling author, Dr. David Perlmutter, about the crucial role of blood sugar regulation in preventing Alzheimer's disease. I'm also speaking with Dr. Lisa Mascone, an associate professor of neuroscience in neurology and radiology at Cornell Medicine, and the director of the Women's Brain Initiative, and the Alzheimer's Prevention Clinic at New York Presbyterian Hospital.

Dr. Mascone and I talk about the impact of glucose metabolism. on brain health, particularly in menopause. But first, let's dive into my conversation with Dr. David Perlmutter. Give us the next big bucket that you often see for people that often doesn't get as much attention as diet does when it comes to cognitive decline, dementia, and Alzheimer's. I'd say that first, as a counter to the notion of, you know, what are the big legs that support this decline would be genetics. Genetics is not that relevant. In fact, playing only about 5% role that people say, well, I carry the APOE4 allele, therefore I'm at greater risk. But understand that

that's so-called Alzheimer's gene plays upon other variables that we can absolutely control. So, you know, the point I want to make for your viewers is really quite simple. And that is if mom or dad had Alzheimer's, or if you know that you, by virtue of your 23 and me or other genetic profile, carry one or two of what are called the APOE4 alleles, which are indeed associated with increased risk for Alzheimer's, all well and good and interesting. No question that having that genetic predisposition and others, pre-sendulin-1, for example, increase your risk, but by all means the die isn't cast. It means that our choices, we have control over things that are really influential. And I think the biggest issue would be, and they're all important, don't get me wrong, but I think

the biggest issue, at least in our modern world, has to do with our metabolism and elevation of our blood sugar and therefore compromise of our ability to have insulin in the body do its job. And I think, you know, to take a step back, back to high school biology, well, what's the importance of insulin? Insulin is important for getting glucose or sugar into the cell and therefore lowering or regulating blood sugar levels. Well, all well and good, but I think that we have a tendency to be really myopic when we assign our understanding of insulin or other things in the body, other metrics, to a specific area to, to the exclusion of other functionality. And, you know, for example, we say, well, testosterone is the male hormone. You know, women need testosterone.

Very important. Progesterone was named because it's progestation. It's the, you know, a female hormone that goes up during gestation. Why would my body have progesterone receptors? I think it's important to expand, in this case, on what insulin does in the human body. And specifically vis-a-vis our conversation now, how does insulin relate to? the brain. Well, insulin does play a role in allowing brain energetics. We'll come back to that in a moment, but it's the way that blood sugar gets into the brain glucose to ultimately lead

to the powering of the brain cells, the neurons specifically, and that's really important. When our bodies become insulin resistant, we'll talk about how we get there, I guess I'm paving the way for a lot of conversation, then that functionality, brain energetics is compromised. that's a bad thing. We can scan brains 20 years ahead of time and determine already when there is compromised brain energetics that is the harbinger for future cognitive decline and ultimately Alzheimer's disease. And that means tangentially that, you know, the choices we make in our 30s, 40s and 50s are very relevant because they again portend cognitive decline and full-blown Alzheimer's disease. Other things, however, that insulin does, I think are very important. For example,

we know that insulin is degraded in the brain by something called, oddly enough, insulin degrading enzyme. Well, it turns out that when we're unable to stimulate adequately this insulin degrading enzyme because insulin functionality is compromised, that that same enzyme is involved in the degradation of this protein we referred to earlier called beta amyloid. So that's now a connection between insulin and beta amyloid. We know that insulin is important for, again, regulating blood sugar. And why is that important? Because when our blood sugar is elevated, we change our proteins via something called this process of glycosylation, where proteins bind to sugar. And that's an issue because not only does it change what the proteins look like in terms of their three-dimensionality,

but it also, because of those changes, alerts the immune system that, hey, here's a protein I've never seen before, and what happens? The immune system gets activated and inflammation gets turned on, and inflammation is really a central player in what degrades the brain in Alzheimer's. So the point I'm making then is regulation balancing our blood sugar, keeping our blood sugar under control, is while everything is important, I think that might well be perhaps the most important issue. You know, in terms of what throws the widest net, in terms of for your viewers, what they need to pay attention to, that this blood sugar regulation is in the front row and that we need to do everything we can, getting back to diet, and I know you wanted to move past that,

But I chose not to because it's so important, something we all make choices about every single day, unless we're fasting, of course. And everything we can, with reference to diet, to keep blood sugar levels under control, basically lower than they might otherwise be these days, I think is very relevant. You know, utilizing things like continuous glucose monitoring, checking our blood for ketones, being really aware of fructose in the diet. so many things that influence blood sugar, our sleep patterns, our exercise patterns, sleep as we measure with our wearable devices. All of these things play into balancing blood sugar levels, and the brain is exquisitely sensitive to its provision of its fuel, which is basically glucose, and when that's compromised, when that is threatened, that really does set the stage for future to climb.

I'm glad that you doubled down on the diet. I did want to cover diet. I was going to cover a few other things, but I'm glad you actually forced it in the direction that you wanted to go in because it's just another reminder that just like we say, you can't exercise your way out of a bad diet. If you're serious about brain health, you cannot approach the topic without thinking about blood sugar regulation.

And I think that's an important message for our listeners, and it's a hopeful one because that's actually something that's largely in most people's control and will continue to be in their control as they start to use wearables like CGMs. And I know you're affiliated and I'm affiliated with a company that's doing some great stuff in that space. We'll chat about them a little later on. So I'm glad you doubled down because I think that is just an important thing for everybody to remember is that we're looking for sometimes the right supplement in the traditional world of medicine. It might be actually what medicines are there that you covered earlier. But it really has to come back to

core blood sugar regulation. While we're on that topic, you're not just talking about sugar and high levels of sugar in the diet or in added sugar in the foods that are there. Even for people that consider themselves quite healthy, there's other forms of things that are regularly part of our lifestyle today, even in the world of modern wellness food, that are consistently throwing off our ability to regulate our blood sugar. What were some of the surprising things that you found over the years and putting your books together that act the same as sugar inside the body. Well, that act the same as sugar in the

body. Let me just take that back a little bit. And what are the surprising things that I found that really plays such a central role in blood glucose regulation is a different sugar called fructose. You know, the amount of fructose we are consuming now is, I think, breathtaking, seeing that table sugar is 50% glucose and 50% fructose. That's what sucrose for table sugar is. But now we're seeing our foods peppered, wrong term, sweetened, with what it's called high fructose corn syrup, which might be 52% fructose,

but in reality, maybe as high as 90% fructose. Now, the messaging on fructose over the years was, hey, that's a better choice than eating glucose, because fructose, unlike glucose, does not elicit this insulin response that we just spoke about. And while that may be true in the short term, we know that ultimately, through its unique metabolism, that fructose is extremely threatening to the way that insulin works in the body and ultimately leads to elevation of our blood sugar, elevation of our blood pressure, dysregulation of our lipids, increased risk of obesity, increased risk.

of other metabolic issues. So, you know, we've been told that fructose is a safer sugar. Even the American Diabetes Association did until quite recently recommended fructose as an alternative to glucose or highly refined carbohydrates in general. So I think we now understand, we'll get to this later, that through its production of something called uric acid, that fructose is a powerful threat for our metabolism, therefore elevation of blood sugar and then this increased risk of insulin resistance that we talked about just a moment ago. But, you know, I think that we could take this conversation to a lot of places. We can take it to the gut bacteria because we know that the signals sent out by our gut bacteria have a huge role to play in regulating our metabolism.

There is well-described changes that can occur in the gut bacteria. bacteria that paved the way for insulin resistance. And in fact, we know that that is a direct response to the various foods that we eat. But I think, interestingly, we can look at how these changes in our gut bacteria brought on by, for example, consumption of fructose and therefore leading to higher levels of insulin and blood sugar may have been in our hunter-gather days quite adaptive because think about it. When did we eat fructose? When did we have fruit sugar? We had it when the fruit was ripe and before modern agriculture, fruit is ripe in the late summer, early fall, signaling to us that winter is coming, winter a time of caloric scarcity. So fructose changes our gut

bacteria such that it prepares us for winter because our gut bacteria get the fructose signal and say, hey, winter is coming. We need to change. metabolism here and starts storing fat and reduce the burning of fat so that we keep it around. We actually have to make more glucose, a process called gluconeogenesis. So it's the response that we get from fructose not only in terms of our gut bacteria, but also in terms of what has created the downstream metabolism of fructose, which is uric acid. Uric acid is the danger signal saying winter's coming, not going to be a lot of,

of food, you'd better make fat, you better store fat because you're going to need it if you're going to survive. And we have higher levels of uric acid because of an unique series of mutations that occurred in our primate ancestors 14 to 18 million years ago, whereby we have much higher levels of uric acid. So those ancestors in our primate lineage who had those mutations survived. And now you and I and every other human walk in the planet has an increased production of this uric acid such that we make fat, we store fat, our blood pressure is at risk for being higher. We develop non-alcoholic fatty liver disease and we develop dyslipidemia, higher levels of LDL and cholesterol, because these were actually protective of us in the day. So what I'm describing then is what is called an evolutionary environmental. mismatch, where in our past, these mutations, these changes to our metabolism allowed our

survival. But now, because of the different environment, being pounded by fructose, day in and day out, lack of restorative sleep, lack of enough exercise, you know, we'll talk about these things, and, you know, challenges our genome. And it's really, I think, the fundamental of the so-called paleo movement that we really need to respect our paleolithic genome and give it the signals that we can control that it wants in order to keep us healthy and allow us to survive, allow us to procreate, and allow us to be disease-resistant. It's such an important point because so many times when people, whether they're in the wellness world or they're just, you know, somebody who's just trying to live their best life,

this is not an area they study, they may not be listening to this podcast, anybody who's dealing with extra fat on their body and has struggled with it for a while feels that their body is working against them. They feel that there's something wrong with them. They feel like even some cases I've heard people go to an extreme and feel like their body is almost punishing them. And what you're really highlighting here is that your body is doing exactly what it was designed to do. It's just we're giving it the wrong signals. It's constantly preparing for winter based on the way that we're eating, living, and going about our modern lives. It reminds me of a story that I was hiking up in Glacier National Park up in Montana, near and by the border of Canada. And I was with

the guide. And she was like, you know, there's this really cool edible berry that I want to show you. And it was about end of September getting ready for snow season, October up there, especially at higher elevation. She said, let's go through this path over here. We went to that path and the berry bushes were there, but all the berries were gone. She's like, oh, the bears actually came in and must have eaten all the berries. They're getting ready for hibernation, so they're eating as much fruit as possible because they're going to go hibernate over the winter, and so they need to store all that fat. And so in that same way, we're going around in our diet between the grains that we're eating, the fructose that's in our diet, the severe blood sugar dysregulation, the overproduction of

insulin, we are telling our body, winter is coming and we better get ready. You know, one of the things that I'm sure you've seen this too with a lot of people that follow your book, blood sugar, if we look back actually and zoom out at sort of dietary trends in America, starting first with sort of Alice Waters, you know, the sort of farm to table movement, the rise of sort of vegetarianism in the 60s with sort of the hippie culture and that sort of thing like that. And then coming into nowadays clean eating and then more hyper-reaching. focused areas, personalized nutrition, blood sugar regulation and managing your blood sugar is a new concept for a lot of people because we're used to thinking in terms of, you know, good and bad, right? So if somebody's vegetarian, they think, okay, meat, you know, and I'm not, and I know you're not, but just looking from their lens, okay, meat is bad and then this is good, or this is good and this is bad if somebody eats a particular way like gluten-free or whatever it might be. But blood sugar regulation and paying attention to that, it almost is like, look,

any diet can work for you and every diet could also work against you. There's actually a ton of products that are on the market that are called keto that when people are using things like levels, continuous glucose monitor, they're seeing that actually this thing is raising my blood sugar more than anything else that I'm eating right now because it's this processed snack that's there. So I'm very excited and I'd love to get your thoughts on a personal level. You know, as you've been monitoring your own blood sugar and making it make sense for you and your life and your level of activity, have you been surprised at what things might move the needle in the right or the wrong direction when it comes to your own blood sugar management? Yes.

And I think it, you know, more broadly, it is great information. we can all learn personalized medicine for ourselves based upon the input from wearables these days and learn things like I didn't realize cashews were such an issue. And they were for me, for whatever reason, eating cashews bumped up my blood sugar. I also recognized that my blood sugar was not as ideal with not a really good night's sleep. So a lot of correlation between the metrics of my sleep, again, as determined by a wearable and what I would see on my CGM or continuous glucose monitor. And I think, you know, that's sort of the beauty of what levels is doing is allowing us to

see it in real time and then to make those correlations. But, you know, I think that what is most important is not to define the best diet for everybody. And that's been the trend. Everyone should be vegan. Everyone should be keto. everyone should be paleo. And I think what is more valuable is to define the goals. What are we trying to achieve with our diets?

Certainly, as you well mentioned, that control over blood sugar, keeping blood sugar in check is a certainly valuable goal. if you want to take it further than keeping uric acid in check, keeping other inflammatory markers in check, all well and good, having a diet that caters to the gut bacteria, a diet that's rich in polyphenols, antioxidants, all well and good. But I think these days we have the ability to personally obtain the metrics that can then reveal the value or the threat imposed by the dietary choices that we make. That's the science part.

there's a social part to our dietary choices as well. And, you know, we leave that up to the individual. But all roads lead to Rome. I mean, we can adopt any of the popular diets and modify them to reach our goals. Like you say, what might have raised my blood sugar might not raise your blood sugar, but we can determine that when we're careful and we start doing a little bit of science and understand that we're all different. We all have certainly different genomes. We all have, We all live in different places. It's varying times of the year. Seasonality varies across the planet.

And perhaps, most importantly, aside from our genome, our microbiomes are very different. And the array and diversity and numbers of organisms living in the gut are really influential in terms of how we interpret the foods that we eat and how it plays out in terms of measurable metrics like blood sugar. for example. So I think gaining that information through the technology that we have as individuals, apart from what we can get in the doctor's office, I think is exceedingly valuable. And it gets back to an earlier part of our conversation where we were developing, we went somewhere else, but we were developing a dichotomy between just the notion of sort of living your life however you want and then hoping for an Alzheimer's drug versus really beginning to impress,

embrace the notion that our choices have huge impact in terms of our brain's destiny. And that, you know, that's a wedge being drawn in our society right now, being, you know, really tending to really reveal how polarized we are that the mainstream would have us believe that, you know, there's another drug down the pike coming soon enough that'll save us all and getting excited about a drug that slows the progression by 32%. that all well and good. But I am not really interested in a drug that'll slow Alzheimer's progression by 32%. I'm interested in lifestyle approaches that can reverse that problem, for example, and put people back on their feet.

And that is, again, in the realm of personalized medicine, what does that individual need? It's much more important to know the person who has the problem rather than understand the problem the person has. You were mentioning the gut bacteria earlier. I have another question for you on a personal level because people are always interested. And obviously your experience is your own experience. It's not necessarily going to be everybody's experience. But it highlights, again, this theme of personalization. So just as you mentioned, you know, for you, cash shoes, that was something that you were highlighting.

Again, just for you that you've monitored and you saw. No, I love them. Yeah. Though you love them. And I'm sure you have them occasionally. And it might just mean less quantity, right? And being aware. Is there something on a gut health.

level that you find doesn't work for you. Like sometimes people see that, you know, even though certain types of dairies might actually could be beneficial, right, like super high quality dairies or goat's milk or sheep's milk, you know, I personally know for me, yeah, I personally know for me that, you know, dairy, no matter how high the quality, I have to be very careful about the dose because I still am very reactionary, probably because I was on a lot of antibiotics when I was younger and, you know, decimated a little bit of my gut bacteria. When it comes to your gut health, you know, and we're also eating for our gut, are there foods that you just know that don't sit with you as well, if there are any?

I would say that that's more of a cognitive prefrontal choice rather than, you know, more of an emotional or a visceral kind of a response. I don't have any real intolerances that I can experience or I have experienced and therefore know that that particular food isn't good for me. You know, my choices come from more of an understanding in terms of the value of a particular food or the threat of a particular food or lifestyle choice or medication, you name it, in terms of the gut bacteria. Give you an example. Last week, I had surgery on my shoulder, and I was given a prescription for an antibiotic to keep the wound from being infected and made sense to me. I mean, you know, my career started off in general surgery, then neurosurgery,

and that was standard operating practice. So I know what a threat that you just mentioned it, you know, how your early life experience was. I know what a threat that is. you know, antibiotics, though they can save lives and are very important part of our armamentarium, nonetheless, they are weapons of mass microbial destruction in the gut. And I liked it not to take it. And so far so good, I'm four days into it. My wound looks just fine. So I think I'm going to be okay. Do you know, would there have been an upside to taking an antibiotic in terms of reducing risk of

infection, yeah, I would think, but knowing the downside, knowing the risk, knowing the relationship between antibiotic exposure, for example, and the development of type 2 diabetes, well described. In women, antibiotic exposure is associated with an increased risk of breast cancer. We could certainly talk about antibiotics and non-sorotal anti-inflammatories and acid-blocking medications and a host of others that are directly threatening the gut bacteria. So I think that these are choices that I make less on how it feels to me as opposed to what I understand about the science and then taking that information and getting it out in any possible forum like chatting with you today.

That allows me to get information out that would be helpful for people in terms of catering to the health and diversity of their gut bacteria. It's really, really important. Matter of fact, interestingly, a study was published this morning that was sent to me by Dr. Stephen Gundry. You may have heard of Dr. Gundry, has done a lot of work on lectins and a terrific guy, cardiologist. And the study had to do with this very, very primitive tribe that's often studied in

Bolivia, where they have what looks to be a very very very. primitive array of bacteria in their gut, microbiome. And it looks like their microbiomes, when it's sequenced, emulates what our ancestors from thousands and thousands of years ago had in their gut. We're actually able to determine that from looking at fossilized poop. We're still able to recover markers that allow us to determine what the bacteria was like. Anyway, the study today said that these people who are infested with all kinds of of bacteria, but beyond that, all kinds of worms and other parasites, that they demonstrate

larger brains, reduced risk of cardiovascular disease, and really preservation of their bodies as they age in comparison to age-matched individuals living in modern society. So my point is that, you know, this relationship, we've been talking about since we started today, this relationship between what our gut bacteria are doing and their diversity, what we, is huge and extremely valuable. We're just beginning to understand it and therefore be able to tap into it as another powerful tool in the toolbox. I interviewed a Dr. Molly Fox several years ago, a researcher who in 2013 published a report

that correlated Alzheimer's risk with what's called hygiene, basically. And the marker of hygiene was looking at how many parasites were in the gut. Those countries, she looked at 100 countries around the world, those countries around the world that had poor hygiene, as evidenced by higher levels of parasites in the gut, had the very lowest risk of Alzheimer's. Countries with great hygiene, you know, countries in Northern Europe, the United States, et cetera, that are very much invested in hygiene, keeping us sterile, keeping us clean,

keeping our kids from playing in the dirt, had the highest levels of Alzheimer's. A correlation, certainly back in 2013, just a correlation, though I've interviewed her more recently. And now that we understand mechanisms whereby the gut bacteria are regulating what we've been talking about, our blood sugar, regulating the set point of inflammation, regulating the set point of inflammation, regulating autoimmunity. I think it becomes extremely valuable information as you relate to understanding the relationship moving forward and what we can do about it between the gut and the brain.

I think the take-home message here is to just embrace the incredible role that these bacteria and other species are playing in the gut in terms of regulating so many important aspects of our lives, whether it's our metabolism, whether it's our mood, whether it's our brain functionality moment-to-moment immune system, that's for sure. Even our gene expression to some degree is regulated by some of the products manufactured like short-chain fatty acids by the very bacteria that live within the gut. Maintaining balanced blood sugar levels and implementing lifestyle practices to support our gut health

has so many beneficial implications for our overall health and our brain health. specifically. And my conversation with Dr. Lisa Mascone, she further breaks down how what we eat is so impactful to both our metabolic health and to preventing cognitive decline. Dr. Mascone also shares what happens metabolically while women go through menopause and why our lifestyle practices play such a huge role in supporting our brain health or, if done incorrectly, brain dis-ease. Let's listen in. The brain is the most energetically expensive organ. And it does run on glucose, no matter what other people think, it runs on glucose. There are other energy sources as well, but at least through menopause, every time you burn

glucose for energy that is oxidative stress that's been produced. And if the amount of oxidated stress and free radicals exceeds your brain's ability to detoxify, which is not the trendy term necessarily, really the brain needs to get rid of this free radicals. articles. Medical detoxification in the medical. Yes. The only way is to supplement from the diet. So you need to import antioxidants from your bloodstream. It's basically the only way to supply antioxidants to the brain. And it's a very important thing to do because antioxidants just damage everything. They have a rusting effect to make yourselves age faster. They impair metabolic reactions. They impair cellular reactions at all different levels.

They'll age you. They'll age, yes. Yes, you can't see it. Hit it with the vanity, right? I mean, people do see it. People who eat ultra-prassless diet, they see it in their skin. Yeah, yeah, I meant you can't see it in your brain that it's aging, but you can trust the science that it is. So I think it's really important to focus on foods that have reached an antioxidants,

and those are fruits and vegetables and some nuts and seeds, some whole grains as well. So it's one more reason to, you know, there's this way that people, this terminology people use now to go plant forward, right? And I think it's a good way to think about it. You want to up your consumption of produce, basically. Fruit and vegetables, if you don't eat fruit, at least eat the vegetables. Because they really are the best source we have of readily available antioxidants. Most people think blueberries and blueberries are a wonderful thing to eat.

There are other foods that provide even more antioxidants. like blackberries, if you like berries or goji berries, or the Indian berries called Amla. Yes, is one of the most, you know, powerful foods in terms of antioxidant capacity. Artichokes, highest antioxidant capacity of all veggies, as far as I know at least, goji berries, great source of vitamin C, some little plums

are also really good sources, and then lemon, orange, grapefruit, and leafy vegetables, cruciferous vegetables, all sorts of vegetables. Those are really important for brain health as well. Also, they contain fiber. And fiber is important not only for digestive health, for a healthy microbiome, but also to regulate estrogen levels. So fiber has a positive effect on this protein, this called the sex horribalum.

hormone binding globally that regulates the amount of free estrogen relative to bound estrogen. So it regulate endostostastosterone and other hormones, but it regulates bioavailability of these hormones in the bloodstream. So it's important to eat fiber for the reason as well. And then there are very specific nutrients that provide nutrition for the good bacteria in the gut. They're called oligosaccharides. there are type of carbs that we don't really fully digest in the stomachs, so they land in the intestine almost untouched,

and this is what this good bacteria that we have in our guts, the microbiome feeds on. And there's one interesting part of the microbiome that is called the Astrobolome that has been discovered recently that is a part of the microbiome that specifically helps to regulate estrogen levels in the blood, and you know, you can damage these microbes by eating processed foods or not eating enough fiber in your diet and by taking antibiotics or by ingesting other chemicals that can disrupt your flora, your intestinal flora, or you can keep them healthy by making healthy choices

and eating enough fiber and drinking enough water and having enough for the antioxidants and anti-inflammatory foods as well. So there's one more reason to go plant forward, if you will, which it really can just come down to eating enough fruit and vegetables throughout today. Beautiful. I love that. You have a new book all about the menopause brain. Talk to us about that time in a woman's life. What is actually fundamentally going on in the brain?

And I believe you also have some incredible scans that can help illustrate the message and really, really, drive at home as well too. Yes. So my research, as you know, I'm a brain scientist by training and I do brain imaging or brain scans for a living and they usually focus on Alzheimer's disease, the risk of Alzheimer's and how to prevent Alzheimer's disease, especially in women. And there was my research on cognitive aging and dementia that led me eventually to study menopause as a risk factor for Alzheimer's disease and cognitive aging in women. So this is an interesting connection. There was not really fully explored until we came along.

In some ways, there was a lot of preclinical research. But what was missing, I think, from the picture was a very clear illustration of how menopause can impact the brain as women go through it. So there was research showing what would happen, what can happen to women's brain health after the fact, right? So insofar as research had any interest, the menopause until 2017, it was always in terms of the outcomes.

So menopause was seen more as an endpoint rather than a process. And for me, the question is what happens during, right? Can I catch any changes by looking at women? women's brains before, during and after menopause. And to me, as a woman, besides a scientist, I was shocked to realize that it really had not been done. There was 2017, I come from a completely different line of research. And I was like, okay, I understand that menopause is so important for women's brain health.

What's been done already? How do we build up on it? And nothing had been done in terms of. of before and after. So I went to my team and I said I realized that this is different what we've been doing for the past 15 years, but we need to. We need to do it. And so we gathered, we enrolled a lot of women in the study and we started doing brain scans and we were able to map the neurological effects of menopause in women going through the menopause transition. So these are the brain scans.

There are some of the brain scans that we've been, that we're done. So when we started, we had 60 women in the study, 20 premenopausal, 20 perimenopausal, which is the in between, 20 postmenopausal, and we compare them cross-sectionally, right? One woman against another woman. But the real question was, what happens to you as a woman, as you yourself, transition from a reproductive to a non-reproductive state? Is it just your ovaries that change? Does that really impact your brain? So, let me show you.

Yes, yes. Well, we started gathering evidence and now more and more investigators are trying to do the same. So we have more data. We have more information, which is really great. This is one of the very first patients who has been working with us for many years. Because going through menopause takes a while. By the way, most people think it's like overnight. Absolutely not. It can take a decade to fully go through menopause.

Now, we worked with a woman, many women, but this is a patient who was 43 years old. Yeah, and we're looking at scan of her brain right now. Yes. And she went through menopause a bit early, and we can talk about that. Right. Why some women do that? Why other women, it's more delayed. Exactly what the range is. But the important thing is that we were able to map her transition in a reasonable amount of time, right, in like less than 10 years, which means she's been with us for 10 years at this point and I've been doing this forever. This is 10 years of my life.

But yes, so this is the type of brain scans that I specialize in. This is called the positon emission tomography or pet scan that looks at broadly brain energy levels in the brain. We use a tracer that's called fluorideoxid glucose. which maps the intracellular concentration of glucose, a simple sugar in the brain. Why? Because the brain runs on glucose.

So glucose is the primary energy source for the brain. So this is like the fuel that the brain utilizes to produce energy or ATP at the cellular level. So this kind of brain scans shows the speed at which the brain takes up glucose from the bloodstream and converts it to energy. So it's awesome, isn't it? It's great.

It's amazing. Yes. And you want your brain to look really red when we're using this color scale. It's showing a positive usage of energy inside the brain. It shows that your neurons are hungry for energy and they're burning energy, they're burning glucose efficiently, which is wonderful. It's a sign of a healthy brain. And you want your brain distribution to be mostly like this.

So isometabolic, which means that the left side of the brain is this bright. is the right, it's kind of symmetrical. In the top, it's just called the frontal cortex, it's brighter, but almost as bright, as the very bottom part there, which is the precunius, or the parietal cortex, and posterior singular cortex. And then you want just little structures in the middle that looks like, I didn't really know what it looks like,

but the little butterfly shape in the middle, just the salamis, the basal ganglia, to also being really nice and bright. So this is a wonderful looking brain. Yes. This brain has all those things. Yes, this brain has all these things. Yes, this is what you want your brain to look like when you're like in your 40s.

So really nice and bright with a lot of red and a lot of yellow and a lot less green and blue. Okay. But then we're superimposing the after menopause scan on the before menopause scan so that we can really see the change. the change in the brain. And I think you can see how the red turns yellow and the yellow turns green and the whole skin, the whole brain turns greener. Yeah, there's a lot less red in the brain.

It's like fading in a way. And we're going to look the image so we can see it again. Right, so this is a boom, bright. Now you see it's really, really red, very activated. And then pretty much the whole cortical mental declines. in terms of energy utilization and production. So we can put them side by side. And remind us over what period of time was this?

Yes. So the after was before age 50. So that may have been like less than seven years. Seven years. So these are over a seven year period that transitions slowly, slowly going from a lot of red to a lot of green. A lot of green. Which is a 30% reduction in brain energy metabolism. It's it's.

That's a lot. Yes, it's significant, I would say, especially in seven years, right? Not all women show these changes. Not all women go through menopause in seven years. Usually it takes longer. But I think this is a really good example of what can happen, metabolically at least, as women go through menopause. So there's no, I think it's obvious, the after scan is different from the before scan, which was taken by many as conclude. more conclusive evidence that menopause impacts the brain, right?

Menopause changes the brain because really many clinicians still don't believe that. Many scientists do not believe that or are not aware of that. So I think that this was very helpful to many to see, oh, now we have evidence that I can actually discuss and talk about. There's something that I can see, that I can quantify and measure is not just women's imagination. I don't know why we have to clarify that, but evidently we do. So I always say our work is largely about validating what women have been saying for thousands of years and providing a good level of evidence that this is true.

It's not just all in your head like many people believe. So we're legitimizing women's experiences for centuries. basically and we're trying to raise awareness that this is not just something that happens in the brain and stays in the brain. There's behavioral correlates, there's symptoms, there's medical risks to come from these changes. Yeah, this work is phenomenal. And just to kind of connect some of the dots there, in the book you say, this is not just about the ovaries. Yeah.

It's about the brain, which is how science looked at it and medicine looked at it for many years, is that simply this is a woman who is no longer reproductive. and that's just about the ovaries. That's about it. And there's the lived experience of millions, billions of women over the years, talking about how they notice their brain changing, their body feels,

a whole host of different things, often a negative association with that time. Women sharing like, here's all the negative things that I'm experiencing that I previously wasn't experiencing, which we'll chat a little bit more about that. And it also lives in this, context that, yes, this is the lived experience of modern woman that's there. And there could be conditions that are happening in the way that we live today that are magnifying what would be

associated as some of the more symptomatic issues that women are going through during this phase of life. Is that accurate? Oh, it's perfect. Yes, it's completely accurate. And thank you for saying that. I think as a society, we have missed pretty much 50% or half for what menopause really is. So menopause is a neuroendocrine transition, which means that your brain and your hormones are all in transition. Your reproductive organs are changing and your brain is changing accordingly. But if you think about the way the menopause is perceived in society is all about fertility. So most people realize that, yeah, something is happening to the ovaries, and then you're going to stop having a menstrual cycle. You won't no longer be able to have children.

So menopause is usually seen as the end of fertility. And because in Western societies, most of the Western world, really a woman's worth is usually associated with her ability to carry out of pregnancy and have children. That menopause is seen in the extreme negative as something that is a problem. problem for women that we need to either completely ignore and not talk about or heavily medicalize. And I think it's really important that we get a clearer picture of menopause isn't and isn't. And that really starts with understanding the connection between the brain and the reproductive

system. And this is important not only for menopause, but for life, right? So I try to clarify in the book and in my talks and in my work also. that we think of aging as a linear process, right? You're born and then you grow and then you age and this kind of linear overtime and stable. That is not the case for men or for women. There are very specific transition states that accelerate growth

and then accelerate in others that accelerate aging. So it's more like a step-bloader of sort. And for women, there are three. three very important pivotal times, which I call the three P's, puberty, pregnancy, perimenopause, which is the transition to menopause. Can I talk more about it?

Please, please. Okay. Let's jump into it. So I think it's so important to realize that we are born with a very important system in our bodies that connects the brain to the reproductive organs. We never talk about this system, but it's right there. and it's a strong driver of brain health and longevity

for both men and women, right? So we are born with a sort of gigantic system, that neurological system that connects the brain in women with the ovaries and the men, the brain with the testis. This is called the neuroendocrine system that connects the brain, your neurons, to your hormonal system, the endocrine system. And in women,

this system is actually activated as we go through puberty. And that leads to a complete remodeling, as we all know, of the body from the neck down, but also of your brain. Your brain changes massively when all human beings go through puberty. We can talk about it if you like a little bit more because it's important to understand pregnancy and that menopause and women. But then this same system is really, reactivated during pregnancy.

Every time a woman goes through pregnancy, it's not just the body, the changes, you're not just having a baby. You are effectively remodeling your brain to prepare for motherhood. And we just really never acknowledge that as something that is worth being happy and proud of, you know, and I would love to change the narrative around this as well. And then the system, however, this neuroendocrine system is shut down after menopause because you no longer need to have kids. So this very elaborate and metabolically expensive system has no reason to be there anymore. So we're going to turn it down, which is a way more efficient way to live and move forward than just keep carrying all this infrastructure you no longer need.

But that leads to another remodeling that in this case comes with some glitches, like the symptoms of menopause that everybody is concerned about and there's so many women experience. Over 80% of all women experience neurological symptoms during menopause, brain symptoms. They just don't realize that those symptoms come from the brain. So when women say that they're having heart flashes, night sweats, insomnia, depression, anxiety, panic attacks, memory loss, forgetfulness, brain fog. Those are all symptoms of menopause that do not start in the ovaries at all.

They start from the brain. Their neurological symptoms, we're just not used to thinking about them as such. And therefore, we don't quite know how to address them properly because menopause means obegin territory, right? But half of this transition is actually neurological. and there are no brain doctors involved. In fact, you also add to that inside of the book, you say that these symptoms in this transition

in a woman's life is also associated with sort of a negative sort of happiness index, right? Like they're, like that, I don't know exactly the proper term, but they report to feel not as content, not as sort of joyful during this period of time. And then on the other side of it, you end up transitioning and feeling much better. Do you want to see it?

Yes, please, let's do it. There it is. Describe this for the people that are listening. Yes. So these are quite a few studies that nobody seems to know about. They're mostly from Europe and some from the United States, where scientists have very creatively started thinking of menopause, not as a loss or as a medical issue,

but there's something that has a reason to be. And it's the grandmother. The grandmother, the grandmother, we were talking. about before. But this is what the data shows, right? So before menopause, let's say your life satisfaction starts at whatever level on the y-axis, right? So it's pink, the pink line. For many women, life contentment and happiness takes a dip during period menopause, which is the transitional phase during which we start skipping periods and all these symptoms can make the first appearance and usually hit you hardest, the half flashes and forgetfulness, the depressive

symptoms, lack of sleep is a huge one, right? And life satisfaction goes down accordingly, which honestly is no wonder, I would say, many women report not being as happy or having a hard time. But what was striking to me is that once the transition is complete and we basically we merge into the post-menopause stage. At some point, like two or three years, sometimes up to six years after the final menstrual period, life contentment resumes and it starts increasing.

And at some point for many women, it would be even higher than it used to be before menopause. And what's important is the variability, right? So we have the pink line that shows the average change. but then we have a lot of variability, which is the pink to blue shadow behind, which really says if menopause was the same for all women, we would have very little variability, right?

But the variability is huge, also due to imperemenopause. It can range from the very top of the curve to not having any issues. Your life satisfaction pretty much remains the same to being extremely sad and depressed. And the outcomes are generally part positive, but they're more positive for some women and not as positive for other women. So the question for me was, why? What are the factors that can make menopause better for you?

What are the factors that can help you or not? How do we prepare? And how do we keep our brains healthy after the fact? So a lot of my research now is really focused on menopause and specifically hormonal transitions for women. And men, we're starting a program for men as well because, you know, not everybody realizes that men go through a sort of menopause too. It's called andropause, which is different, is more gradual and usually hits in the 70s and 80s, but it does happen. And there are hot flashes and there are sleep disturbances and there are just forgetfulness and other concerns that I think are very important to investigate for. for men as well and then address.

I believe that lifestyle plays a crucial role in brain health overall. And you and I have talked about this before. And I think this is especially true when it comes to menopause as well as puberty and pregnancy. It really, the way you live your life and the choices you make have a huge impact on your health, not just your physical health, but your cognitive health and mental health as well. And one reason for it that I like to discuss is is that the brain is not like the other organs in the body. So most of our organs, the cells and most of our organs,

regenerate continuously. There's a very rapid turnover. So if you look at your blood cells, they're constantly, they're constantly discarded and regenerated every three months, right? If you look at your hair, you lose hair very often, but then it regrows. Even the skeleton is renewed. at a rate of 10% a year. So whatever change you make in your lifestyle,

whether it is diet, exercise, stress reduction, you can see the effects very quickly because your body is optimized for change, not your brain. Your brain is optimized for stability. So neurons do not regenerate. Some can grow over time, but most of the neurons we have

are born with us and stay with us for life. So the best way to have a positive impact on your brain health is to be consistent, right? This is why quick fixes do not work from brain health. These three weeks magic plans that people try to sell, not happening when it comes to brain health. Because if you could change your brain in a matter, in a matter of day, we would all be mad, right? We need to protect. It's good that your brain is stable. It's not so easily influenced. But the changes then are long-lasting. So lifestyle practices that are done consistency frequently enough for a long enough period of time have the best chances of making a positive or negative impact on brain health. There's so much we can do today

that can have a huge influence on the way that our brains will show up tomorrow and in years ahead. And while we don't always think about the implications that things like blood sugar levels, gut health, and overall metabolic health have on our brains, I think today's episode is an excellent reminder of just how important these things are when it comes to protecting our brains and our cognitive health. So if you like this episode, a huge favor, a huge ask, share this with someone that you know that is maybe a little bit worried or feels a little bit out of control when it comes to things like Alzheimer's or cognitive decline and a little bit of information.

A little bit of knowledge, a little bit of hope that there are things that we can do today to improve our life tomorrow could make a huge difference in their life. So share that episode with them. And if you want to hear the full-length version of any of these conversations featured today, Dr. David Perlmutter and Dr. Lisa Mascone, you can find those links in the show note episodes in your app. Until next time, Drew Prood signing off. Thank you for listening in.