Transcript of Episode 583: Dr. David Perlmutter: Brain Health Expert: The Daily Habits That Protect Your Brain as You Age New

Hi guys, it's Tony Robbins. You're listening to Habits and Hustle. Crush it.

Welcome to Habits and Hustle, where I sit down with the world's biggest thinkers, entrepreneurs, top experts to uncover the habits, strategies, and mindset shifts that actually move the needle in your health, happiness, and success. And today I'm sitting down with Dr. David Perlmutter, a board-certified neurologist, bestselling author, and leading voice in brain health and neurodegenerative disease. We discuss why protecting your brain starts decades before symptoms appear, how inflammation and metabolic health impact brain function, and what you can do now to reduce your risk of cognitive decline. We also cover loneliness, sleep, strength training, oral health, fasting, and insulin. Oh my God, the list goes on. This conversation is packed with practical ways to take more ownership of your brain health instead Waiting Until Something Goes Wrong. David breaks down that everyday habits, health markers, and lifestyle choices that actually influence how your brain ages, plus some of the emerging science that can completely change the way we think about Alzheimer's and other neurodegenerative diseases. So now let's dive in. Before we get into today's episode, I have a quick question. Do you ever hit 3 PM and feel ever feel like your brain's just done?

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Well, the circle is complete now, isn't it?

Yes, it totally is. The loop is now finally closed. Doctor, what do you want me to call you? David? Dr. Pearl?

David works.

David or Dr. Perlmutter?

I, you know, you see Dr. Perlmutter, I keep looking for my dad.

Okay, so I'll call you David. But yes, but I know, right? You still probably still look for your dad. I know, I don't like when my, when my, when my kids' friends call me Miss blah, blah, blah. I feel like a very old person. I don't like it. I like them to call me Jennifer. So David, or Dr. Perlmutter, has written his 16th book, and this one is called Brain Defenders. You may have read his book Grain Brain. There's so many, there's so many books, but we're going to talk all about the new book. And like I said, it's called Brain Defenders. I can never seem to see the— harness the power of your immune cells to protect your brain for life. So Thank you for being here.

Well, thank you for having me. And the subtitle really tells it all. It tells the story of the power of the brain's unique immune cells called microglial cells to really determine your brain's destiny, whether you're going to be along for the ride with your brain or the brain's not going to be there to participate in the rest of your life. So we fear things like Alzheimer's and Parkinson's and all of these issues that, you know, we run the risk of. But it turns out that we absolutely have a big say in determining whether that's in our future or not. And it all has to do with what's going on with the brain's immune cells, over which you have control. That's what we'll talk about today.

Yes. I mean, this is why, you know, I was really eager to have you on the podcast for personal reasons. My mother was diagnosed with Alzheimer's. I just came back from Montreal to see her, and she's now past the point of mild, I would imagine, in the mid area of Alzheimer's. And, you know, we talk a lot about preventative things. What I would love to hear from you is like, where is, where is the science or is there any evidence that you can reverse signs of Alzheimer's dementia if you are already past a certain point?

The answer is yes. How about that? Now, we've never been told that, have we? Uh, here in America, there have been FDA-approved drugs to treat Alzheimer's disease that, according to a recent Cochrane analysis, have abjectly failed. They do not have any meaningful effect on the time course of the decline in the Alzheimer's patient and are associated with a significant risk of side effects in at least a quarter of patients, either hemorrhage in the brain, swelling, or even death. And these are drugs that are FDA-approved. This is the best that pharmacy can offer us. And yet when we look at research, for example, there's a study that came out last year by a Dr. Rudolph Tanzi at, uh, at Harvard, along with Dr. Dean Ornish. And they took a group of patients who were diagnosed with Alzheimer's already, not at risk because they had diabetes or obesity or something. These patients were already diagnosed. 51 patients, 20-week study. What did they do? They changed their diets, they changed their level of activity, and they reduced their stress. And these individuals, it didn't slow down their progression. In 70% of them, it stopped their progression or led to improvement in their cognitive function.

There's never been any drug that could do that. And the side effects were the, uh, in these individuals that their blood sugars improved, their body weight improved, and they overall felt better. And think about that. And you're looking at me right now with a look on your face like, I haven't heard of that. And you should have heard of that. And you have it called, uh, it's lifestyle intervention.

But this is the thing, I'm looking at you like that, published in a peer-reviewed journal, and I wish you had of it.

And I'm not blaming you for not hearing about it, but I'm blaming the emphasis in our modern Western world to really offload the agency of our brain's destiny to a hope that a drug is developed.

It's—

I hate to say it's wrong. I sound so aggressive when I do that.

No, be aggressive.

But my dad died of Alzheimer's. And had there been a drug, would I have written the prescription for him? You bet I would have. I mean, his nursing home was— I could see his window from my examining rooms in my office. That's how close my situation was with his progressive downhill decline every single day. And so having said that, would I use the drug? I absolutely would have.

What was the drug called though again?

Well, there was no, there is no drug. There is, was no drug. The drug's okay right now.

Lifestyle.

Well, yeah, the drug is lifestyle.

Yeah. The drug is lifestyle right now. Yeah.

And you cannot patent that. It's not a billion dollar blockbuster.

You can't, you cannot patent that. This is what I know. But with your dad, though, you said that there was no, there was no potent, there was no, no drug or at that point. Right.

Nor is there now.

Right. There are these random drugs, but they have bad side effects. My mother was on one for a little bit. They took her off of it. It wasn't doing anything.

Well, here's the news. If they would do something, I would have a different conversation with you, Jen, right this minute. But here's what a recent Cochrane analysis revealed. This is the most highly regarded gold standard way of answering a medical question. Here is the two-part question. Part 1, does it work? Part 2, is it threatening? Is there side effects?

Right.

Are there? And here's what the Cochrane analysis of 20,342 individuals in 17 studies, 18 months each study, revealed, just published. Number 1, the threat of using these drugs is about 25% of people will have brain hemorrhages, brain swelling, or possibly even death. Die. What about the benefit? The word they used was trivial. So the drugs don't work and they're really risky. And that's very likely what they put your relative on and why they stopped it, because likely she was beginning to have side effects. And so, you know, it's not that your guest is really, as we talked about earlier, iconoclastic. You had a different word for it.

Irreverent. Irreverent.

Yeah. And I am, I guess. And I'm irreverent because I see, you know, my, my mission is above all, do no harm. And that's doing harm. And I will speak out about it. I talk about it in the book.

Yeah.

And that was before this Cochrane analysis that just came out to be supportive of what I'm contending in this book. And I'm certainly not anti-drug. We talk about the potential of GLP-1 Ozempic-like drugs to treat Alzheimer's.

I was going to ask you about that.

Am I open for that? You bet. Inflammation and metabolism. That story hasn't been fully written yet, and we're waiting for it. We can double-click on that at some point and really go do a deep dive.

I want to ask you about that now because they're saying even for people, there's a couple things. So you did, you do talk about the fact in the book, in this book, and you've said it many times that Alzheimer's is not genetic, right?

There's like, by and large, it is not genetic. Are there some genetic predispositions that an individual can have to increase her or his risk? Yes, there are. We know that carrying, for example, a variation in a gene called APOE4 is associated with increased risk. Either if you have one of those alleles, 5 times risk, or two of the alleles, in other words, APOE44, that your risk may be 10 to 12 times increased compared to others who don't carry it. There are other genes. There are about 60 different genes that play a role, but By and large, important message here. Here's the soundbite: Alzheimer's should not be considered a genetic disease. It's a disease related to lifestyle choices. That is very empowering because we can make better choices and reduce our risk. Genes load the gun, lifestyle pulls the trigger.

So just to keep on this for one second, and we won't, we won't need to drone on and on about my mom. Okay. But this is why, why I thought this was a very pertinent thing to talk about because you don't know my, you never knew my mother, you don't know her. But so she's also in the medical field. Interestingly enough, she did everything, everything right. Her blood sugar was completely intact. She worked out every day. She like physically, even to this day, she's not on any medication except vitamin D, physically top-notch, but her brain still declined. Now she did, this happened because in my, when COVID started, she was extremely isolated and extremely lonely because she was very, had a lot of anxiety around going to see people. Is to me, what that tells me is loneliness, isolation is probably predominantly more imperative or more of a trigger than let's say even exercise or nutrition. What'd you say to that?

I think it's incredibly underrated. And when we talk about the dramatic increased risk of Alzheimer's as a consequence of COVID You know, a lot of the discussion, at least in the medical science field, is what does the virus do? Does the virus increase inflammation? Yes, we know that. Does the virus affect mitochondrial function in brain cells and the brain immune cells, the microglia, the subject of this book? Absolutely it does. But you bring up an incredibly fundamental point that for a period of time, it may have been more than a year, your mother had a higher level of stress as many of us did. And isolation, and isolation is a huge event, especially as it continues as it relates to brain health. Why? The downside of isolation is increased stress and therefore increased cortisol, threatening to the brain's memory center, the hippocampus, threatening to the microbiome, the gut bacteria, and therefore increases inflammation that can shift the brain's immune cells away from being supportive to being destructive. The other thing though is when we are isolated, we're not experiencing love as much. We're not in contact with individuals that we share love with. And why could that be relevant in a— what we're having, I consider a scientific conversation.

And I wondered about that for a long time. When we looked at, for example, the Blue Zones, people have a lot of social connectivity, a lot of involvement in their communities, and have a dramatic risk reduction for Alzheimer's, heart disease, various forms of cancers, and other degenerative issues. But why, why Alzheimer's? What's the connection between connection and reduce risk.

Yeah.

And many things are at play. Cortisol lower, we know that. But here's something I found really fascinating. The book focuses on the shift of the brain's immune cells from being normally wonderfully supportive to help the brain remain resistant to decline, shifting to a situation where our brain immune cells basically turn their backs on us. They become what I call in the book the evil twin. A powerful way of keeping them supportive and loving and nurturing is to stimulate these cells called the M2 supportive immune cells. And one of the powerful stimulants to keep them in their supportive mode is a chemical called oxytocin, a hormone called oxytocin, the love hormone that increases when we have relationships with people. Your mom's isolation for whatever length of time that was Reduced her oxytocin and at the same time increased her cortisol. And the brain has, you know, significant experience with that. It bodes for a brain to be less able to resist decline. Now, you told me your mother's blood sugar was intact, that she exercised quite frequently, did all of the things. What Brain Defenders does is through the lens of the brain's immune cells, looks at those things and so many others that influence whether those brain cells are gonna be supportive or they will turn their backs on us and pave the way for the brain to decline.

Because you keep on, you mention a lot in the book, what you call, what was it called again? The immune cell micro—

Microglia.

Microglia. I've never heard that before.

And you are gonna hear about it left, right, and center moving forward.

See, that's 'cause you also, in another book, you talked about, you, uric acid was the other one.

Uric acid.

Uric acid. As I mean, so these are like, these are things that are not very usual, right? You hear about strength training, you hear about loneliness, you hear about, you know, even now I know you wrote the book Grain Brain, but like, you know, no processed, ultra-processed food. But these are, those are the two things that really kind of stood out to me. Can you talk a little bit about what an immune, like what immune cells are?

You are Canadian. Can I talk about?

Yeah, about.

You got me on the about.

There you go.

Yeah, sure, I can do that.

Yes, his wife's Canadian. Canadian.

So, and I have my—

okay. And your Canadian, yes, residence.

Yeah. So it's a new paradigm in neuroscience and it's exciting because—

how do you even get to it? Like, how did— like, after all these years of writing about it, like all of a sudden—

I didn't write about it for all these years.

No, no, I'm saying you've been writing about all of this neurology stuff for, for years and years, and now all of a sudden we hear about it.

And what is so exciting, Jennifer, is that everything I've written about, whether it's the relationship of the gut to the brain and the microbiome Grain Brain talking about gluten and talking about high refined carbohydrate diets, uric acid in Drop Acid, how that threatens our metabolism. Everything converges on the brain's immune cells. Finally, everything I've studied and written about and lectured about for 40 years has converged on the brain's immune cells. That's the upstream event in everything I've been interested in.

But what took so long? What took 40 years?

I think we didn't recognize that the immune cells in the brain, the microglial cells, threw such a wide net and were upstream of all of these mechanisms. And it's just come to light really mostly in the past 5 years. I've been talking about the microglia for decades, but we didn't really understand how they could change from being supportive to being destructive.

Right. So let's talk about that. So what— so explain what the microglia is and how it can go from being supportive to being destructive. Destructive.

And that's the take-home message of our time together today, because we can control it.

Yes.

Understand first that this is the upstream mechanism that underpins Alzheimer's and Parkinson's and MS and issues related to long COVID, PTSD, even major depression. All of these issues are fundamentally related to the change in the microglial cells from nurturing our synapses, nurturing our neurons and blood-brain barrier, to suddenly shifting and becoming the evil twin, destroying the synapses, actually gobbling up the connection of one brain cell to the next, setting up an environment in the brain that leads to the neurons falling apart and leading the blood-brain barrier, which we depend upon to keep the brain, you know, excluded from certain things, leads to that breakdown. Just like the gut barrier, we have a very important barrier in the brain that needs to be maintained. So many things can threaten to cause these cells to turn their backs on us. Elevated blood sugar, uh, changes in our proteins because they bind to blood sugar, like hemoglobin A1C. Increased inflammation anywhere in the body makes its way to the brain and sends a signal to these cells to shift and become destructive. Think about that. Where can that inflammation come from? A leaky gut. So your diet, whether it's supportive of your microbiome or not, through this mechanism of a leaky gut, can increase inflammation, tells these microglial cells, we're going to destroy your brain just because the gut changed because you took antacids or overused antibiotics or other types of drugs, nonsteroid anti-inflammatory drugs like ibuprofen.

Okay. So let's start with, okay, so let's start with the idea of this. So is there a test or a way that people can even know where they, how healthy their microglia, I can never pronounce it, microglia cells are? Like, is there, is there like some type of blood test for us to know where, where we are in terms of health?

Absolutely. One thing you can do is look at your calendar and ask yourself how old you are.

29.

There you go. Because microglia shift more aggressively the older we get.

Okay.

So that's a very powerful metric. The next thing you can do is—

what age do we start shifting?

It happens earlier than you think. It happens around 50.

Okay.

Aggressively. But it, you know, it happens in our 40s as well.

Okay.

It brings me to a very interesting point, and that is the paradigm under which we live right now related to brain degeneration is one that would say, wait until you become cognitively impaired. Think about your mother's experience and your experience with your mother. Nobody paid any attention to her brain till suddenly she started complaining about things and went to the doctor to say, hey, I forget—

No, that was just because she got very confused. But yes, until someone else recognized it.

That's very, very typical.

Yeah.

But why do we wait until then?

How old—

may I ask how old your mother is?

Well, now she's 83.

But when did those issues begin?

It started at 60. Honestly, like only a year and a half ago.

Okay.

2 years ago.

81 or 80.

Yeah. Is that normal? Is that a normal age for this?

My point is those issues began in her 40s and 50s. That's when the, the seeds are sown. So your audience needs to hear this, that the metabolic issues that will threaten your brain and presage the cognitive issues begin decades ahead of time.

See, I did, I, I did hear you talk about that, that they, they, that's been out there, but then what are the signs? Like, cuz you know, when people, a lot, we all kind of joke around like, oh, you know, like I'm in menopause, I'm in perimenopause. Oh, I have got like, you know, like I've got, people think that when they're forgetful or confus— or just kind of just mindless, it's like their situation or circumstance. It's not necessarily that. So how do you, how do you distinguish between if it's like decline of your cognitive functions or just circumstance?

Yeah, let's get back to, I think, the original question. Where do we get the sense that we're already setting the stage for brain decline? Your blood sugar starts to elevate, your fasting insulin level goes up, you're working too much that you can't get exercise, you have fragmented sleep, you're looking at your Apple Watch or your Oura Ring and you're seeing that you're not getting enough deep sleep, you are isolated. You're not spending time in nature. Your waist-to-hip ratio is increasing by a very sophisticated piece of machinery called a measuring tape. I mean, these are powerful indicators that your microglial cells are shifting.

You know, I'm noticing you're not wearing an Apple Watch, an Oura Ring, a Whoop, none of it. You're right. And is that— is that by design?

No, because I do. Oh, you do? I do wear a continuous glucose monitor.

You do? But I'm wearing a suit, so I can't see that part.

Oh, I'm not wearing it right now.

Okay.

But I do these things not all the time. You know, there's been some commentary that, well, can we get a little neurotic about it? And I find it's a little bit stressful for me, but I do want to know. So I wear my— I use an Oura Ring. I do it, you know, for several weeks at a time, every month or two. Same thing with CGMs. I have, you know, boxes of them at home. I work with Levels Health, so I get as many as I want. But here's the point. I mean, This continuous glucose monitor is powerfully informative for you, Jennifer, as an individual. What is your blood sugar doing in relation to the foods that you choose to eat in your relationship to your level of exercise, quality of sleep, relationships, time in nature, et cetera? You wouldn't know that if you don't measure. So you've gotta measure, and you can buy a CGM at Costco without a prescription. How wonderful is that? You know, It wasn't that long ago that there was an editorial in Journal of the American Medical Association saying, oh, there's a trend that people who are non-diabetic are wanting to get CGMs to learn about their blood sugar.

And the comment was in the editorial, we shouldn't allow that because people are going to become neurotic about their blood sugar. With that logic, we shouldn't allow people to buy bathroom scales because they'll be, they'll wonder what their body weight is. No, we should. Have the option of knowing these metrics.

Right. And taking the ownership in our own hands. Right. And having informed— like having informed information.

That's my mission in life.

Yeah.

Is giving people stewardship over their brain's destiny. Right now in America, we offload that stewardship to pharmaceutical companies with the hope that we can live our lives however we want and there'll be a magic drug drug to fix the problem. That situation is non-existent right now. I mentioned before, would I be supportive? Yep, you bet I would be. Yeah, that's my job, and I will put that drug in my toolbox, but we don't have it yet.

So, okay, so let's just stay on this for the— because you're like, what— that's a very, very good point. Like, you're— if someone is concerned about a lot of these, you know, diseases that can happen in the '70s, '80s, it starts 40, 30 years before that. And when you're confused between if it's just like circumstance, like menop— whatever, perimenopause, ki— children, stress, work, whatever it is that you're— and, or if it's something larger, some of the metrics are to check your blood, blood sugar levels. What was the other one? Says check your, your hip to your, your hip—

waist to hip ratio, your fasting insulin level, your A1C. And I think beginning at age 50, a little bit more sophisticated testing, one called p-Tau 217, very predictive of Alzheimer's. And I didn't know that when I submitted the manuscript for this book just several months ago, because that study came out 3 weeks ago in the Journal of the American Medical Association saying that this p-Tau 217 that we used previously as a diagnostic for somebody who's having cognitive decline to determine is it Alzheimer's is now demonstrated to be predictive predictive in terms of who's gonna get it. So that would be a great test to have. I just had mine done.

Where did you, where do people get that test?

Any lab could do it and you don't need a prescription. Walk into a Quest and say, I want a P-tau 217. They'll sit you down in the chair and they'll draw it.

Really?

You bet.

I think this is also, you know, Dr. Dale Breseden, is that?

Bredesen.

Bredesen. Very, very well. Right, okay. He was on here a while ago. I think he mentioned that test actually. Or a form, is there another version or form of that?

No, beta-2-17.

That's the one?

There are others that he talks about, GFAP, neurofilament light. Those are ones that he's very fond of, but he's correct. And the other thing that Dr. Bredesen talks about is he believes that once we reach a certain age, like 60 or 65, that we should have annual evaluations of our cognitive function. He calls it a cognoscopy, like a colonoscopy, he calls it cognoscopy.

How would we do that?

You can do them online now.

In fact, he has—

Oh, that's— web-based tools that allow you— we talk about him in the book. In fact, I feature him in the book, some of his case reports. And, you know, I so honor his work. And he is, you know, he takes a lot of criticism, and wrongly, I believe, because he is a trailblazer. One of his recent books I wrote the foreword to, and I talked about him in terms of a Nobel Prize, because not only the work that he's doing, But the idea that he challenged the idea of modern science looking at one variable to test something like a drug or a single intervention. As you know, his approach to dealing with Alzheimer's brings in multiple inroads, diet, nutrition, exercise, identification of toxins, for example, and even heavy metals, all the things that he talks about. And that is absolutely breaking the mold, and I'm grateful that he's done that because now we see new studies coming out where people are doing multiple things at one time and seeing great results and reversing Alzheimer's disease. Yes, it is happening right now without drugs.

I mean, how old are you? 70?

71.

71. And you're like sharp as a tack. Hopefully. Yeah, no, no, no, you are. 16 books later. What is your day-to-day? Like, what are the habits and rituals that you do daily to be so, like, that you're, that you're doing for 10 years from, like, you're probably, you're probably doing things that you'll be healthy for in your 80s or 90s. What can people glean from you? Yeah.

You know, people ask me this question a lot. Of course they would. I was thinking about this the other day, and one thing I haven't said that I will say today that I think is so important is, are two words, have Fun. Now, why do I say that? Because I think it's a question people should ask themselves. What do I do that I really enjoy that makes me smile? And I know the things that I do that make me smile, that bring joy to my heart. And that, I think it's a good question because that's really important for you to offload stress and to have a good time. The other thing is, you know, I think the real actionable levers that I pull, I exercise every single day. Are there days that I will— I will probably miss tomorrow because I have a 6:00 AM flight and I won't get home till probably 8:00 PM at night. But otherwise I exercise every day. Exercise is so important. Yeah. For your metabolism, for your waistline, for your body weight, all the things. You'll look good. You feel good. Brain loves it because your muscles, when they are activated, are secreting chemicals that do wonderful things for your metabolism.

Some of those chemicals go into your brain. And keep shop, you know, they do good things.

Talk about the BDNF, you know, I mean, of course you know what this is. It's like fertilizer for your brain in a way. I feel like the exercise to me, I mean, I'm not the doctor, but I think exercise is the number one thing that could keep it kind of keep these diseases at bay because what it does to your brain. Like I, for me, I work out, I mean, I don't work out for my, my physical well-being. Yeah, do I want to look good? Yes. But what it does to my brain— more focused, more alert. You have— your brain turns on with exercise.

So yeah, there are a lot of reasons for that. BDNF is one. So BDNF is brain-derived neurotrophic factor, and it is brain-derived. That's the BD. And I think that's an important point, that while muscles do create a very minimal amount of BDNF, they actually create a chemical when you're using your muscles, i.e., exercising, called irisin, and this irisin then able to cross the blood-brain barrier, and then within the brain stimulates the production of brain-derived neurotrophic factor that does a lot of different things. It nurtures the neurons, keeps them healthy and functional, but it also increases the growth of new brain cells. Who wouldn't want that? Why, that's fantastic. WTF, right? Why, that's fantastic.

Right? Yeah, I've never heard that one before, but yeah.

But it stimulates the growth of new brain cells, not throughout the brain, but in some very important areas like the hippocampus, the brain's memory center, the dentate gyrus of the hippocampus.

Can I ask you a question on that? Sure. Just before you move on, 'cause I know strength training's extremely important as you age for your bones and for falling and all the things. For your actual brain though, in terms of its, uh, workability, it's for it to be sharp and on the ball and all the thing alert. Is cardiovascular more important than strength training? 'Cause I feel when I do the cardio part, that's when my brain is triggered and turned on. That's the lever that I pull if I need to be on point. Do you— is that actually— is there science behind that?

Yes. And, and what you're saying, I think, is something many people experience. I think when your audience hears you say that, they're going to say, I feel the same way. Then what's all the push about strength training? Now, let's just wind back a little bit to our conversation from about 2 minutes ago, that the muscles are creating these chemicals that are doing good things for the brain in the long term, not the— in the acute sense, you're right about the aerobics. So, yeah, if you want more of those chemicals, then you need bigger muscles. So now you're gonna have a bigger resource to create the irisin and the interleukin-6 and the cathepsin D and all of the things that are good for amping up the brain function over the long term. Good. You want a bigger resource, so you can't forget leg day.

You're right.

Your leg muscles are the biggest ones. And you really, you're not doing leg muscles to look good. No one's really looking at your legs. Maybe they are. Everyone's doing triceps and biceps and pecs.

Of course. That's men. That's men.

Men. Okay.

Women are doing butt and legs.

Butt and legs. Well, butt is good because those glutes are pretty big muscles.

Big, the biggest muscle, the biggest muscle.

Well, hamstrings and quads as well. So you want to really emphasize, you know, your extensions and your squats. You want to really strengthen those upper leg muscles and calf muscles as well. Pecs are, are, can be big in some people, of course, but you don't want to, you don't want to forget leg day. Why? Uh, for all the other reasons, yes, and metabolism, of course. Metabolism targets your microglial cells, but just to have more of those great salubrious chemicals produced that make their way to the brain. They move, they're called myo, muscle, kine, they move, myokines move from the muscle to the brain. So the muscles are endocrine glands. No, I thought the endocrine glands were the pituitary, the adrenal, the thyroid. Because the, and the definition of an endocrine gland is an area in the body, a gland or an organ that produces chemicals that go elsewhere and target other organs and do things like the thyroid targets your brain and your muscles and everything else. And the muscles do that. They secrete chemicals that target the heart, that target the blood vessels, that target the pancreas, liver, and even, yes, the brain. So let's take full advantage of that.

And yeah, your muscles are making chemicals. I want more of those. Therefore I do strength training. So where does the rubber meet the road on answering your question? An interesting meta-analysis—means it looked at multiple studies, more than 30 studies—was published by Chinese researchers and tried to answer that question. What's better? Aerobics or resistance training. The conclusion that they came up with was both. So that's the recommendation. Not that I feel that's the right thing to do. Uh, that's what the science tells us. So aerobics, very important. You feel better, go for it. More of a cardiovascular blood supply kind of approach, more metabolic types of benefits are gonna come from the strength training and the added benefit of these chemicals that we talk about. This interleukin-6 that some would call an inflammatory cytokine, and it is, but at the same time, multipurpose, uh, this interleukin-6 increases something called AMP kinase. And what does AMP kinase do? That increases our ability to burn fat, increases the functionality of insulin. It's how the drug metformin works. So That's what, why we wanna build muscle and do both. Now I'm gonna add to that. The discussion's always aerobics versus strength training.

What should I do? And I think there's a third leg, even a fourth leg to this stool. And I would add, uh, that we need flexibility training because if you're not flexible and you overdo it at the gym one day, you're gonna hurt yourself. Then the exercise program comes to a crash. Uh, and if you're not, uh, working on balance training, then you run the risk of falling. And the older you get, you know, the higher that risk of falling, break a hip, then you're, you know, in women, hip fractures are associated with ultimately about a 40% risk of dying from that fracture over the long run. So you wanna work on your balance so that you're not at high risk for falling.

So balance, flexibility, and strength training and cardio. So the way I— Okay. So cardio is, but like you said, it is, it's more like in the moment cuz it turns on your brain, but you also, Talk about the metabolic piece of it, which is of course strength training will help with it, with your metabolism. That makes sense. And of course, so all 4. So you really can't get away with just like picking one. Basically it has to be all 4. All in. All in. Okay. So then finish what you're, okay. So I, I kind of cut you off. So you say you work out every day. How long do you work out? What time do you work out? I wanna know every detail.

So for me it's the morning, and I'm not saying that's what everyone should do.

What time do you wake up in the morning?

I wake up about 6:30. Okay. Does it matter? Sometimes 6. Well, I think when did you go to sleep?

Right. So my question is—

So I want to get about 8 hours of sleep, of good sleep. I want to measure my sleep and make sure I'm getting restorative sleep, uninterrupted sleep. And that's, I think, very important because people say, well, I slept 8 hours last night. Oh, great. How many times did you wake up? Well, I don't think I woke up at all last night. How would you know? Because you can almost wake up and not fully wake up to the extent that you don't remember it, but you really dropped out of sleeping. And your Oura Ring is going to tell you that, or your Apple Watch will tell you that. So I think it's, it's valuable to know that, and you, you could fix that. It might be that if you have a partner, that that person is snoring or moving around at night or got up 3 times to pee and woke you up in the process. So it's that valuable that you might need to make some adjustments in the sleeping arrangements. I was just interviewed about this idea called sleeping divorce, getting a sleeping divorce. What it's a kind of aggressive moniker. But if you can't sleep with an individual and have a wonderful marriage or whatever the situation is, by all means, if you have the opportunity to go to a different room or put a bolster between you or figure it out, play some white noise in the background if that person's snoring and keeping you up.

You spend a third of your life, or you should, sleeping 8 hours of a 24-hour period. You don't exercise or you you probably shouldn't for 8 hours a day, or eat for 8 hours a day, right? Or do brain training exercises. But sleep, you know, we used to think, oh, that's when we're taking time off. No, it's a valuable recovery period for consolidation of your memories, for activating your lymphatic system to take out the garbage, allowing your brain to have the optimal internal milieu or environment so that you don't stimulate your brain's immune cells to shift to being the evil twin.

You know, I feel like again, like things have its ebb and flow and trends. Sleep has become like the new kale.

You know, everybody, you know, I still love my kale.

You still love your kale. Good. Me too. I like kale, but I, or cauliflower. I feel like right now it's like everyone's on the sleep bandwagon. No one talked about it 10 years ago. Now everyone's talking about sleep being the number one thing. It's like the panacea for everything, you know, to be more fit, sleep more, to be more, to be smarter, sleep more, to like, you know, do whatever it is, it's about sleep. Now, why now? Like, why has nobody again talked about the importance of sleep? Well, I think it's because now it's like a trillion-dollar— well, now it's like a trillion-dollar business.

Of course it is. And, and I think it should be because it's taking us away from the idea that popping a particular supplement or deciding to push the limits and take a certain drug is going to be the answer. You know, it turns out back to lifestyle. I think that Morton Walker's book— Matt Walker. Matt Walker's book, Why We Sleep, really, I mean, it was a big hit, really raised our awareness. I think that, you know, looking at this whole science of chronobiology and the great research Satchin Panda is doing and getting out to the public really answers a lot of questions for us about why we're failing. And, you know, this notion of sleep being downtime, it's anything but downtime. When you characterize sleep as being downtime, it sort of makes you feel like it threatens your productivity. Mm-hmm. I was gonna say that. Because I could have been doing something. I could have stayed up till midnight and really gotten a little bit more done. The answer to that is no, you are more productive when you get a good night's sleep. Especially important for young people to understand this. Yeah. You know, kids in high school and in college, You know, cramming for the test, staying up really late.

No, get to bed and consolidate those memories. You'll remember them. You've studied once. Go to bed. Let those memories, you know, get more inculcated into networks. That's the ticket. And, you know, from my perspective, when we look at the relationships between not getting enough restorative sleep and risk for Alzheimer's, risk for diabetes, risk for obesity, which contributes to Alzheimer's risk. Boy, it is an incredible tonic. And I don't think this is gonna be a flash in the pan. You know, various types of supplements that we talk about, you know, come and go. A million.

Yeah. I mean, there's a million of them. Yeah. But this has become such a big business now. So it's only, only be food, like people are jumping on the bandwagon because they can make a lot of money from it. But also, 'cause it's something we all do anyway, right? Like it's pretty brilliant, right? We all sleep at least 6, 7, 5, whatever hours a day. Can't get away from it. We all eat. Right? So it's one of the— it's like the one most basic function that we do. So the thing is, and everyone— I mean, I just find it interesting that everyone now is like, sleep, sleep, sleep, sleep, sleep.

No, sleep isn't the only way. Sleep, exercise, and what we eat. Yeah. Because as you just said, it's things that we are already doing. It's basic. Well, we may not be taking rapamycin, or we may not be taking, you know, metformin and these things that have their moment of— in the sunshine. Yeah. And then, And then the other things come out that indicate, well, you know, there's no real data here that indicates what is what we should be doing. Right. So it remains interesting. You know, we look at the GLP-1s, for example, man, that's having its moment in the sun. Oh. But we don't know what's going to happen in the long term. And, you know, I talk about it in Brain Defenders because you, I think, insinuated earlier that this is an intervention that has huge and positive metabolic effects, huge and positive metabolic effects that relate to things like mitochondrial function and blood sugar function.

I wanna talk about that actually. In fact, I'm still, we still don't even have all your habits. Okay. I keep interrupting you. So far you sleep 8 hours, you work out every day, 6:30 you wake up. Tell me what else and then we're gonna move on.

I don't have lunch or even breakfast oftentimes. Well, which is breakfast, 'cause you're, you know, day you're—

You don't eat breakfast. Are you inter— You're breaking break fast.

So I do have breakfast, but it may be at 1 or 2 in the afternoon. It's more like lunch. Yeah, well, but you're breaking your fast.

So are you— so you intermittent fast?

That is by definition, you know, that's time-restricted eating, which is a form of fasting. But these terms are tough to define. What is intermittent fasting? Uh, how often do you do that? And what is the time period that characterizes that definition? I don't know, but that is something I do with, with regularity. So, okay.

So, 'cause you also talk about fast mimicking diet, I believe, in there too. Yes. Uh, Walter Longo.

Walter Longo. Another— putting out some really powerful research. You know, a lot of his work, though he's recently published on Alzheimer's, a lot of his work has looked at the idea of increasing ketones in the body as an adjunctive way of treating cancer along with standard approaches to treating cancer. And by all means, he's certainly not the first person to, to recognize that cancer cells thrive in a sugar-rich environment. Reducing blood sugar, getting it under control, and powering the body with ketones has been looked upon by not just, uh, Valter Longo, but many others, uh, as an adjunctive therapy to go along, uh, in with treatment of cancer.

So is it just overall eat less? It doesn't matter what the name, it doesn't matter if it's intermittent fasting, fast mimicking diet. If it's this or that, the other, the thing is it's about eating less. Yes.

And what you may consider to be trendy, but I think is here to stay, is eat more fat. I mean, these lips uttered those three words. And, you know, there was a time that I wouldn't say that my medical license would have been yanked, but, you know, I wouldn't say that to my colleagues because, oh, but all the data says a high-fat diet can cause your children to be born naked or some horrible thing is going to happen. Back in the day. Everything was low-fat Oreos, you name it.

And yeah, I remember SnackWell's and all the things.

Yeah, low-fat because of course fat is the enemy. Let's nuance that a bit, that I am not saying eat all fat, that all fat is good. We want to characterize those fats as being the right kinds of healthful fats, not highly modified fats that are devoid of healing potential. So these are not the fats that have a shelf life of months to years, or the fats have been modified that they can go into these ultra-processed foods processed foods that have an extended shelf life. We want to avoid those, of course. But wonderful fatty foods like avocado, nuts, fish, shellfish, these are providing to us fats that the body, not just the brain, the brain desperately needs fats. Of course, your brain is 70% fat, dry weight. I'm not accusing you of having, of being a fathead. Your brain is made from fat. The membranes covering every cell in your body, not just the neurons, are made of fat. It doesn't come from the air we breathe, it comes from the food that we eat.

Okay, I'm not going to interrupt again. So, so I've interrupted. Exactly. Okay, we both have. Okay, so 6:30 or so you wake up. What time do you go to bed at night?

9:30, 10? 9, 9:30, uh, sometimes even earlier depending, uh, on, uh, you know, if I'm tired I go to sleep and I don't have any trouble going to sleep, but my wife, uh, if there's computer time or television time, we'll have a lot of trouble. So it's either the blue light glasses or we just don't do it at night. So, you know, read, read before you go to sleep. That works for us. Or talk. Talk. Who knew? Exactly.

Talking, that's so archaic. I know.

Okay, so you wake up. It's the best though. I still look forward to it. Yeah. Just the goofy things happen that happened during the day. And we're both trying to figure out life. What does it mean? What should we be doing with parents? How do we raise our children? How old are your kids, by the way? 38 and 36. Wow.

Okay. You're not raising them anymore. I guess they've already raised— No, it never ends. But is your son a doctor as well? Right? Yes. So your dad was a doctor. Your son's a doctor. Correct. Does he have a child?

2 weeks.

Oh, really? Oh, wow. So what type of doctor is your son? He is internal medicine.

Okay. And, uh, but he is running a startup company and running the science research part of startup company called Big Bold Health that is involved in something called Himalayan tartary buckwheat. You may have heard. Yeah, I have. Powerful polyphenol. He works along with a fellow by the name of Jeffrey Bland. Yes.

Oh my gosh, I know that's— your son works with him? Yeah. Oh, that's such a— did he— did they get introduced through you? Probably.

Well, the Blands and the Perlmutter have been friends for 35 years. Okay. Yeah. So Jeff Bland knew Austin when he was 5 and 6 years old. A baby.

Yeah, yeah, yeah.

We would spend time each summer together in British Columbia. So— Really nice. Yeah.

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Digression is totally cool.

Okay, I'm digressing a lot here with you. Okay, good. I feel— I'm like, I'm gonna get like in the comments, stop interrupting him.

Okay, we're interrupting each other, you guys. That's what conversation is called. It's very respectful too.

Thank you. Okay, so, but I am very curious because I want to jot down what you're doing. So you wake up at 6:30, you don't eat breakfast. So what do you go right into the gym?

Like, what do you Generally, I get my exercise done in the morning. And so what do I do? No, not that early. No, I don't. Well, I mean, my exercise begins often around, depending on what my schedule is like, but it could be 8 o'clock. Okay.

Do you drink coffee in the morning?

I do drink coffee in the morning. And some may say that that is a violation of the time-restricted eating, but I am here to say it's a ritual. I love it. I feel great. I recognize— here's the self-selling— that it is rich in polyphenols, that caffeine is good for me. And so I'm more than an aficionado. I am a devotee. And then— What kind of coffee do you drink? I drink Purity Coffee, as a matter of fact.

Okay. What do you put in the coffee?

Generally nothing, or I might use some whole milk, which is another violation of the time-restricted eating. I won't tell anyone. For the past, well, my life is an open book. Yeah, I'm teasing. And I often use allulose.

Oh, okay.

So I'm very, very big proponent of allulose. Then what is actually—

You should try these, these are really good.

I'm going to try one. I could try during the show.

You know, I forgot to do them, but they're basically, this one actually is no caffeine. This is Magic Mind, by the way. You guys have all heard me yam around about this.

Ashwagandha, right?

Ashwagandha, lion's mane, Lion's mane. Yeah, all the things. They're very good. I'm surprised you don't know about this.

Well, we just met today. I know. So we've got a lot of ground to cover.

We've got a lot of ground to cover. My gosh, these are delicious. They're really— this is what I do before I work out, actually. It's like, keeps me focused.

So my program then, I have gym equipment at home and I have a new piece of equipment, which is a stationary bike called an Avalon, which gamifies, which is great because my mind goes elsewhere. But I frequently go to the gym.

Wait, is it the bike that's like, it's like an AI bike? Oh, no.

It's just gamified. And I'm online with other people. But then I also go to a gym that's nearby that is run by the hospital. And I'm, believe it or not, one of the younger people there. Really? Maybe I just think that, but it's, yeah, a lot of people in my generation there.

Do you do cardio or strength training?

Well, I do all of it. So my cardio is, and I run outside too, but in the gym, my cardio— You run? I do run. Yeah.

What do you say? Because, you know, there's like a whole blasphemy now because I like to run too, but like, so terrible for your knees and your joints.

And like, actually, that's not what the data shows. The data shows pretty good preservation of knee and cartilage with running. Now you can overdo it.

Well, I think it's endurance runners. Yeah.

I mean, I did my share of that. Yeah. And, um, but so I've taken— not to take it to you, but for the past probably decade, I've done elliptical machine. At home I have a Precor and I use that machine at the gym as well. So that is a zero impact way of cardio. How much cardio? I'll do that for 30 to 45 minutes with interval training, and which is great because you get— you see the graph. And also when you do your interval, you see the, you know, the curve come up. And I post that so people can see this is what interval training looks like graphically, right? So kind of hard to post while you're on it, but figure it out, right?

Yeah, yeah, yeah.

And so I really like that. And then I use a lot of weight machines, some free weights. And then when we travel, as I mentioned before we went on, we live on a boat for 4 months. On the boat I have bands, tension bands, a stepping machine, and then I use TRX, which I'm sure many of your audience is familiar with. I love TRX. Yeah.

So you mean a StairMaster?

A stepper machine. It's not a StairMaster, it's a little stepper machine.

Oh, just like, just like Yeah. Is that enough?

Oh yeah. It's not a stairmill. No, no. It's a stepping machine, but I can actually run the boat while I'm on that machine. So I can get up on what's called the flybridge and I can run the boat with a remote control. Our boat is really slow, so I'm not gonna hit anything. And I could be on that machine while we're doing that. And then we get off the boat and hike virtually every single day. Oh, okay. And we're in nature and we forage for mushrooms So we, we do that as often as we can.

That's great. Okay. So basically you exercise every day. Is there any foods that you are like, you are just, just, just addicted to that you have to have every single day? No. Okay.

But you know, I have my, we love salmon because we catch fish all summer and we are generally able to freeze enough salmon to keep us throughout the year, the rest of the year when we're off school. Oh, wow. Okay. Yeah. So I think salmon's a great food. I love it. I love to catch the fish. I love the DHA content and I love the assured cleanliness of knowing that it's wild salmon 'cause I caught it. Wow, yeah. Yeah, so I know that. For whatever reason, I could probably find a way of arguing my way into this. I love onions. I love the cruciferous vegetables. I sprout broccoli seeds at home and I'm doing it on boat as well.

That's a big one too. There's like, that's huge. Broccoli, like the sprouted broccoli sprouts are supposed to be amazing for your brain.

Well, it's amazing throughout the body. The, I think the really the go-to person is a fellow by the name of Dr. Jed Fahey. He is the, probably the world's authority on sulforaphane. And sulforaphane is that chemical that is created when we chew the broccoli sprouts. The broccoli sprouts are rich in something called glucoraphanin. And when you chew broccoli sprouts, the glucoraphanin in the presence of an enzyme called myrosinase that's liberated by chewing converts the glucoraphanin into into sulforaphane. This sulforaphane then activates a pathway in your body called the NRF2 pathway that is hugely antioxidant, that is hugely involved in detoxification, and powerfully anti-inflammatory. So that is the home run that you're looking for. Dr. Fahey, Fahey, just published a new report on the effects of sulforaphane on the brain and the research is profound. And I've only had him on my podcast, and I will meet him in February. I invite him to be a guest at Integrative Healthcare Symposium as one of our speakers. So I can't wait to meet him face to face.

Is this your, is this your symposium? Is this your thing, this integrative?

I am the health, I am the chairman of that symposium, but this will be my first year as chairman. Oh, okay. But I've been speaking there for 25 years. Wow.

How big is the this symposium?

Uh, it'll have probably 800 people as in attendees.

Yeah.

What kind of doctors is everybody goes? That's— it's integrative. That's all we want. So plenty of MDs, DOs, chiropractors, other healthcare practitioners like dietitians, acupuncturists, body workers, you name it. Really?

Okay, maybe I'll go.

Let me ask you now, when is it? It's in February, and I'll make sure you get invited.

I would love to. I'd love to go and see what—

it's in New York City. Yeah. Oh, every year at the same Midtown Hilton. Really? Yeah. And it's 25 years.

Who's speaking this year? Let's see.

One of our guest speakers who hasn't spoken there before is Dr. Li-Huei Tsai. And if she's watching this, she'll understand why I invited her. Because Dr. Li-Huei Tsai is at MIT, and she has discovered that flashing a light into your eyes at 40 times per second, so we call it 40-hertz light, actually targets your brain's microglial cells and helps revert them back to being supportive. So she's in the book and, you know, what can I say? Being chairman, I get to sort of influence who gets to speak there. Yes, you do. Yeah, that's true. So, you know, and there are a lot of wonderful other—

That's really interesting though.

Oh, it's breathtaking. And, you know, her work extends to humans, to Alzheimer's patients, the findings that she is getting. You know, our main topic today of discussion is how do we preserve the function of the brain's immune cells to be supportive by making lifestyle choices. But what we talk about is that this is where leading-edge neuroscience is exploring right now. So here is MIT looking at reverting the microglial cells to being supportive using A light flashing in your eyes at 40 times per second.

How does that work even?

I guess I can ask her. How does it work? Okay, you'll have to ask her, but I'll tell you. Yeah, tell me. So what Dr. Tsai made very clear is that the healthy brain has a beautiful background rhythm called gamma oscillation, a beautiful sinusoidal curve that is the orchestra playing a symphony. As the brain begins to degenerate, that gamma rhythm deteriorates and it's cacophony or every instrument playing a different thing. No more music. And what she found was that when we have good gamma oscillation in the background of the brain's activity, that the microglia are being preserved in their function and being kept in their supportive role. She discovered that when you expose the visual center and the back of the brain where vision is represented, the occipital lobe, to this particular frequency, that gamma is restored. Can you imagine? So they do at her laboratory, the Picower Institute at MIT. They put EEG leads on a person's head, and they discovered that flashing lights at different frequencies does different things. They tuned it in, and right at 40 Hz, gamma is restored. So people can then—

how do people do that at home? Is there a way you can?

I have a box next to my computer screen and it's always on while I'm working and I'm constantly getting 40 Hz light flashing in them. You can buy a light bulb.

So, you know, it's interesting. This is like the, you know, like this is kind of like the, the pink, not pink elephant in the room, but something like that. Like you're leaving the, you're burying the lead. This is like something that anyone can, anybody can do to prevent or reverse any type of immune cell deficiency that would lead to all these these terrible diseases.

It's a definite lever that you can pull. So, so we've talked about, yeah, training our muscles, strength training, aerobics, diet, metabolic— that's— we talked about that, how to do metabolic.

Look at this.

Dare I call it a hack? I don't want to call it a hack.

I'm not so keen. A tool. A tool.

A lever to pull. A lever to pull. Okay. And there's a lot of other cool things that are being developed right now.

I mean, I want to talk about other things that people can do. I— we talked about, of course, the Well, we haven't really talked about the mitochondrial health. Like, what does that mean to people? Like, how do people really have a strong— like, explain to people, or just to me, and then people can hear about the mitochondria, how we can— what we can do to have a stronger or more functioning mitochondria, because that also is something you talk about in the book.

So the question is then, why? Why do we even care about our mitochondria? What— why does it matter? Yes, tell us. Because it is the fundamental that determines the shift of these microglial cells. It's the failure of their mitochondria, their metabolism— mitochondria— that dictates friend or foe. Is mitochondria metabolism one of the same? Yeah, metabolism is, by definition, it's the creation of new materials from raw material. But it also, from a cellular perspective, But most importantly for our discussion, it's the formation of energy molecules from substrate. How do the mitochondria create ATP molecules from glucose?

The reason I'm asking is because we people— I've, I've heard a lot. People are very confused, right? They hear a lot of these buzzwords. They hear metabolic health, they hear mitochondria, they hear, you know, the, the gut, all about the gut, the how the gut That's the new brain. Like there's all these like very buzzy social media things that people, cellular health, but nobody really knows and understands what this means. I mean, they pretend because they hear it so often that you think that you understand. So I thought since you're such a nov— you know, you know so much about all of this is what you do. Like I wanted to kind of like really break it down, like what it means to have, you know, to work, to have like, to, for your metabolic health, what it, for your, to have this your cellular health? Is it the same? Is it not? Like, what can people do? Is there like a very— is there like a, uh, like a kind of like a, like a cheat sheet of how we can strengthen and improve all of these things to improve our ability, or to, to improve our health, but also to like, uh, help us not get these diseases later on?

I guess the answer is one 100%. That's why I'm here today. That's why we're having this discussion. Because again, there's no fix when you get into this problem from a pharmaceutical perspective, and it doesn't have to be. It isn't a genetic issue by and large. It's related to our metabolism. I'm gonna break that down. That's what you want. And we can control that. That's, that's what we're doing here today. Right.

But simple. I want it as simple as possible so people can take it like an actionable cheat sheet and be like, okay, let me, let me pave the way.

And then we'll talk about the actionable points. Okay. So again, we just kind of opened the door on mitochondria, the energy producers of the neuron. Wow, the neurons are very busy. They're sending electricity, connecting the networks, allowing us to think and do, right? That's what the neurons do. But the neurons are only 50% of the cells in your brain. We tend to think, oh, the brain is just a box of neurons. That's not correct. When we talk about brain cells, oh, you mean neurons? Well, no, we're having a different discussion today. We're talking about some other brain cells, in this case, 10% of the brain cells, the brain immune cells called microglia. There are other brain cells called oligodendroglia sites and astrocytes. We're focused on the brain's immune cells and their metabolism. Their metabolism, how their mitochondria are working, creating these energy molecules or not, determines whether they're going to be destructive and destroy your brain, as we see in Alzheimer's and Parkinson's and all the neurodegenerative conditions, or they're going to support your brain such that when you're 80 and I'm really old, we're going to come back and have another podcast and it'll be lucid.

Okay. Okay. How about— so like people, like, you know, the rage is NAD+, right? People think that's when they think of how mitochondrial health, cellular health, metabolic health. Everyone is injecting NAD+ or they're, or, you know, taking a precursor. Does that actually improve improve your ability for it? And they take it because of aging. They want to age better. That's the whole idea. They want to pro-age or whatever you want to call it. Does it actually make a difference?

Well, I think as it relates to oral precursors like NMN and nicotinamide— NMN or that?

No, NR is the way I—

Nicotinamide riboside or nicotinamide mononucleotide. I'd like to see the data to answer your question. I have not seen it yet. Then we move to the intravenous forms, which people rave about. Yeah. Because there is an indication that we can raise certainly blood levels and certainly tissue levels with IV NAD+. Yeah. But the question is, is there a payoff in terms of cognitive function, preservation of cognitive function, and even improvement? I haven't seen that data, but do I think that it makes sense? It does make sense when we recognize what NAD+ does, both in terms of mitochondrial function— makes sense to try to keep NAD+ levels higher, decline as we age, we know that— and the role of NAD+ in terms of influencing the sirtuin genes. I think on both counts it makes sense that we should do whatever we can to increase NAD+. That's why we exercise. So I think that we still need to see the research that relates the oral precursors to their ability to carry out these goals. That said, a recent study by Sinclair and Johnson looked at epigenetic clocks, age-related clocks, in terms of using a precursor, for example, and did not find any significant ability of the precursor to influence our biological age.

Interestingly, one of the best things that they discovered to reduce biological rate of aging, what's called the Dunedin Clock, I think was the mark when the metric was physical exercise. It's there for all, and it's free of charge, right? You got to buy a new pair of running shoes or whatever it may be, maybe from time to time. Uh, so, but I think we're going to watch this evolve. NAD is such a fundamental molecule in the functioning adequately of our mitochondria. To me, everything is about the mitochondria. Mitochondria. Why? Because the mitochondria are determining the function of our microglial cells. That's upstream for how the good brain continues to function or the bad brain manifests. It's the function of the microglia, which are determined by how their mitochondria are functioning.

So if the— if, if you say in the book, like many times, Brain Defenders, that the, uh, how your mitochondria is functioning is a correlation of your brain health.

Yes, absolutely. So, absolutely.

So if NAD helps the mitochondria, it would make that— there is a direct correlation. You're right.

It would make sense. Do I think it does? I do. Do I see compelling science to indicate that at this time? I do not. So, okay, my emotional response is supportive.

Okay. But there's— there hasn't ever— there hasn't been any type of science to back it up. Although I wouldn't say any type, because I mean, I know that I even know, like, you know, seriously, TruNiagen has done a million case studies for NR. Doesn't that count?

It counts. But I want, you know, what you're asking though, is there science that shows that taking a particular NAD precursor is going to benefit brain function? There's some indication that it might. But it's not the solid home run that I'm looking for to be able to respond to your question that way. Now, do I think emotionally that this makes sense to take some of this? Yes, I do.

Okay, or even any type of, even the IV or whatever? My sense is yes.

My sense is yes, but I have to do better. I have to delineate between my visceral response and what I do for myself based upon that and recommend versus what does the science support. So, and that's what you want me to do.

You're trying to be, you're just trying to be, you're just, I understand. You don't want to be in a situation where you're saying something out of turn without having the evidence to back it up.

Yeah, out of turn is well characterized. And the term here is, my sense is yes, but I want to be able to quote the study that shows that this is a powerful inroad to Alzheimer's prevention or even, dare I say, treatment. And not quite there yet. I understand.

What about oral health? I heard you— not I heard, it's in your book that what, brushing your teeth can starve away any type of brain decline. Is that the correlation? Well, I wouldn't say any type of brain decline. Well, no, but I'm saying you're giving all these things. You're talking about genetic testing, you talk about metabolic health, you talk about— there's a whole chapter on oral health that I saw. There's also a So two tests that you— that doctors don't tell you about, right? You talk about that, the homocysteine test. And what was the other one? And the fasting— and was it the fasting insulin test? These are things that I think are like— these are all part of the cheat sheet, in my opinion.

Yeah, I'll answer both of those questions more, but I want to tell you, this is a great interview, BTW. Really? It really is, because we're just going to what really matters. Yes. I mean, I think the mission here is to give your audience The Cheat Sheet or whatever are the tools, and you keep teeing it up. So I want you to know I appreciate that. Thank you so much.

I appreciate that. I do. I try. I like to get to the meat of the matter. I like to, like, no BS. I like just to know the facts and giving people actionable things that they can do, you know? And then so that's why, like, I know we kind of like digress and we go on these tangents, but I— because I'm a very curious person and I— when I have someone like you who's like who's very knowledgeable, I wanna like, I wanna kind of get as much, I wanna extract as much possible information from you.

And we only have 2 and a half hours more to go, so we better step up the pace. Exactly, exactly.

I know, chop chop.

So let me get to the first question first, which was the oral health. Yeah. And it's a bit of a surprise. I mean, years ago I wrote a book called "Brain Maker" that said, you know, there's a connection between the gut and the brain. Well, who knew, right? Well, Hippocrates knew, but more recently it was looked, are you kidding me? I'm a gastroenterologist.

What year did you write that one?

That came out, I guess, 12 years ago.

See, this is what I'm saying. And now it's become like, the thing. Everyone's just talking about it. Like it's been, so you were, that's what I'm saying. You were like writing about this stuff before it became like cool and trendy.

I didn't want it to become, yeah, trendy I went with. Cool was, no, I like iconoclastic because I always wanna be, you know, Or irreverent. On the edge. Irreverent. I love that word. I'm gonna take that from you. You can, just give me the credit.

I will credit you, okay.

I'm going to go on the hashtag. Okay, thank you. But the idea that oral health is important, we know that gut health is important and the digestive system is important for brain health. And who knew the mouth is part of the digestive system? This is where the tube begins and we know where the tube ends. Yeah. So it begins here. And the data that's coming out really relates very powerfully. Risk for Alzheimer's if you have periodontal disease goes up dramatically. I mean, to levels that you'd be, you know, you'd be surprised. We know that there are particular bacterial organisms that characterize periodontal disease that have been found in the brain, or at least parts of them, if not all the organism. Like a root canal?

If you have a root canal, that can lead to—

Well, more the periodontal disease, the area around your teeth being inflamed. Isn't that like a root canal? Bleeding. Well, the root canal is more the tooth itself and the root of the tooth.

I know you're not a dentist, but I'm just trying to like, you know.

Yeah, but, you know, not that there's not some concern about root canals. We could talk about that. About the idea that this gutta-percha that's used in the root canal can harbor bacteria. But let's go back to the periodontal disease, the gum disease, basically, that this correlation with perio— with heart disease and vascular disease and brain disease, all of which are inflammatory. But we're able to find this one organism, for example, that's getting a lot of attention that Dr. Bredesen brought to light called Porphyromonas gingivalis. That will not be on the quiz, but the idea that we find these organisms that are mouth-related organisms in the brain. So we begin to talk about something called the oral microbiome. Now with the same sort of skepticism and hopefully soon the same sort of appreciation that we previously applied to the gut microbiome, that the oral microbiome is important. I talked about it in Drop Acid, the book about uric acid. That's where our dietary nitrates from certain foods, uh, like beets, for example, get converted into nitrite that our body uses to make nitric oxide. Helps blood supply to the brain and organs and helps insulin do its job.

We don't want to sterilize the mouth. We don't want to be using mouthwashes that say kills 99.9% of germs. We love our germs. There are some germs that are bad in the mouth. I just mentioned one, but the idea of sterilizing the mouth once or twice a day with mouthwash You know, when I first heard this from somebody on my podcast, he said, you know, if you go to the gym and work out and then when you're getting your clothes on, you take a shot of mouthwash and spit it out, you've just offset the entire benefit of your workout. I saw that.

And I know what you're talking about.

And I heard him say that and I thought, well, you know, podcast, you gotta let people talk. And I thought, oh, how silly that is. Then I saw the research that came out. Oddly enough, from Puerto Rico, that demonstrated that people who frequently use a particular, particular types of mouthwash that sterilize the mouth, that we are all familiar with the brands, I will not mention them, that frequent use of mouthwash is associated with a significant increased risk of hypertension, as well as a significant increased risk for becoming a type 2 diabetic, both of which are powerful inroads to becoming an Alzheimer's patient. Person consider that. Is that really true? It's really what the science—

you actually saw the science on that?

I did see the science. When I first heard this, my surprise was what yours was, because I remember—

I, I know what you're talking about because I heard the same thing, and I was like, it's from the same guy who talks about this nitride— nitric oxide.

It is all about nitric oxide. I didn't hear it from him. Oh, you didn't?

I heard it from him, and I was like, what? I heard another podcast, and I was like, that sounds crazy to me.

I'm grateful this individual made this clear to me. And very close friend, his name's Max Lugavere. You probably have him on.

I know Max. Yeah, awesome friend of Max's.

When he told me this, I thought.

Maybe it was him who told me too, actually.

Yeah, and I. Could have been. I love that guy. I really do. I have so much respect for him. Yeah, he's very well known. I made him breakfast one day. We did some kind of live thing and he's great. I mean.

Yeah, he's great, yeah.

You know, he had a, you know, his situation with his mother. His mom, of course. Has done his best to help others not go through that. Yeah. God bless Max Lugaberry. No, I love— hey, Max. A genius life. Hey, Max. Yes.

And thank you for the t-shirt, by the way. Yes. I'm going to— I'm going to clip this for Max because— okay. We love you, Max. We love you, Max. So that's interesting. I— that— that whole mouthwash thing was very, very curious to me. So—

but it doesn't mean we shouldn't take care of our teeth. It means we absolutely should. How about a tongue scraper?

Is that why it's so popular? You bet. Tongue scraper.

Great idea. I travel with a water flosser. It's rechargeable, USB rechargeable water flosser. It broke 2 days ago. I immediately was at the— may I say the name? Walgreens yesterday and bought a new one.

That's really— so you even go that far? I was going to ask.

Oh, it fits in your— it's this tall.

It fits in your suitcase. No, I was going to say, so you're saying like just because I was going to say like flossing, a tongue scraper, You know, when you floss, you know, there's some that— like, this is like so random, but like if it's not a good kind of, uh, floss, you're not getting in there and getting all the good stuff out of there.

I floss, uh, but I don't like it. Yeah, I don't like flossing. I like sticking my fingers in my— yeah, it's weird. Yeah, my teeth doesn't work well, doesn't get everything. I love the water flosser, and I'm gonna get one of those. I mean, I use— it's a Waterpik, but not the kind that you have to plug in in your, in your bathroom at home. You can travel with this thing. USB rechargeable.

I mean, can you send me a link?

I'm gonna buy one. I will absolutely do that.

Yeah, no, I love that. I'm gonna— so, okay, water flosser, no mouthwash. I have been using the more healthy one. Is that a good— is that a good— healthy what? The mouthwash. I'm not using like—

I, I can't tell you because I don't know. If it has an antibacterial in it, I would think twice. Not— yeah, the, the bacteria that live on the top of your tongue are important because they're first step for your body to make nitric oxide. Nitric oxide, you need— it helps insulin work and helps your blood vessels expand to improve the blood supply to your brain.

Because, okay, so that's the part like I don't understand, but this nitric oxide, how does that fend off brain disease? I don't get the con— I don't get the connection.

I'm going to explain the connection for you and you'll get it. You'll never forget.

Okay.

Nitric oxide is important for metabolism, i.e., insulin functionality, blood pressure, blood supply. And metabolism, when it's not appropriate, is what threatens your microglial cells. That's the connection.

So why is that? Why people are putting it in toothpaste or they're putting it on in serums?

I don't think you're going to— you, you're not going to be able to put nitric oxide. They have—

I, I was just saying, but it's not nitric oxide, it's a precursor.

So usually things like arginine are put into toothpaste. And that's what more importantly is happening with toothpaste. The bad things are coming out of toothpaste, which is really good. There's all kinds of issues that have been in toothpaste for an awful long time. Sodium lauryl sulfate, which is, you know, is somewhat threatening certain of the sweeteners. So I'm glad to see that there's been a real effort, conscious effort, to create various brands of I use one called FYGG, F-Y-G-G, for your good guys. What does that mean? For your good guys means my mouth bacteria. I want to keep them healthy. They're on my side. They're along for the ride and this is their home.

Yeah. I mean, like people, like it's also these things that sometimes common sense isn't so common, right? Like it makes sense why that would make a difference, like your mouth, because that's where all these like living organisms are in your mouth. In your mouth, and if you have an infection, or it'll go into your brain, it makes perfect sense. Do you know they even said UTIs, like anything like these, why would a UTI?

Because a UTI is characterized by total body inflammation. When there's infection anywhere in your body, a urinary tract infection, lung infection, any infection in your body, those inflammatory chemicals called cytokines are increased in your body, and they make their way to the brain and they polarize our microglial cells away from being brain defenders to being brain destroyers. That's why it's important to, you know, we think about the quality of the water that we drink, right? You're drinking the water, you want to avoid water that might have chlorine in it, certainly microplastics and all of that. Right. But what about the air you breathe?

No one talks about that. Right. That's in the book too. You talk about that.

Right. You breathe 80,000 times a day. And we want to breathe clean, pure air without these PM2.5 particles that, you know, in the time of our discussion today, this is a time where wildfires are rampant in North America. I just came down from British Columbia. The air quality index is terrible. The sky is yellow and you can smell the smoke. That's why I stay indoors with an air purifier. And when I'm outdoors, at times I'll wear a mask because it's threatening to the brain. It's associated with an increased risk of Alzheimer's because it increases inflammation that is bad. Now, do people look at me in a funny way when I'm walking on the street with a mask? They might, but other people are doing it. Yeah, it makes sense. And I don't care. Yeah, you should. But I use, at home, even, we live in Florida, I have an air purifier. It's in our bedroom. We're breathing pure air. Called LichenAir, L-I-C-H-N. The lichens are these things in the forest that keep the air pure. So that's what we breathe. It measures the air quality. And you can get an app to look at the air quality index, the AQI, wherever you are.

We were recently in Cairo and the air quality index was mind-numbing. Literally, it was, you know, greater than 300. And I didn't want to go on these tours to the sites, the Sphinx and everything, but I did, and I wore a mask.

I guarantee you I wore a mask, and I wasn't alone. Yeah, well, again, it makes sense. So anything that brings the body inflammation. So at the end of the day, it sounds like inflammation is the core cause of any, really any disease at the end of the day.

It's certainly not the cause of trauma, but it is a fundamental player. It is a fundamental issue here. And upstream that we have to pay attention to is what is inflammation doing? What are toxins doing? What is elevated blood sugar and insulin resistance doing to our brain's immune cells? And what all these things are doing, and many more infections, are shifting our brain cells away from being supportive. And we want them to be on our side.

So what if you take a GLP-1 just for, not for your, not for weight loss, just for bringing the body's inflammation down. Does that work then, just for that? Is it strong enough? Is it true? Is there any real backed research?

To be fair to you, let me talk about the science first of all, and then I can shift to being speculative. And I want to clearly delineate between the two. Yeah. So if you accept that what makes a good brain go bad are changes in metabolism, metabolism, mitochondrial function, and how that plays out of the brain's immune cells. What if we were to target metabolism using a GLP-1 drug? It's a powerful way of targeting metabolism. So in 2024, in the New England Journal of Medicine, April of 2024, was a study that involved 151 patients who had diagnosed Parkinson's disease. It wasn't a question. They had Parkinson's. There were medications not doing well. Well, and it was a, a 1-year study that either treated them with placebo or an injection of a GLP-1 drug every day for the entire, uh, period. Now, the placebo patients basically didn't get treatment. What happened to them in the 1-year period of time? They declined in their functionality, as we see with Parkinson's. The group getting the GLP-1 agonist drug stabilized and actually demonstrated a tiny improvement. To me, that is—

when you say tiny, how tiny?

Well, the idea that they even stabilized, to me, is the home run. But even beyond that, they actually had slight improvement, which we've never ever seen, except for one study that we actually are— we carried out years ago using intravenous glutathione. But functionality improved by giving them a drug targeting their mitochondria.

So that's interesting because I heard that someone was telling me it was like a biohacker was telling me, oh yeah, I'm taking not the semiglutide one. They're taking either— was it retatrutide that works on the 3 receptors or the trizeptide 2, whatever. Yeah, that they're taking, they're microdosing it for to fend off Alzheimer's or dementia or any type of cognitive decline. Is there any accuracy at all to that then? Or is it just—

Mechanistically, first of all, I don't know what a microdose is in the context of this person.

Yeah, I mean, that's exactly a good— I know you can't say—

Yeah, I mean, I don't know what that means. I mean, what is microdosing of psilocybin? What is microdosing of DLP-1? I don't know, define the terms. But is there any science to support what I'm about to say? Or is there any science to support the idea that that's a good practice? No, there isn't. And we'll review what the science is in terms of Alzheimer's in just a moment, because recently there was a completed trial called the EVOKE and the EVOKE+ studies that were just completed that involved more than 3,000 individuals in over, I think, 500 institutions globally. Well, let me talk about that real quick. What did they find? This study did not reach therapeutic endpoint, meaning that the oral semaglutide did not demonstrate benefit in existing Alzheimer's patients. But interestingly, one of the findings that is not talked about is the fact that the C-reactive protein, a marker of inflammation, went down dramatically in the group receiving the drug by— so 30%. That's important. We don't know how that will play out. Could the study be refined? IV or rather subcutaneous injections, GLP-1, and a different GLP-1 that might make its way to the brain a little bit better.

Yes, I think so. We'll see where the science takes us. The idea of a GLP-1 being good for the brain, I think, has merit. And I actually mentioned it in the book. I, I'm keeping an open mind to the idea that some formulation of a GLP-1 may be good for the treatment of Alzheimer's in the future. Jennifer, Alzheimer's is an almost uniformly fatal condition. It is the third leading cause of death of of adults in America. And so the idea of using a drug that may have a side effect profile that may be helpful is something we have to keep our eyes open to. And I remain open to including it in the toolbox once we know which GLP-1, which formulation can we use, how safe it will be, and how efficacious it is. So I think it's very powerful. I think just the hit and miss trials of GLP-1, 'cause I think it's a good idea, I'm gonna microdose, not gonna tell you what the dosage is 'cause I'm not really sure, I vary from day to day. That's maybe interesting for an individual, but it's not science.

So you wouldn't take it? No. Are you on any GLP-1s? No. 'Cause do you, what do you think of the overall use of them? Do you think people are just like, just at this point, they're just, they're being abused by everybody? Do you think it's going to go away?

Do you think it's a trend? No, I think it's not a trend. Barring some demonstration of a significant side effect that's widespread, I think they're here to stay. And I, you know, because on the one hand, there's this huge effort to get people to eat crappy foods, these ultra-processed foods. That's not going away despite what we see the efforts being to make people aware of the GLP-1, I mean, of the ultra-processed foods. I'm one of those people people trying to raise awareness that consuming these foods is associated with Alzheimer's risk specifically, uh, and diabetes and obesity and all the things, uh, that's not going away. And therefore the GLP-1s will not go away. Are they completely safe? They are not. We don't know, uh, how many people are going to suddenly lose vision. By one report, as many as 30,000 people have lost vision acutely as a consequence of using these drugs. That's, that's a worrisome, you know, it's not a big number in comparison to the number of people who are using the drugs. So the incidence of that side effect seems to be low, but that's 30,000 people, no matter how you slice it.

They don't care about the others. So the idea though of targeting metabolism, I think is very important. And there may be supplements and drugs that are able to do that, that I will keep an open mind for. In the meanwhile, most of what we talk about are the lifestyle I don't want to call them hacks, but the tools— that was your term— that we've talked about today that do a hell of a job in targeting our metabolism, like getting enough sleep, restorative sleep, and exercising in both forms that we talked about, right? With the addition of balance and flexibility. Yes. And the type of foods we eat and connecting with other people.

Do you think it matters if you're a carnivore or plant— like a vegetarian? Do you think how much— but what about protein? Do you think protein's being over- over again, over now it's so trendy.

Protein is du jour, no question about it. And it's trendy. Did I have supplemental protein today? 'Cause I hope I get enough. Yes, I sure did. We'll get back to the question in a second.

You need some electrolytes after this interview.

Some lights. But I, you know, at my age, it's harder to maintain muscle mass. And that's a huge risk for all types of degenerative conditions. For injury, and for Alzheimer's as well. I mean, one of the most powerful risk markers for Alzheimer's is sarcopenia, loss of muscle mass. Yeah. And loss of grip strength because your muscles are weaker. So I'm doing everything I can to maintain muscle mass. And that means for me, making sure I get adequate amounts of protein, exercising a lot, like I've told you. And I happen to use a testosterone gel just to make sure that I'm as anabolic as I should be, not as I can be. You know, there are other things out there that I am not doing. I mean, there are gene therapies now that help you build muscle. I have not gone that. Am I thinking about it? I'm considering it, but I'm not really willing to accept that risk just yet. Let's wait for more data. Or peptides in general. Or peptides in general. I'm not using any peptides. Yeah. Would I in the future? Yes, but I want more data. You know, to me, it's really above all, do no harm.

And talking about me now. And so, yeah, yeah.

And well, it's interesting because when you talk to real— like, when I say real doctors, I mean real doctors. They don't want to be on a GLP-1. They don't put their, their wives or their husbands on GLP-1s. But for patients, it's okay, right? Oh, that's very common.

Do as I say, not as I do.

Exactly. Because there are risks. People don't— it's not trendy to talk about it. It's not something that is popular because people like, people are visual and it's like easy and, and it's like a quick fix. It is a quick, a lot of it could be a quick fix. You're getting these things from China. You don't know what's in your body. No one wanted to take a COVID shot. Remember like the, the conspiracy theories around taking, you know, the, the vaccine, but people are like shooting themselves up with 27 peptides. They don't know what those are. The hypocrisy is crazy. Yeah.

And I, I would say to a patient, friend who is asking me to go on a GLP-1 drug, let's just say for weight loss. Yeah. I would say, are you willing to commit to being on this drug for the rest of your life? Why did you ask me that, doctor? The reason I'm asking you that question is because when you stop, if you decide not— oh yeah, do that, and you're not going to be on the rest of your life, and now it's time to quit, chances are significant and most likely that you're going to gain back all your weight and then And that's where you're going to be when you decide you're not going to take this drug anymore. Now, that's a different conversation from the one I would have with the family and loved ones of an Alzheimer's patient if it were proven that this were an effective intervention. Right. Because we lack that right now. I would say that, you know, we're going to commit mom or dad to being on this drug because it does show significant efficacy, knowing that if we don't do it, that this is a fatal condition.

Yeah. So we have, you know, what do we have to lose? Right.

At that point, that's a whole different, that's a whole different ballgame. Okay. Talk about the two tests that people, that your doctors don't tell you about that could be very beneficial. Right.

To knowing where you're at. Neither of which requires a prescription. So you can go to your lab, ask them to do a homocysteine, H-O-M-O-C-Y-S-T-E-I-N-E. There's probably a graphic right now on the screen that says homocysteine. There it is. Magic. And so homocysteine is an amino acid that when it accumulates and reaches a higher level than normal, we'll talk about that in a moment, it increases the risk of Alzheimer's, cardiovascular disease, is threatening to the lining of blood vessels. It's a bad player in your body and it's simple as can be to fix. How do you lower homocysteine if it's elevated? You take a methylated B complex. Not just a B complex at the health food store, but one that says methylated B complex at the health food store, online, buy it. So you can get the blood test without a doctor and you can do the response without your doctor. And I put the parameters of where you want your homocysteine to be in the book. Now, there are genetic predispositions to having elevated homocysteine. I have that. It's called MTHFR. If you have it and you've got your genome sequenced, you've heard of MTHFR.

There's been mood disorders characterized by elev— by having MTHFR. The main thing for me is it causes me not to use regular B vitamins appropriately. So my homocysteine went up to 11. I took methylated B vitamins. I take them religiously. My homocysteine ranges between 6 and 8, so I'm okay. The other test, and we mentioned earlier, is a fasting insulin test that is predictive In terms of where your blood sugar's gonna go, where your A1C is going to go in the future. 'Cause the first thing that goes up is your insulin level. Then the blood sugar elevates, then your A1C elevates. So that's the great test to know where you are in terms of risk of that critically important metabolic marker, your blood sugar right now.

So how about the, you said something in the book, I don't remember exactly, mood disorders like anxiety, depression, does that cause inflammation in the brain, which then can also be a precursor for someone getting dementia or Alzheimer's?

So there's a profound relationship between mood disorders, primarily depression, but anxiety as well, and the presence of inflammation in the body. It is not to say that the mood disorder caused the inflammation. It is the opposite. It, that the inflammation leads to the feelings of depression, et cetera. When you are sick, you have inflammation in your body, you have the flu, you have COVID, how do you feel about interacting with other people? You don't. You don't want to be with other people. You feel crappy, you're weak. And it's because inflammation is actually changing your neurochemistry and leading to these changes in your mood. And that's probably good for the herd. Heard, right? That's probably good for all the rest of us that you decide you're going to isolate right now because you just don't feel like being around other people. You feel crappy. And so that might be why that happens. But to be sure, this is the inflammation that polarizes our brain's microglial cells away from being brain defenders to being brain destroyers. Again, we can image the human brain in living people to determine the state of function of our microglial cells. We can image the Alzheimer's brain and see that it's lit up on this special type of PET scan called a TSPO PET scan.

I talk about it in the book. It lights up with those microglial cells being shifted to their M1 configuration. But guess what? This TSPO imaging is positive in Alzheimer's. I mentioned that Parkinson's, MS, multisystem atrophy, progressive supranuclear palsy, PTSD, a major depressive disorder, long COVID, autism spectrum disorder, all of which are characterized by this activation of these microglial cells. Well, that's interesting from a research perspective, but it tells you and me something very important, that this is a huge net that is thrown, that if we can figure out how to rein in these microglial cells and bring them back to being supportive. That is a home run across so many, uh, areas.

Okay, I have a couple other questions. Random— not random. Don't stop, you're doing great. Thank you, thank you. There's a— what's that erectile dysfunction medication? It's not Viagra, but not Viagra. It's another one. Cialis. Cialis. I heard that Cialis is actually— people are taking Cialis to lower their, uh, risk for Alzheimer's. Is that, is that, does that actually work?

In an evaluation of more than several million medical records, a study was performed to determine, is there any indication that people taking any particular drug that might therefore, with crunching this data, would be associated with lower risk of Alzheimer's? It turned out to be these types of drugs. It turned out to be sildenafil in particular, which is Viagra. Viagra. Why would that be? It gets back to an earlier conversation we had that relates to the mouth organisms, nitric oxide. How do these erectile dysfunction drugs work? What is an erection? An erection is opening of blood vessels to allow the erection to happen. Blood fills the penis and it becomes— develops what's called turgor pressure. Turgor pressure is what makes it hard That's what an erection is. It's caused by blood supply increasing suddenly to the corpora cavernosa of the penis allows that to happen. It is a dependency upon nitric oxide allowing that dilatation to happen. That's why these drugs work. Now, nitric oxide improves blood supply, improves blood supply, as I mentioned earlier, throughout the brain, and nitric oxide improves improves insulin functionality for better utilization of glucose, keeping the blood glucose under control.

So is there evidence that these people are doing the right thing? Hard to say. There hasn't been an interventional trial that I'm aware of as yet. Do I think it has merit? I absolutely do.

So should we all go on Cialis or Viagra?

Well, I don't— I can't have the answer. You know, you want me to quote the science. That study hasn't been done yet. But is it mechanistically plausible that that is the right thing to do? The answer is yes.

So which one has more nitric oxide, Cialis or Viagra?

I don't have the answer for that. Okay. I think that Cialis is designed to have a longer half-life, so it might be a more appropriate choice than Viagra in terms of keeping that nitric oxide elevated for a longer period of time. But there's no data that I can quote to you right now that that's an appropriate choice. Okay.

So that's interesting. Okay. Mechanistically, it makes sense. Mechanic. Okay. The other one I have to ask you about is Benadryl. I heard not to take Benadryl because it does cause Alzheimer's.

Well, I'm not going to say that Benadryl causes Alzheimer's.

Taking it too often though can. Oh yeah.

I mean, but is there a ration relationship between taking diphenhydramine, which is what Benadryl chemical name is, frequently and risk? There is that relationship of risk. There's a, a, a bit of a, nuance— more than a nuance. I think it's important to delineate between saying that taking Benadryl is going to give you Alzheimer's to the idea that frequent use of diphenhydramine or Benadryl or Valium or anticholinergic drugs help you because you get up frequently at night to pee and risk for Alzheimer's. We know that's true, that risk is increased in men who take those types of drugs. Well, anticholinergic Block acetylcholine. Acetylcholine is a critically important neurotransmitter. That might be the reason. So that may be the reason. There may be other reasons.

But how much is considered too much? Like, can I take Benadryl once in a while?

If you take it once in a while, I cannot imagine that's a huge issue. We know that, for example, people who take antacids, these proton pump inhibiting antacids that are advertised on television where you see somebody tries to eat a sausage and And they get heartburn, they gotta take this PPI.

So anything, anything, when you overdo anything.

Yeah, but I mean, people don't think they're overdoing it because the messaging is take it every day and you won't have acid reflux or heartburn. And, you know, people who take those drugs every day do have a dramatic increased risk for Alzheimer's disease. That's published research.

I also heard Xanax, all these drugs, like all these anti— benzodiazepines. That's true as well, for sure.

But, but for me, so I see this data that relates taking these proton pump inhibitors.

I talk about it in the book. I know.

Why might that be? Well, these are drugs that block acid. They change the pH of your gastrointestinal system. What will that do? pH is tightly regulated, and the organisms that live there, that's the environment they like. All of a sudden you change changed the acidity and they don't like to live there anymore. They're gonna move, you know, it's too cold to live in Indianapolis. I'm gonna move to Fort Lauderdale. They don't wanna live here anymore and they're not there doing their job anymore. Right, right, right. So the, the microbiome has been one powerful explanation as to the association of nonsteroidal anti-inflammatory drugs with Alzheimer's risk and, uh, with these en— uh, anti-acid drugs as well. Certainly, and I talk about the book, antibiotic overusage is associated with dramatic changes in the microbiome and Alzheimer's risk. Please be clear. I'm not saying we should never take an antibiotic. They're lifesaving. They are wonderful.

But, you know, you can overdo anything though.

Well, the research indicates that about 50% of the antibiotics used in America are used inappropriately, and 80% of the antibiotics manufactured in America are used in animals that we eat. To make them fatter, right? Of course, 80% more than are used in humans.

That's why organic, I think, is obviously— that's why people don't want to eat regular, I guess, non-organic meat.

It's just breathtaking that we have to have a special effort. I know, to find foods that aren't covered in chemicals. And I talk about that in the book because I cover a lot. Well, look at those chickens at Costco.

Have you seen the size of those chickens?

I have. That's not normal. I know. And what stimulates their growth. Antibiotics.

Well, that's what I'm saying. Like, they're like, oh yeah, it's $5 a chicken. Yeah, but you're literally just eating a bunch of like antibiotics.

Get a bargain now on the chicken and you will be spending more money in the future dealing with your illness.

100%. Like, you pay now or you pay later. That's right. You know, I have one random other question for you. Were you ever, uh, like, because you've been writing books for 100 years, did you ever practice? Did you have like an act? Do you actually see patients now?

I don't now. I—

well, not now, but yeah, I practiced for 30 So you were actually, uh, like you were, I had, uh, you know, practice the largest integrative neurology clinic probably in the world. Oh, excuse me.

Yeah. For until when? Uh, until I retired, which was about 12 years, 13 years ago. So you were writing these books all and also practicing and raising kids and all the things. Oh, you were doing both coaching baseball, writing a book. Gimme a, yeah, it was, oh, I love that.

Oh, it was great. 'Cause I, 'cause the reason why I'm asking is so many times, and I say this a lot on the show, Like, you know, people are all like on the show as doctors, but they're not really doctors. They just play one on TV, literally. Like they're media doctors or social media doctors. Yeah. But they have, they don't see a patient. They're not really out there. 'Cause now they just want to, you know, be out there.

That, that's the reason I do what I do. Yeah. Now, 'cause I, I was in, you know, you were doing it all.

The one, you're seeing patients.

In the ER at night talking to the families saying, you know, what the outcome's going to be and wondering, why did that patient have to end up here? Couldn't we have prevented this? That's what I'm saying to myself. That's not the discussion you have in the ER at night. Blame, blame, blame. But why did the stroke happen? Why are there 800,000 strokes occurring in America right now? And then in my office practice, dealing with people who mom, dad, spouse is now cognitively impaired. I wasn't taught that in neurology training about what are the causes of the problem, only what prescription to write, end of story, out they go, done. That's not good enough. So I was not wanting to focus on the smoke, I wanted to focus on the fire. And I will say that having a father who died of Alzheimer's really solidified my dedication to this because patients would say to me, "You know, Doc, you just don't know how rough this is for our family." And I would say, As a matter of fact, I do. Been through it, you know? And I remember that the moment I realized my father had Alzheimer's, I couldn't imagine how I missed it for so long because I was a very good diagnostician.

I could diagnose Parkinson's across the parking lot, for crying out loud, and still do at the airport. And I go, "Oh, ladies and gentlemen." But I missed it with my own father until one day he He asked me a question from the bottom of the stairwell. He yelled up the stairwell and asked me this question. And I finally went, oh my goodness. Because we just talked about something the day before. Yeah, he didn't remember. And then I realized, and then everything else that he'd been doing made sense, but I did miss it, the diagnosis in him.

How old was he, by the way?

He was in his, he was about 84.

So he was also around my mom's age. He was older. That's right. And how long did it take? Like, what, when you noticed it, was he already, he was in a mild form, I guess, or?

It was very mild and it took years to progress. How long? And then at the end, uh, it took about 6, 7 years to really progress. But then at the end, it progressed very quickly as we generally see, you know, and, uh, that's why doing the things now with your mother are so important. Did I mention to you the study done by Rudolph Tanzi and Dean Ornish at Harvard? Again, let's revisit that. That was an interventional trial in patients who are diagnosed with Alzheimer's disease that in 70%, they either arrested their decline or even improved.

What do they do exactly? I'm going to send you the entire protocol because right now my mom's in that middle to advanced chance. Like, she's not like at the end yet. Like, she's now in a 24-hour care facility. She's very confused. Is it too late?

Nope, not at all.

You'll send me that stuff?

I will send you that stuff. As a matter of fact, we have it right outside.

You do? Yeah. Okay. And if— I mean, that'd be great. I would love to see it. Yeah. What else can we go over? It's been 100 years, but, uh, uh, let's let what we just talked about sit for us 100%, because this is why we do what we You can come back.

Well, that's all right, but you'll have another book pretty soon. Call it like it is, you're suffering. I know you are. And I've been there too. And it's so challenging because you're told there's nothing that can be done except for— and your mom tried the medicine, right?

She was on something that made her like very like agitated.

Yeah. So again, thank you for having this time together today because this is is, you know, I believe such a critical message. And I'm so glad that you've given me this opportunity to get it out there a little bit more.

Absolutely. I really enjoyed your book. I think your book is very— it's— there's so much in it. And even if people just like read a little bit, put it away, come back to it, like you really cover the gamut in it. And so I'm so glad that I finally got to meet you. Me too. Thank you for coming on the show. Really, the book Really, I'm really— I'm honored to have you here.

So I'm honored and grateful to be here. Thanks for this opportunity. Thank you.

And guys, pick up the book. It's called Brain Defenders. It's out now by David Perlmutter. And that's it. Have a good one. Bye.