The Dr. Hyman Show - Daily Hacks To Improve Your Health & Age Backwards

Episode Date: January 28, 2022

This episode is brought to you by Rupa Health, Athletic Greens, and Eight Sleep.   Aging doesn’t have to be a one-way street. Our diet and lifestyle patterns are fundamental to the quality of our health, and the way we age. In this episode, my guests and I explain how to support our health to help us live longer, and more vibrantly.   Dr. David Sinclair is a professor in the Department of Genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School, where he and his colleagues study longevity, aging, and how to slow its effects. Their focus is on studying sirtuins as well as metabolism, neurodegeneration, cancer, cellular reprogramming, and more.   Mark Sisson is the founder of the popular daily health blog, Mark’s Daily Apple, godfather to the Primal food and lifestyle movement, and New York Times bestselling author of The Keto Reset Diet and The Primal Blueprint. Mark launched Primal Kitchen, a real-food company that creates Primal/Paleo, keto, and Whole30-friendly kitchen staples.   Dr. Gerald Lemole is a board-certified cardiothoracic surgeon and integrative physician. In 1968, he was a member of the surgical team that performed the first successful heart transplant in the United States. His books include After Cancer Care, The Healing Diet, An Integrative Approach to Cardiac Care, Facing Facial Pain, and Lymph & Longevity: The Untapped Secret to Health.   Dr. Mehmet Oz has won ten Daytime Emmy® Awards for The Dr. Oz Show and is an Attending Physician at NY Presbyterian-Columbia Medical Center. Dr. Oz received his undergraduate degree from Harvard University and obtained a joint MD and MBA from the University of Pennsylvania School of Medicine and Wharton Business School. Dr. Oz is the proud author of eight New York Times bestsellers including his most recent, Food Can Fix It.   Dr. Cindy Geyer received her bachelor of science and her doctor of medicine degrees, with honors, from the Ohio State University. She completed residency in internal medicine at Strong Memorial Hospital in Rochester, N.Y. and is triple board certified in internal medicine, integrative medicine and lifestyle medicine.   Dr. Richard Isaacson serves as Director of the Center for Brain Health and Director of the Alzheimer’s Prevention Clinic (APC) at Florida Atlantic University’s Schmidt College of Medicine. He previously served as Director of the APC at the Weill Cornell Memory Disorders Program, Assistant Dean of Faculty Development, and Associate Professor of Neurology at Weill Cornell Medicine & NewYork-Presbyterian.   This episode is brought to you by Rupa Health, Athletic Greens, and Eight Sleep.   Rupa Health is a place for Functional Medicine practitioners to access more than 2,000 specialty lab tests from over 20 labs. You can check out a free live demo with a Q&A or create an account here.   Right now when you purchase AG1 from Athletic Greens, you will receive 10 free travel packs with your first purchase here.   Eight Sleep’s Pod Pro mattress is so smart that it adjusts your temperature and also gives you individualized recommendations on how to sleep better the next night. Save $150 at checkout and get yours here.

Coming up on this episode of The Doctor's Pharmacy. If you catch it early enough, and in the case of a mouse it was about the age equivalent of a 60-year-old, we could turn a 60-year-old equivalent mouse back to a 20, 30-year-old within a week. Within a week we could make old dysfunctional mitochondria function and appear exactly like a young animal's mitochondria in the muscle. Hey everyone, it's Dr. Mark. I know a lot of you out there are practitioners like me helping patients heal using real food and functional medicine as your framework for getting to the root cause. What's critical to understanding what each individual person and body needs is testing, which is why I'm excited to tell you about Rupa Health. Looking at hormones, organic acids, nutrient levels, inflammatory factors, gut bacteria,

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or create an account at rupahealth.com. That's r-u-p-a-health.com. I'm all about streamlining my daily health routine to be as powerful and yet simple as possible. And that's why I love AG1 from Athletic Greens. Because when it comes to my health, I want it all. I want my gut to function great, my brain to feel sharp, my immune system to be strong, my body to feel energized and able. And being in my line of work, I know that means I need optimal levels of nutrients, which is one scoop of AG1. I get 75 high quality vitamins, minerals, whole foods, sourced superfoods, probiotics, and adaptogens to support my entire body. Even with a really healthy diet, it's hard to hit the mark for all our nutrient needs. So I feel better knowing that

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Hi, this is Lauren Fee and one of the producers of The Doctor's Pharmacy podcast. Did you know we have two different ages? There's our chronological age and our biological age. Our chronological age is how old we are, whereas our biological age is the measurement of aging in our organs, muscles, and cells. Our biological age can be affected positively by making healthy lifestyle choices. And with the right steps, we can slow down and even sometimes reverse the aging process. In this compilation episode, Dr. Hyman talks to

Dr. David Sinclair, Mark Sisson, Dr. Gerald Lamolle, Dr. Mehmet Oz, Dr. Cindy Geyer, and Dr. Richard Isaacson about optimizing our health to feel better and live longer. Let's jump in. A large part of it is mitochondria. They do other things which we can touch on. They probably do a hundred things that we're still working on. Let's go back to yeast because I think that's a good framework. When we started in yeast we didn't know why they were dying. We figured that out. It's mainly genome instability that affects their cell identity, and then they die.

Discovering the sirtuins was a game changer because what we figured out was there are three levels to aging. There's the base level, which is the things that kill you, DNA damage, telomere shortening, mitochondrial dysfunction. That was pretty much worked out in the 90s. Then there was a level above that that there were these regulators of aging. The sirtuins are major regulators. But then in the 2000s, my lab and others found there was this top layer, which is the environment. And when the environment is a little bit harsh, adversity,

or even perceived adversity, it kicks these protectors into action. And then they slow down or reverse these causes of aging. So think of it as a hierarchy pyramid. So what you want to do is start at the top. So how do you trick the body into thinking that it's going to run out of food or that there's some other adversity? And we found in yeast cells, if you reduce the amount of sugar of sugar getting back to sugar they kicked into action the sirtuins um talk about how they did that in a minute and then the yeast cells lived longer they protected the dna they boosted mitochondria and they lived longer wait i just want to pause here so sugar you're saying accelerates

aging and restricting sugar actually helps increase longevity in these animals. Well, certainly for yeast and a lot of data on humans that lower sugar is better and fasting blood sugar is lower is better too for longevity. But there are other ways to kick the sirtuins into action. So there's in humans, intermittent fasting is easier, I find, than calorie restriction. I tried calorie restriction for a week. It was pretty hard. I met a guy once who said he's doing calorie restriction and he was a member of the calorie restriction society so what do you have for breakfast i have five pounds of celery

and three pounds of tomatoes and i'm like uh no thank you right well eating is one of life's pleasures um but i find uh for me, if I skip breakfast, it's no big deal. Yeah. So intermittent fasting is basically time restricted eating where you eat within a certain time window of eight hours or or 10 hours. Right. Yeah. There are plenty of varieties. I talk about them in the book.

There are some other books that talk about that. You mentioned this many times on your show. There are some skip a meal protocols that skip two days a week. There are some people, Peter Atiyah is doing skip a week of food. He says after three days, magical things happen, he thinks. I haven't tried that yet, but I'm going to. But yeah, no one knows actually what the optimal amount of fasting is. But what I can tell you is some time of being hungry is good.

We can see that in our animals, there's no question. If we give our animals, our mice, food every other day, they live longer. And in fact, if we gave them resveratrol and the combination of eating every other day, we got some very long-lived mice and the combination was great. So that's one of the things I do to myself is give is have resveratrol and try to be hungry once in a while. Yeah, that's what the Okinawans do. They call it harihachi-bu, which is 80% false. So you push yourself away from the table when you're 80% false. There's a lot to that, for sure.

Having a lot of food and glucose in your bloodstream, just not a good thing. So getting back to how to mimic this, mimic exercise and and diet you can do it in in yeast you can do it in mice by either taking resveratrol we showed that was one of the ways to activate sirtuin enzyme that protects the the body but we have something that's i think more interesting now which is the nad molecule you mentioned so nad let me tell you what that is. Anyone who's studied biology will have heard of NAD, but probably forgotten about it because it's so boring. Yeah, it's the molecule that nobody really wants to care about. What we discovered is that it isn't just a housekeeping molecule for biochemical reactions. Germans discovered 100 years ago, you needed it for life. Without it, we're dead in 30 seconds.

But what became interesting was in, thanks to Lenny's work when I was in his lab, and then later in my lab, we showed that the NAD levels of an organism are important for controlling the sirtuin protective enzymes. And as they get lower, they're not as active. And if you can get them higher, either artificially or by exercising or dieting, they get kicked into action. We get the benefits of calorie restriction and exercise without actually having to do those things. But they're added to it.

I don't think that's a good message. No. I was going to add to that, which is, but if you add them together. Is that it? Well, we just published last year, actually, in the journal Cell, that if you have a mouse and you give it an NAD boosting molecule and you exercise, then they become super mice and they can run beyond. Okay, that's good. So it's a lot of added value if you eat well and exercise.

Oh, definitely. Because I remember reading original studies way back when and I was like, wow, these mice were eating terrible diets and they were metabolically younger. They were fitter and they didn't do any exercise. I'm like, whoa. But then I was like, wait a minute, it's 1,500 bottles of red wine. It's not going to work. Yeah.

Well, in the resveratrol study, we did show that you could live, make a mouse live just as long on a high-fat diet as a healthy mouse with resveratrol in the diet. But I don't want to send the message that that's all you have to do and you'll be fine. No, definitely. There's other things that go go wrong and we're not mice after all. And you feel better if you're healthier anyway, right? So anyway, getting back to the NAD, we can raise NAD in everything from a yeast to a human by giving them what are called NAD boosters. And these are either NAD itself or

precursor molecules to allow the body to make NAD. The one that we use a lot in my lab is called NMN, nicotinamide mononucleotide is its real name. And the cells in the body take it up. There's a transporter. They get sucked up into cells and they immediately convert it into NAD. And we can see that there's a spike of NAD produced after NMN after about two to three hours. And then it eventually goes back down. But what we are seeing, especially in mice where we can take out tissues, look at tissues and blood, is that that has phenomenal effects on the body's protective mechanisms through, largely through the sirtuins and mitochondrial activity.

So on the market, there's a lot of these products out there that are being sold as NAD or some varieties of them, combining them with bisferatrol. Is it ready for prime time? Should people be running out and getting this stuff? Or is the data not there? I mean, is there clinical studies? There are a few clinical studies.

So Lenny Guarente and I, he's my mentor, we took two different paths. And I can only guess why. I think one was that Lenny's, I think, 15 years older than me and clinical trials take about a decade. So he was in more of a rush than I was. So he's gone the supplement route and decided to use that supplement to test in clinical trials. And he's just had a paper that came out I think yesterday in Parkinson's that looks really promising that Parkinson's patients do better on his combination of another

NAD booster called NR which you can buy and a resveratrol analog called terastilbene. Now that's actually one of the first studies if not the first that says that there's some positive benefits in people. There have been quite a called terrorist to win now that's actually one of the first studies if not the first that says that there's some positive benefits in people yeah there's been quite a few safety studies and so far everything looks safe uh but i know that mitochondria are the main organelles are the things that get injured in parkinson's and that mitochondria is exactly the cause of parkinson's in the sense when the mitochondria aren't working well, you can't have proper motor function

because it runs your muscles and they're easily damaged by toxins and other things. So using something that helps upregulate, and I've had patients where I've given them NAD and their Parkinson's tremors get better. It's impressive. Fantastic. Yeah, I hope that this is the first glimmer

that this is a really big change in how we can approach many diseases, not just Parkinson's. So Lenny took the supplement route. I'm taking the pharmaceutical route. They're both going to be complementary. There's no right way. We have clinical studies that are just finishing up phase one at Harvard where things look good. We can raise NAD in humans and no sign of toxic effects.

Our plan is to next year, early next year, go into diseases where mitochondrial are dysfunctional. Yeah. For example, in diabetes, half of primary relatives of type 2 diabetics, like son or daughter, brother, sister, they have a 50% function of their mitochondria, even if they're quote healthy. Yeah. So there's genetic things that regulate mitochondrial function that can be inherited but then can be modified through some of these approaches well they can in going back to the

mouse studies we we could we showed i think 2013 now that within a week we could make old dysfunctional mitochondria function and appear exactly like a young animal's mitochondria in their muscle. And to me, that was remarkable because we were told that mitochondrial dysfunction was largely due to mutations that were irreversible. And we can find mutations. There's no question about that. Very late in life in a mouse and in humans, they exist. But if you catch it early enough, and in the case of a mouse, it was about the age equivalent of a 60-year-old, we could turn a 60-year-old equivalent mouse back to a 20, 30-year-old within a week. And to me, that defied everything that we expected. Yeah, it's true.

You know, I first became interested in mitochondria because mine stopped working. Really? Yeah. I had, about 25 years ago, I lived in China and I got exposed to a lot of mercury and came back and got very sick from the mercury and it caused severe muscle damage. And my muscle enzyme CBK was like 600, which was really high. And I had muscle fasciculations and twitching and aching and pain. And I had severe chronic fatigue and my system just shut down. I went from like riding my bike a hundred miles a day to not be able to walk up the stairs. My cognitive function basically was

like, I felt like I was severely impaired. I had ADD and depression and dementia all at once. It was really bad. And so I began to sort of learn about functional medicine and mitochondria and started treating myself by actually upregulating all my mitochondrial pathways and all the cofactors and nutrients and removing the mercury. And I've used this approach and it made me get better. My numbers are great and I feel good. And I see this a lot of my patients who have sort of these weird sort of mitochondrial problems. So my wife has this. So if she goes for a walk or aerobic exercise, she'll feel crappy afterwards. And there's a syndrome of patients who just, when they exercise,

they don't get the runner's high, they don't feel good and they feel tired and wiped out, have to take a nap. And so I started to say, well, why don't we just try to give you a mitochondrial cocktail so I gave her a whole bunch of things including NAD, CoQ10, carnitine, ribose, some amino acids, B vitamins I don't know something else maybe and and should we do that before she'd go for a walk and no problem and I've seen this over and over again so I think you know it's it's a lot of these things that we have to think about not not just sort of one pathway, right? Yeah. Well, what's been amazing to me is that we used to think aging and these diseases were one-way streets. And we were lucky if medicine could help and slow down the disease.

But what you're saying and what I've learned is our bodies are remarkably good at healing. Yeah. Better than we thought, as long as you just tweak them the right way. And we're at that point in medicine and history where we have a fundamental understanding. It's not perfect. We have a lot more to do. Future generations will look at us and think of us as primitive. But we do have the tools right now to be able to change a lot of our disease processes and our aging process as well.

It doesn't surprise me that this is happening. With my father, he was going downhill. He was approaching 80. He was seeing his friends go downhill. He started taking the NMN and saw, in his view, the same thing we saw in the mice. What we saw was it wasn't just mitochondria going up. We actually found that the muscle started growing new capillaries

as though they were being exercised. And so his blood flow. You speak American and Australian? I try. I try. You've got a global audience, so may as well. Sometimes when I'm watching these English shows with my wife, she's from New Zealand. I literally have to pause the show and say, what did they say?

And she's like, we're watching The Crown. And, you know, I'm like, what did she say? She like translates and then I'm like, okay. Right. Or Game of Thrones, like, what did she say? She like translates and then I'm like, okay. Right. Or Game of Thrones, like, what did he say? Yeah. Well, stop me if I'm unintelligible. No, you're good.

You're good. You've been here a long time. So one of the things that is remarkable is, so one of the things I've found is that aging is also caused by a lack of blood flow. So you build up of toxins, lack of oxygen. And by inducing mitochondria to get them healthy and give them more energy, more of the ability to take in the nutrients and get rid of the toxins.

In mice, it's remarkable. In people, we think we'll be able to give them a lot more vitality. If my father's any indication of what we're going to see, it's going to be remarkable. We haven't tested it on vascular dementia, but i'm hopeful that this could be a way around that i've seen data somehow on alzheimer's and nad2 right an amyloid yeah there's some at least in mice do you know of any human results you know in mice yeah no pretty exciting so does nad also affect inflammation does it affect glucose and blood sugar?

And how does it work to those other mechanisms that are so central to aging? Yeah. So the sirtuins do a lot. They control blood sugar. They control liver and the pancreas, the muscle. So they do a lot. And often people say this sounds too good to be true, but it's not just my lab. It's now hundreds of people working on this.

On the blood sugar side of things, that was shown way back in 2012 by Shin MI at Washington University in St. Louis. So yeah, it does reduce blood sugar. It controls the pancreas insulin levels. It controls uptake of blood sugar. On inflammation, we know a little less about that, but my lab has done a fair bit. We haven't published a lot, but we find that as macrophages, one of the main inflammatory cells in the body, as they become hyper-inflammatory, they move into that stage. That requires NAD. And if you control that and prevent them from chewing up their NAD, which they need to, to convert into the inflammatory state, we suppress inflammation. So what we're finding is that if we give them our NAD booster,

or we block them from chewing up their NAD as they convert into this inflammatory state, we can reduce inflammation. And one of the problems with aging, we think, is that the NAD levels of these cells across the body, they go down with time. And not so much in the bloodstream, but in tissues, we think that the levels of NAD, such as the skin, we can measure that go down about half by the time you're 50. I don't know about a 60-year-old, but I'm sure you're looking after NAD. I'm hopefully, I'm taking it. Yeah. Well, that certainly is a way to boost it.

I like to sort of experiment on myself. So I try to put things the other way. Yeah, me too. If we wait 30 years for this all to be proven, we'll be gone by that point. I mean, my view is, what's the risk? What's the benefit? What's the cost? What do we know?

Like, is there a scientific premise that makes a reasonable explanation of why this should work? Is it safe, right? Does it cost a million dollars or 10 cents? And, you know, just some simple metrics that allows you to sort of try stuff with pretty much impunity. For sure. Well, let's get into that,

because that's a good point. The NAD levels are 50%. You get them back up to a young level or even beyond. That's when we see this reversal of aging. So that, I think, it makes sense what you're doing. Of course, we don't have proof yet, but we will. A lot of people reversal of aging. So that I think it makes sense what you're doing. Of course we don't have proof yet but we will. A lot of people are doing IV. Is that better? I don't know. We've done IP which is in the gut for mice. Yeah. I've heard a lot about it. I think it makes sense that that should work

just as well. But getting back to the risk-reward thing of that, that's really important. So it's a fact that a lot of these molecules are relatively cheap. In the case of metformin, what is it? Less than a dollar a day. It might be a few cents a day for some countries. Okay, so that's not a lot of money. All right? That's the cost. What's the risk? Something like metformin has been in probably 100 million people used for the last 40 years risk is extremely low no there's some side effects like gut issues and everything yeah exactly you're a real doctor i'm just a phd but metformin you can have you know i think the biggest risk is you'll

have an upset stomach but there can be some severe side effects you want to do these want to do these things under medical supervision do some blood tests okay So now we know the cost, we know the risk. Okay. So I'll just use metformin as an example. The downside, what's the upside? Well, the upside is you might have a few extra years, maybe another five years of healthy, longer life. That's a pretty good trade-off. I think what most people have trouble in the calculation that we just did, and you and I have done this calculation similarly, is what's the risk if I don't do anything? Yeah. All right. But most people are in denial. You know, when you're five years old,

you realize that everything dies. Your parents, you'll die. It's horrifying. Every kid goes through this. And we don't remember typically going through this. I remember. You know, it's horrifying. That may be why you and I do what we do, because we haven't forgotten the shock. But I think most of us, we don't like to think about this every day. It takes a lot of guts to think about your loved one's mortality, and it's even worse if you seriously contemplate your own mortality every day. That's brutal.

You don't want to do that. But if you do think about it at least once in a while, that calculation that we just did becomes pretty easy to do. Hey, everybody. It's Dr. Mark. Now, you probably figured out by now that I'm super passionate about getting regular deep restful sleep. It's a foundational piece for

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and kind of prompt, gently prompt my body to respond by becoming better at burning fat. And we call it fat adapted. And when you become fat adapted and your muscles start to get comfortable burning fat as the primary source of fuel while you're moving about your day, not just sitting around doing nothing, but while you're walking and then eventually while you're exercising. And you get to the point where you can derive 85, 90% of your energy requirements from fat if you become good at this. Your body fat or the fat you're eating? Exactly. Your body fat or the fat you're eating?

Exactly. Your body fat or the fat you're eating. Exactly. Yeah. So people talk about card loading. You only store about 2,500 calories. Yeah. But for fat, you probably got 30,000, 40,000 calories of fat on your body.

Absolutely. It's a lot bigger energy store. By the way, 30,000 calories of fat, that's just like 10 pounds. Right. I got that. Right. You know? So, I mean, and I could walk 300 miles without eating. Right. Not that I'm going to or want to, but I could. You are? Okay. I got that. So I mean, and I could walk 300 miles without eating. Not that I'm going to

or want to, but I could. You are? Okay. Theoretically. So the idea is to develop this metabolic flexibility. Both those things don't sound fun to me. No, no, no. Of course not. Walking 300 miles or not eating. This is all hypothetical. But when you become metabolically flexible, you're able to derive all this energy from your stored body fat. And then an amazing thing happens, which is the liver, when you withhold carbohydrate, which becomes glucose eventually through the digestive process, when you withhold carbohydrate. And just to be clear for people, when you say carbohydrate,

you mean refined starchy carbs. You don't mean broccoli, right? Okay, so we can make that distinction. I mean all carbohydrates, but I'm going to put a big asterisk by broccoli and say that when you go keto, you can eat as much vegetables as you want. That's right. Okay, so green leafy vegetables. And they're all carbohydrates. They're all carbohydrates, but they're locked in a fibrous matrix. So what we're talking about is

how accessible is the amount of sugar or the carbohydrate that you take in real time to the body. And if it's made less accessible because it's locked in a fibrous matrix, as in the case of broccoli, that's fine. Or any vegetable. Any vegetable. I mean, you know, for picking on my favorite vegetable. So you not only become good at burning fat, but then the body starts to, you create these ketones in the absence of glucose. And people would typically say, well, you know, I'm feeling woozy because my blood sugar is low. My brain isn't working because my blood sugar is low.

That's why they feel like they need to have a meal. That's why they feel like they need to have a snack. Because they get, you know, they have these wild blood sugar swings throughout the day because they've been so dependent on a regular supply of carbohydrate to keep their glucose up. Well, when you cease doing that for some length of time, the body gets wise. And the brain goes, well, look, I know how to burn ketones. I just haven't done it for a long time. So the brain becomes quite adept at deriving energy from ketones.

The whole theory that you need glucose to fuel your brain, that's a false? That's correct. You don't need it. Like one of the things that's become kind of a... Because you're supposed to use 25% of all the glucose, right? 25% of your energy. So... Right, that's different than what I learned in medical school.

Yeah, yeah. But you're saying that's wrong. No, so the brain, let me put it one way, which is that there is no dietary requirement for carbohydrate in human nutrition. Yes. So you should just unpack that because there are essential amino acids for protein. There are essential fatty acids from fat.

But there is no such thing as an essential carbohydrate, and we don't need them. Correct. Now, we don't need them, and I not suggesting that that we should never consume them but but the reality is we don't need them because we have this elaborate and elegant mechanism that takes stored body fat and in the absence of any food allows us to live for five six seven days not just survive but thrive and be mentally alert and to be willing and able to live for five, six, seven days, not just survive, but thrive and be mentally alert and to be willing and able to hunt for the source of food. Because remember, throughout most of human history, we didn't have three square meals a day. We had food and then we didn't have food.

And so the design of the system, and again, this elegant system, phase one of the system says, the brain, when it comes across food, you got to overeat because you don't know where the next source of food is going to be. And so when you overeat, you take the excess amount of energy that is in the food and you store it as fuel that you get to carry around on your body. By the way, conveniently located right over the center of gravity, the belly, the butt, the hips, the thighs. It's such an elegant system that we would be able to carry this fuel with us for long periods of time and not worry about, oh my God, it's noon and I'm going to get hangry because there's no food around or there's no deli nearby.

You have the ability to use that fat for energy. You just, you'd use that fat for energy. And that's how the system's designed. So unfortunately, we get to today where we've lost the ability to so we're very good at storing fat and we still are wired to overeat but because i mean yeah there's like 200 genes that protect us from starvation yeah but none that help us deal with abundance and excess so it's an artifact of civilization so we kind of have to override that with our cognition.

But one way to do that, again, is to use a ketogenic way of eating for some period of time. Again, not necessarily for the rest of your life. What is keto? Define keto. So keto to me is cutting carbs back to 50 grams a day or less. Which is what is 50 grams in terms of a food? Like a bagel? Yeah, pretty much.

Like a bagel with some jam on it and you're already over the top. Or any, like if you got rid of bread, pasta, cereal, rice, cookies, candies, cakes, sweetened beverages, sweetened drinks, and all you had was, oh my gosh, real food. Broccoli, Brussels sprouts, cauliflower, salads. You would be fine. You would be within that 50. You'd be hard-pressed. Could you have grains and beans?

No. So you don't have grains and beans on a keto, on a true keto diet. Now, we'll talk about what pedo looks like. Pedo, okay. Or paleo keto, or what are we going to call it? Your pegan version of keto. What's it going to be?

Keegan. Keegan, okay. It's a Keegan diet. It's like a keto vegan? Yeah, yeah. I have a friend who's a keto vegan. Yeah, yeah. So you can do it for sure. It takes some adherence to this.

At the end of a couple of weeks though, you have shifted your metabolism to one of greater efficiency. So it takes like three weeks to adapt to it. You need to make sure you have enough fluids and sodium and magnesium because otherwise you feel the keto flu. And some people still get the keto flu, but it's not like the flu. You feel achy and tired. That's your brain going, where's my glucose, dude? And until the brain kicks in and says, wow, these ketones are amazing.

The liver can make up to 750 calories a day worth of ketones. Wow. Like, chew on that for a second. That's unbelievable, right? So when you look at how we're designed for survival, if you look at— I mean, not from diet, but just from your fat stores. Correct. Yeah. Yeah.

So, and, you know, we have this stored body fat, and when we cut off, just theoretically, if, like, say you do a fast, which we can talk about what that looks like, but you do a five-day fast, you become a closed loop. It's amazing that you— that the body takes fat out of storage, combusts some of it in the muscles to get you through your day. And people who do five-day fast, they work out, they'll exercise, not hard, heavy. So you combust some of that fat in the muscles. Some of that fat, as you take those triglycerides and you strip out the glycerol, becomes a backbone to make enough glucose through gluconeogenesis

to supply whatever amount of brain cells do require some glucose. It's not a big number. It might be 40, 50 grams a day. The liver makes ketones. The brain thrives on ketones. The brain prefers ketones. Yeah, the brain does way better on fat than on sugar. Well, on ketones, yeah, because the brain doesn't burn fat, but it burns ketones.

Ketones are derived from fat. Are derived from fat. So you have this substrate, this fatty, this fat substance that then can become combusted by itself as fat. Part of it can be used to actually make glucose if needed. That's why you don't have an external need for carbohydrate and glucose. And then you can make up to 750 calories a day worth of ketones. Now, one of the best things that happens in this scenario is that, again, epigenetics at work turns on genes that cause the body to spare amino acids and spare protein. So whereas normally on a day-to-day basis, you might eat a big meal

and you might have more protein than you need. And then your body has to kind of go through this work to deaminate it and pee it out because it's too much. You don't need that much. And so when you become this closed loop, this closed system, the only reason you need the amino acids are for structural, for repair, for building and repairing things. Not to make sugar. You don't want to combust. Some people have a false idea about keto, that it's all like steak and bacon and cream and all this stuff.

It's not necessarily that. No. In fact, you can eat too much in the way of, well, I mean, a lot of people who first come to keto do so because they, I heard that I can eat 4,500 calories a day and not gain weight, you know, and I'm like, well, yeah, some of the science shows that, but that's horrible because that's a bad idea. Because first of all, if you want to burn off your stored body fat, eating 4,500 calories a day will never tap into your stored body fat. That's just, you you know that's just trying to prime the pump with this external source of fuel that that's fat that's circulating through

your through your bloodstream and and and that amount of calories because you're not generating insulin which is a which is a nutrient storage hormone um the the nutrients have nowhere to go the body has to figure out how do i burn this stuff off? I can't store it as fat. So the body undergoes this thermogenic, high heat kind of thing. Well, that's so powerful because people don't understand that if you don't have insulin, which is only produced by eating carbohydrates or protein, can also include insulin. If you don't have insulin, you can't gain weight. So if you're a type 1 diabetic, the classic symptoms are polyphagia,

meaning you eat everything in sight, and you lose weight. So they could eat 10,000 calories a day and lose weight because they have no insulin, which is required to store the fat on your body. So the best way to get your insulin down is to cut out the starchy carbs and to eat more fat. Reasonable amounts of protein. And more fat and reasonable amounts of protein.

Yeah. So you don't make it up with, you know, you don't make the calories up with extra amounts of protein. Yeah, so 20%? Okay. I mean, I prefer to deal with hard numbers, like what's a good number for protein? Maybe it's 75 grams a day for a man as a minimum number, and maybe it doesn't exceed 120.

And within a range there, you're going to be fine. And then because the body is so efficient, again, at conserving amino acids, protein, that it doesn't even matter meal to meal or day to day. It might be on a four-day cycle. If you get 300 grams of protein in a four-day cycle, you're good because it'll just figure out with the different various protein sinks that we have in the body how to keep it and not pee it out. So back to this closed loop that I'm talking about. So you're combusting fat in the muscles.

You're making a little bit of glucose through gluconeogenesis. You're making ketones. Now we figure out that you don't really need that many calories to get through a day. Like we assume if we do that math that's online, you plug in your number and your height and your weight or whatever and your activity level from one to five and you come up with some number, oh, it says I can have 2,700 calories a day or 3,200 calories a day for maintenance. No bearing whatsoever on reality. We probably, if you, again, if you do the math, if we, for long periods of time, if we say that protein, protein shouldn't even have a calorie assigned to it.

It's like, it's structural. You don't burn protein, so why would you even assign a value of four calories per gram to protein? Right, but it can turn into sugar. It can. If you eat excess amounts. It can. So, you know, and I guess if you burn it in a bomb, you get some amount of thermic effect. So how do you know if you're doing a ketogenic diet properly?

Well, the main thing is can you go a meal or two, skip a meal or two, and just feel just fine? And if you can... It cuts hunger. So ketones, it cuts your hunger. The number one benefit from all of this is getting control of hunger, appetite, and cravings. That's what everyone reports when they finally hit that keto zone.

So it's not bad willpower that people want to crave and eat other food? It's just biology, right? It's biology. It's absolutely biology. And people come to this point pretty quickly where they go, Jesus, Mark, three meals a day is just too damn much food. I just don't feel hungry. I feel like I'm overeating at three meals a day. And so typically what they do is skip breakfast. They wake up in the morning. I have a cup of coffee. I go about my day. I do a hard workout. I'm like, not only do I not need to eat, I don't

feel compelled to eat. I don't want to eat. And I might have my first meal at one o'clock or one o'clock. It's like time-restricted eating. It's what it is. Yeah. And so then you get to the point where you're eating maybe two meals a day. And then from there, it's like even those two meals feel like if I have two regular, what would have been in the old days, regular meals, now it's like I'm going to have lunch, kind of a smaller lunch because I want to enjoy a regular dinner.

If I have a regular lunch, then I won't be hungry for dinner. It's amazing how hunger dissipates in this context. But you don't get super skinny. I mean, you look good, right? I'm at work to keep my weight on. Although I noticed, Mark, is I actually have a problem. If I don't have things like sweet potatoes or some black rice, something like that, I will lose too much weight.

Do you lift weights? I do. I started. Okay. Lifting weights is what causes you to keep muscle on. If you don't lift weights, especially as you get older, like when you get to be 45, you'll see what I'm talking about. I'm 60.

I passed that mark long ago. I'm just messing with you. But I'm biologically 39 because I did my telomeres. As you get older, the importance of lean tissue becomes more and more critical muscle is the forgotten organ it's you forgot and people think well if i'm if you know if i'm jogging in my 50s and 60s and 70s or you know riding a bike that that's accomplishing what i need to accomplish and it's not it's actually it's much more important to spend some time in the gym lifting heavy weights like the heaviest weight you can lift without getting hurt.

Yeah. Without getting hurt is a key component. I don't want to. So my trainer tells me I should do like more reps, like I do three sets. Yeah. And I do, you know, it's pretty hard, but it's not like my maximum that I can do. Sometimes it is, but is that the same or is it more better to do heavy weights? How many reps do you do?

Are we talking six or 35? I do like 10 to 12 and then I do three times. That's fine. That's a standard. That hasn't changed in decades. That's still, and there's no right answer there. There's no magic. It's like whatever you feel good doing.

Is that building enough muscle or should I do more heavier weights and fewer reps? Heavier weights and fewer reps builds more strength over time. But there's no, I can't tell you that that's where you need to go. But I'll give you an example. It's sometimes the type of weights you're doing. So if you're just doing bicep curls, you know, that's, you know, for the beach,

but that doesn't really impact bone density, you know, muscle mass throughout. So hex bar deadlifts. You ever do those? Yeah. Yeah. That's the best thing you can do. What about just a regular deadlift? Yeah, they're good, but I'm too concerned with my back.

So I lift heavy with a hex bar deadlift. Oh, really? Yeah. But I do it once every week, and I do three sets of that. I keep adding weights. How much do you do? I do up to 300 pounds. I do one to two rep max on 300.

Oh, one to two reps. Yeah, I can do 335 on one, but it's too much. I wind up taking too long to do it, and I'm afraid... Again, I don't want to hurt myself. So I do... But that's like... That one exercise impacts the entire body. Yeah.

You know, it's not just what you would see obviously from doing the weight of the glutes and the lower back and the hamstrings and the quads, but it's pulling on the shoulder muscles. My grip strength is sometimes the thing that gives out more than anything else. But that one exercise then has an effect on the pulse of growth hormone and testosterone. It involves so many muscles, including major muscles, that then when you go do the pull-ups and the push-ups and the dips and the squats and all the other lunges, then you get the impact is greater. The muscle-building effect is greater because you did that. Yeah like that I like that so I should do that first or last or

whatever but I mean if you do it first a lot of times you'll like you know you won't have the strength to complete the other stuff so what is the biology of doing you mentioned you can burn fat but why is that better like what does it do in terms of longevity what What does the science show? Well, burning sugar is, in and of itself, it produces reactive oxygen species at a greater rate than putting, combusting fat through the mitochondria. So the more energy you can drive through this metabolic pathway that uses the mitochondria, the better off you are. A lot of times people burn sugar in the cytosol of the cell, not even... The way I think about it is interesting. So when you eat a lot of sugar

calories and starchy calories, it burns dirty in your mitochondria and releases a lot of waste products, which is these reactive... Oxygen species, yeah. Or oxidative stress or free radicals that are driving aging. And when you burn ketones, it's more like hybrid. Yeah. Like an electric, like an electric bill, it burns clean, right? Like a 93 octane. Yeah, it burns much cleaner.

Yeah. Is that true? It's true. I mean, that's the simplest way of looking at it. Then there are other nuances to this, which are when you become good at burning fat, then when you skip a meal or when you have this very easy to manage compressed eating window, all the good stuff happens when you're not eating. So the longer you can go, and that's why fasting has become the rage, the longer you can go

without eating, the more your body says, oh, this is a great time to do some house cleaning. And the term autophagy is thrown out probably too much now. But the body does tend to want to clean up and consume damaged proteins. Autophagy means like you're literally eating yourself. Correct. So eating all the waste products. Eating the waste products. Pac-Man goes around and cleans up the place. Correct, and if you never fast, you just become this increased collection of garbage in your body. The whole three meals, three snacks, eat late at night, after dinner snack, and wake up eating right away, that's a bad idea.

It's a bad idea. And what's ironic to me is that even going back 15 years ago in the bodybuilding, in the weightlifting, in the general health community, the mantra was, don't go more than two hours without eating. You bring your Tupperware, you know, little meals with you with, you know, some amount of protein, some amount of carbs, no fat, skinless chicken breast, and, you know, all that stuff. It was a horrible concept. And yet, the thought process was, you know, you don't want to cannibalize your muscle tissue. And if you go more than three hours without eating, you'll cannibalize your muscle tissue.

Now, all of that was predicated on an assumption that glucose was the primary fuel that we needed. When we ran out of glucose, it would cause the brain to go into a state of, oh, my God, send a signal to the adrenals to secrete cortisol so we can basically melt some muscle tissue and send some amino acids to the liver to become glucose. Exactly. It was a horrible, again, it was all based on a concept that somehow assumed that glucose was the muscle fuel that we needed. And if we didn't manage glucose, all hell broke loose. Now we know that fat is the preferred fuel for human movement and human activity, and that ketones are not just a legitimate alternative energy source. They're probably a preferred energy source in many cases. Now, as a doctor, I see a lot of patients, and I

test them, and I see the results. And it's humbling because you can come up with all these great theories, but then you see the individual in front of you. And I've had patients I put on a ketogenic diet eating butter and coconut oil all day and they lose 20, 30 pounds. Their cholesterol comes down 100 points. Their triglycerides drop. Their good cholesterol goes up. Somebody else does that and all their numbers go terrible and they start getting really bad

cholesterol numbers and and i i'm one of those guys if i eat too much of saturated fat i get in trouble and i think how how do you understand sort of how to personalize this so all right so a couple things first of all um you know we've never had conversation, so I don't know what your stance is currently on this. But, you know, I've been pushing for 15 years to take the weight off cholesterol as a bad guy. You know, the cholesterol is not the proxy. In the blood or in the diet? Both. But let's just talk blood cholesterol right now.

I don't think cholesterol is a bad guy. Cholesterol is one of the most important molecules in the human body. It's integral to life. The body makes 1,300 milligrams a day, whether or not you have any in your diet. And to vilify it and spend a trillion dollars for the last 15 years to try and eradicate it in humans is absolutely unconscionable. Through statin medications. Through statin medications. And I shared with you before the show. So I just had some blood work done. I'm between 245 and 290 on my total cholesterol. But my HDL is 98. That's the good cholesterol. That's the good cholesterol. And my triglycerides are always below 75, sometimes 45 or 50. My A1C is 4.9, which you know to be-

That's your average blood sugar, which is really low. Really low. Fasting insulin is between 6 and 7. It can be as high as 45 in some people. So all my markers are great, except that if you didn't ascribe to that whole cholesterol theory, you'd go, oh my God, Mark, we got to put you on... Everything looks great. By the way, I had a full scan of my carotids and all my blood supply to my to my art to my you know my coronary arteries my liver i mean they were digging in so deep i thought oh my god they're they're looking to see if i have colon cancer but they were trying to get to get at my kidney my kidney supply and they said you know you're clean you got like the blood supply of a 30 year old it's clean as can be that's all that

counts mark i don't care what my cholesterol numbers are. But aren't some people more at risk, though? Some are. But again... Is lean mass hyper-responder phenomena? Yes. And it all, I think, comes down to... And I'm not a doctor, so I'm only giving you my opinion.

You can opine with greater... I guess you have more liability for saying it than I do. I have no liability as long as I say I'm not a doctor. But it's inflammation and oxidation that are the primary culprits here. And so if you have an otherwise inflammatory lifestyle, inflammatory diet, we can talk about sugar, we can talk about stress, we can talk about, you know, and then we can talk about some familial predisposition. Yes. But in general, so back to your two people, some succeed wildly on the ketogenic diet and some not so much. But the not so much, if you're evaluating just on short-term blood markers, I'm not going to say it's not working. I'm just going to say that's, you know, if you're keto and you're good at burning fat, you got to transport the fat

somehow to the muscle cells. You've got, you know, there are a lot of things going on here. Yeah, we just don't know. And we just don't know. Now, some people having said all of that, some women in particular, are not good responders to keto. It may be... Who shouldn't be on it? Well, so I think pregnant women probably, you know, you just work with... If you want to do this and you insist on doing this, work with somebody who knows what they're doing, right? And I wouldn't, you know, I wouldn't introduce a three-year-old kid to a ketogenic diet, you know?

You think it's something everybody should be on? I think at some point their lives, everybody should be on it because it's the human experience. So you think cyclical keto, that's the idea. Cyclical keto, yeah. So do you ever go above the 50 grams of carbs? Oh my God, I have... Last night, I'm visiting here in Los Angeles. My daughter is a great chef and she made a lasagna last night. Like, I'm not going gonna not eat two servings

of that i mean you know and it was somebody's birthday and we had some pie and you know i didn't i didn't sleep as well as i as i would have had i not done that but i also like i'm totally comfortable in in the fact that you're in and out in and out and that's that's what we historically did that's exactly so when we talk about you know know, were humans, you know, always keto? No, there were periods of time when we were, there was no access to food. You were like automatically, you were obligatory keto when you didn't eat. Yeah. But because you didn't eat processed crap and industrial seed oils that would infect your insulin sensitivity and all these other things, even if you came across a treasure trove of bee honey or it was late in the season and you had a bunch of fruit,

you'd store it as fat, but then you'd go right back to being keto when the food supply was cut off. Exercise is a big thing, and it's not necessarily extreme exercise, but deep breathing, for example, walking, lifting light weights, are all good exercise that will contract the muscles and pulse forward the lymphatics. So in the exercise realm, I think it's very important with your deep breathing and with your movement of the muscles will increase lymphatic flow. The other thing is plenty of good pure water because you need, you know,

there's a cell gel system there. The lymph can turn kind of sticky, like, like a cell, a gel and you want to keep it pure and flowing. So plenty of good, clean water. As far as foods, the plants and the fruits, I'm not saying that you have to be a vegetarian, but you should have the majority, thinking about plant-based diet.

I call it plant-rich. Yeah, plant-rich we know a diet like you know i call it plant rich yeah plant rich we want to call it and green leafy vegetables ginger turmeric spices things like that will will always make we have a recipe guide i had we had uh made there that is all lymphatic stimulating. So you keep the polyphenols. For example, in olive oil, polyphenols of olive oil are very important. And that's one of the things that we look for in pure virgin olive oil is the polyphenols. So you have green leafy vegetables, you have herbs and spices, you have onions, garlic, things like that will all increase lymphatic flow. And then certainly the idea of stress modification to suppress the epinephrine and things and this ACTH and stuff like that which constricts the flow so these things in spirituality doing yoga and meditation and things like that get get the

lymphatic flow going it yoga is called like an internal massage yeah the the plans of the yoga are to increase the the um the massage of the internal organs so those are the things you can do and there's a whole you know we have a chapter on on meditation and yoga we have a chapter on exercise and a whole bunch of recipes that you can use. And we tasted some of them, and they're pretty good, aren't they, Mehmet? They're fabulous. Yeah. I think those epigenetic, those are things you can do to change your gene,

you know, change what the genes produce. And it's important to do things we have control of. And once we understand why we're doing it i think we will apply it more fervently and we'll have better control of our health yeah you mentioned yoga and i think yoga is one of those things that's sort of underappreciated for its effect on lymph flow and i i created a detox program years ago and and i work with a yoga teacher to create a lymph yoga program to actually help move lymph through the body there's twisting there's bending and all the massaging you do it's

really one of the most powerful tools i think aside from just you know walking and regular exercise but it really can be a powerful factor uh and you and you mentioned the spices and the polyphenols you know we we don't use them much in this country. It's just amazing to me. Most of our food is so awful and bland. It's flavored with salt, sugar, fat, additives, and chemicals. I just got back from Turkey, where you're from, Mehmet, and I went to the Spice Bazaar in Istanbul. It was just like a, you know, like an incredible kaleidoscopic bonanza of colors and spices. And I brought some of them back with me that are just used every day as part of their cuisine.

And we don't do that here. But those cultures really have understood the role of these things in our diet as health-promoting factors. And the olive oil you mentioned, I was where your dad, I guess, had an olive oil orchard. And I was being schooled on the ways in which you have to actually maximize the polyphenol content.

Because most people, when they pick olives, they shake the tree. And then it, like, falls to the ground and they pick them up and then they smoosh them and they get olive oil. They have them hand-picked. Every olive is hand-picked so it doesn't hit the ground and start to become acidic and lose its polyphenol content. So, I mean, we have such an amazing world we live in with all these tools, with all these foods, with all these spices, with all these potential therapies that we don't take advantage of that help enhance our health. And I think that if people just pay a little attention to what does mess up their limb system and what enhances their limb function, their health and their life will be a lot better, right? Yep.

Yeah. Yep. So do you have a daily, like, limb practice? Or how do you think about incorporating it into your life? I mean, there are so many things you have to do, right? Eat right, meditate, exercise. But how do you start to make simple changes that could help people say okay i'm going to do this because this is well yeah i i what at my my age i'm unlimited to walking on uh walking of

three miles an hour for a mile or two in the mornings and then i lift five-pound weights just to get them so I can play golf with this guy. Otherwise, he tries to embarrass me. What do you mean? He's not competitive. Hold on a second. Let me just be clear here. Dad is 84 years old, and for any golfers out there, he shot his age two weeks ago. Oh, wow.

And then that was the warm-up. The next weekend, we played, Dad and I, against my two brothers-in-law, and we beat them, which is unheard of. Wow. And Dad, as he hit the winning putt, winked at them with great joy in his eyes. So I knew that was the win.

I might achieve hitting my age when I'm maybe 140. Exactly. Like most of us. I'm not very good at golf. Well, that's what it is. Mark, can I ask? The thing is that these common ailments that you're talking about that Dad was listening through, I mean, they exist because we don't have good solutions for them, right? So we had a great solution for libido, and there are some pharmaceuticals, obviously, that we can start using now, especially for women.

But the Chinese say, you know, gojiji berries nuts siberian ginseng you know they have their game plan like lice lychee berries which later lychee that fruit is sort of reminds you of something it looks like testicles but things like sleep the chinese use congee they use a lot of congee which is uh a grain but they also use massage and the main tip for massage is it stimulates lymphatic flow, which dad showed and others have proven. You massage your feet, you stimulate thoracic duct lymph flow. So that's very hard to even connect those two structures. How does your feet affect lymphatic flow in your chest?

On the other hand, the Chinese do acupressure and acupuncture in the feet, and they can stimulate parts of the brain that coincide with that spot. So there are clearly connections between parts of our body that we don't understand with the traditional Western model that you and I, all three of us, participated in. It doesn't mean they're not right. We haven't discovered them yet. We will one day. But why wait? No, it's so true.

It's so true. It's so true. I think the ways in which these ancient systems have developed models for maintaining health and optimizing health and creating health is so foreign to how the three of us were trained in medical school, which was find the disease, kill the disease, and then move on. Just that was it. And it's exciting that you both sort of are coming at this in a different way that help us sort of understand a new way of dealing with some of the challenging conditions that we suffer from. And I think, you know, fatigue is another one that people have. And I think fatigue is probably really connected to lymph flow because fatigue is connected to the toxic burden and to inflammation and oxidative stress. And if your lymph system is not working, it's hard to function with that.

And a hot bath, a hot bath will also stimulate lymphatic flow most likely. It also happens to be the foundation of traditional Chinese medicine treatment of depression and fatigue. So if you Google, right, if everyone listening now to buy a computer, Google, why am I? It will auto complete, so tired.

It will do it. I mean, it's amazing the first right but why am i sounds like a philosophical spiritual quest you know why am i will auto complete on google so tired of so exhausted you know because that's the number one thing we search you have uh come upon the lymph system as one of those critically foundational systems that has to function in order for us to be healthy. And when it's not, we age quickly. So, Dr. Lamont, tell us about how you came to understand that this is true, that it's not just about our cardiovascular system or neurologic system or musculoskeletal system, that there's

this whole other system in there that's pretty much ignored. And we don't really a lot of treatments for, but that actually responds to a lot of things that you talk about in your book that are available to everybody. So tell us, you know, how did we sort of miss this and why were you interested in lymph system and how it impacts every aspect of our health? I mean, you've called it the secret river of health. What do you mean? Well, you know, when we were doing the heart transplants back, way back when then, I was involved in the first five, and they became very personal friends because we stayed with them for months. We didn't know what the heck was going to, what to expect, what was going on. So within a

short period of time, we had given these people good, healthy hearts with wonderful blood vessels. And within a short period, a year or two, year and a half, they developed, all died from galloping atherosclerosis. Their vessels had turned to 90-year-old vessels. And it was not only a professional failure, but a personal loss. And so it always stayed in the back of my mind. And when I left Houston, I was chief at Temple University School of Medicine, and we had a professor of pathology there, Betty Lausch, who was interested in foam cells.

So we got together and did a project on rhesus monkeys. We ligated their lymphatics from their heart, and sure enough, they developed early atherosclerosis. So I always kept this in the back of my mind, and I'd observe when we did coronary bypasses, we'd have sclerotic little white vessels following along the veins. And so I'd biopsy them, and they were sclerotic little white vessels following along the veins. And so I'd biopsy them and they were sclerotic lymph vessels and they were not there in the aortic valve or the mitral valve with no coronary disease. So, but it's so hard to measure the lymphatics. You can't measure a level of something or it's a low pressure system. You can't, it's very difficult.

So consequently for many years, you know, nobody really did a whole lot. And up until the last 10 years or so, there was nothing really said about the lymphatics. But we, in 1981, I wrote a paper. I figured the best paper I knew was the sciathoracic surgeons. I should have been in some other journal, but because the surgeons weren't too interested. But we showed that there was reverse cholesterol transport, the relationship with the lymphatics was important, and that's how the actual cholesterol got out of the arterial wall into the venous system to the liver by way of the lymphatics, and that was 40 years ago.

So your blood circulation and your lymph circulation are connected and they're interacting and moving things around like cholesterol all the time. And if one's not working, the whole system kind of breaks down. The whole beauty of the lymphatic system is that it is responsible for re-regulating our fluids because we lose about 10 or 15 percent of our fluid for outside our vascular system into our interstitial or this this tissue between the cells so we have to get that back in the lymphatics are responsible for getting it back in the lymphatics are responsible for getting every fat molecule back into the system. They're responsible for getting large proteins. Things like, you know, when you have a leaky gut and you have, say, casein or gliadin, the only way it can get away

from the sampling mucosa is to go through the lymphatics and get tested by a dendritic cell to see if it's good, bad, or ugly, you know. And that's what it's all about. And if we don't have the lymphatic system, it just doesn't happen. Well, so essentially what you're saying is when you have all these molecules that run around your blood and then they go out in your tissues and your body has to clean it up and then it has to check that if it's okay or not and it gets back into your lymph system and your blood system then you can kind of regulate it so the it's very difficult to to measure the the the anything because it's a very low pressure system so we can't measure like the arterial wall pressure or the lymphatic pressure the flow depends completely on the motion of exercise, what

your muscles are doing, squeezing them, the arterial pulsation, and its own innate pulsations. It has its own pulsation. It has smooth muscle in it. It has sympathetic and parasympathetic nerves. So it sends signals all throughout the body to have a general inflammatory response. And then the important thing, it has to shut off that inflammatory response. And if it doesn't shut it off, you get autoimmune or chronic inflammation. And that's what we're facing in a pandemic now.

Yeah, I want to get more into its functions. But for those of you who don't know what it is, I'd love, Jerry, for you to explain, you know, what is actually the lymph system? Where is it? How do we find it? What does it look like? What does it do? Give us sort of a background, because I think most people understand it. It's, you know, you have a liver and a kidney and a brain, but like, where's the lymph system? That's exactly, that was the problem in the, in fact, that it really deserves, it's a system that deserves, but it's always used as an appendage to something. It's, it says, oh, the lymphatics are with cancer. They think a lot of

people that it gets attracts attention because of the cancer, but it's, it's a system of its own that usually lies between the artery and the vein, the lymph channel does. But when we were in medical school, we didn't talk about the lymphatic, we talked about nerve artery vein. That was the neurovascular bundle. But the lymphatics are in there and they have to, if they go into spasm, they are not clearing the toxins. They're not sending the messages of the immune system. They're not getting the signals of protein and fat that will send messages out to the body. And then the messages aren't going back that shut off, you know, that shut off the inflammatory response. The beginning of the response you want,

acute inflammation is a good thing. It kills everything inside. It also attacks the normal tissue as it's getting rid of the toxins. But at some point, we have to send in cells and proteins to come in and stop that inflammation. And if it's delayed, there's more damage in the area. So everything that causes it to delay is caused by the lymphatic system not either being stagnant, not getting good water supply, not being pulsatile, being dilated or being constricted. For example, if you smoke cigarettes, you will get sclerosis of the lymphatic systems.

And, you know, cortisol release does it and adrenal release does it. So over the long haul, that's why stress creates problems. And what's interesting to me is we always say when we do these studies, Over the long haul, that's why stress creates problems. And what's interesting to me is we always say when we do these studies, you say, oh, look, people do better if they exercise. They do better if they have stress management. They do better if they eat a lot of vegetables and fruits. Point of fact is all those three things increase lymphatic flow. The exercise goes through the thoracic duct, and you breathe, the diaphragm sweeps it up.

It's got one-way valves, and it makes the fluid go into the venous system and to the liver. Polyphenols and flavonoids are strong lymphogobes. I mean, they suppress inflammatory markers. They do wonderful things, and that's why we know that, you know, vegetarian-type plant-based diet is helpful. And the same way with stress modification. If you're relaxing your body, you're not secreting the hormones that will cause sclerosis of

the lymphatic vessels so it's interesting to me that all these all the three things that increase lymphatic flow are things that will help every chronic degenerative disease yeah and so but it gives you an understanding and if you get that understanding you'll be more apt to do what you're supposed to do because it's not a mystery then, why does this happen? Because you can explain what happens with lymphatic flow when you do these things. I think first and foremost, we have to recognize that sleep, you know, you and I trained in an era where sleep deprivation or how little sleep you could get by on was a badge of honor. Yeah. So we need to shift that internal dialogue that we all have that, oh, if I'm sleeping,

I'm wasting my time and I'm not getting my stuff done. So first, honor the importance of sleep for your overall health and well-being and even your ability to stick to your intentions around choosing healthy foods and sticking to your exercise plan. Then create a sanctuary that's really conducive for rest and relaxation. Dark, quiet, cool, ideally electronics out of the bedroom, or turned off if you can. Getting rid of all of the light exposures,

even your chargers, you know, that have that little light. Yeah, like those lights, like those red, green lights on different devices. I'm like, that drives me crazy. I used to, I had a patient who told me she traveled around with black electrical tape whenever she went to a hotel and she would put it over all the little light sources in the hotel room. I travel with eye shades because you never know where you're going to be. So those two, quiet, calming. And I think this idea that you go, go, go, go, go, go,

hop in bed and turn it off like a switch, that doesn't work either. So building in a transition to rest and relaxation. If you can do an hour, that's great. And getting off the devices, not watching TV, maybe reading a book or journaling or doing something, taking a bath, stretching in the tub. I mean, there's all kinds of wonderful ways to ease into rest and relaxation. I like the hot Epsom salt bath and lavender drops because the lavender lowers your cortisol, the magnesium relaxes you and the sulfur and the Epsom salt helps you detox. That's my favorite as well. And then you go to your cool bedroom and you do your legs up the wall yoga, restorative yoga position and bingo, you've got your transition to rest and relaxation. So powerful. And alcohol obviously is a good practice for people. Yeah, that's a tough one. That's a tough one. So the rough analogy is this.

It's funny, when they asked partners of people with insomnia, how many of them were suggesting that they have a drink to go to sleep? It was about a third of them. So people think alcohol is going to help you sleep. And it might make you fall asleep. But then as it clears out of your system, there's an arousal that can exacerbate hypoglycemia. It makes you wake up. It's going to make sleep apnea worse. If you're a woman in midlife, oh boy, it's a bladder irritant. It's a hot flash trigger. So it's really affecting sleep in a lot of ways. The rough equivalent is there's about an hour of sedation followed by an hour of arousal. Yeah. So if you had a glass of wine at six and you go to bed at 10, it's probably not going to impact your sleep as much as if you have two glasses at eight or like your late dinner last

night, if you had a glass or two of wine. I had a beer. Yeah. That has another impact on your sleep. I just noticed it. Actually, I had an aura ring for a while and I was tracking my sleep. And I noticed whenever I drank, my sleep pattern was so disrupted. Quality of sleep, the depth of sleep, the amount of REM sleep, deep sleep, snoring, you know, all that. It's really interesting. And then caffeine also is another big one, right? Yeah, absolutely.

And we're all different in terms of our caffeine metabolism ability. Some people are really fast metabolizers. I happen to be one of those. But if you're a slow metabolizer, half of your cup of coffee from noon could still be in your system at nine o'clock at night. And most of the time, we're not thinking back to that new cup of coffee. With food, it's really about quality, quantity, and timing of food. It's all three. Yet another area that's impacted with the health of the gut microbiome is sleep. And data is suggesting that people who eat a wide variety of colorful fruits and vegetables

tend to have better sleep quality, whereas a highly processed standard American diet is associated with more sleep disruptions and less deep sleep. So quality matters. We already touched a little bit on the timing of eating. So eating your calories earlier in the day also helps re-regulate those circadian rhythms. So the clocks in the brain and the clocks in the body that are ideally going to be working in sync with each other, they're influenced by light, by movement, and by food. So when we line all those things up during the day, it's going to help us get the rest that we need at night.

So important. This is such good information. Let's talk about what are the challenges that you see in your clinical practice around women and sleep? And what are the main reasons that you're finding? And some of them aren't expected. And then let's go into how, you know, there would be traditionally approached by conventional medicine. And then we'll dive into functional medicine.

Sure. So I think the first thing is that some common sleep conditions like insomnia and restless legs, they disproportionately affect women. And they can have a connection to lifestyle. Sleep apnea, interestingly enough, gets underdiagnosed for women. And there's a lot of reasons which you can dive into it, but some of it has to do with stereotypes on the part of clinicians of thinking about sleep apnea being a man's condition, especially if they're overweight. A big, heavy old guy, right?

Right, especially putting weight on him. 300 pounds, right, yeah. But lean women can get sleep apnea too, and it may show up very differently. There's also the idea that when we look at times of hormonal fluctuation for women, whether that's before their periods or during pregnancy or the postpartum or the menopause transition, that can also cause an uptick in disrupted sleep. So hormone balance and regulating hormones can play a huge role in improving sleep quality. And finally, you know, disproportionately in the past, caregiving demands have fallen

on the shoulders of women. And I think that really became manifest or evident during the COVID-19 pandemic when you saw a bigger proportion of women than men experiencing an uptick in insomnia, anxiety, and depression. So they're all interconnected. Yeah. So women take on the burden of the families. They often, especially during the perimenopausal years, become the sandwich generation between raising their kids and taking care of their elder parents. And you're kind of in the middle of that, a little bit toward the tail end of it, but you kind of went through that. And it puts a lot of stress on women.

Also, I think there's some unusual causes of sleep that get missed by traditional medicine. And so like if you were a woman and you went to the doctor, like I'm having insomnia, what are they going to tell you? They'll probably tell you to take a sleeping pill. A little Ambien. A little Ambien, yes. A little Valium, right? And or maybe they'll give you an antidepressant, right? Right, right. And of course, those come with side effects. They're addictive. They impair cognition. They have all kinds of long-term effects. I mean,

the benzos or things like Valium and Lorazepam or Ativan, they may lead to increased cognitive problems like dementia when you get older and being you know we heard all the stories about people wandering around doing stuff they shouldn't do in the middle of the night and uh it's it's unfortunate that that uh there are other things too that traditional medicine misses that affect sleep um you talked about the big ones which are the stress and the sleep apnea and the hormonal issues. But there's really more that we know about sleep disruption. And the difference with functional medicine is that we tend to take a detective approach.

We don't just stop at the diagnosis. Insomnia is a symptom. It's not a disease, right? And so we go, oh, I know it's why you can't sleep. You have insomnia. No, that's just the name of it, silly. That's not the cause. And so we kind of have a different approach.

And over the years, there are things we've really uncovered in functional medicine that play a role in sleep that are mostly ignored. And so you shared a little bit about it earlier when we were chatting. But what are the kinds of other things that we see underlying the root causes of insomnia? So if we think about insomnia, about 80% of people who develop chronic insomnia, there's an initial inciting event, but it leads to a stressful event, for example, and there's- Like a death or divorce. Right. Or a transition with the job. And I think the pandemic has contributed to it as well. But then what happens is there's this upregulation of the HPA axis and this chronic overproduction of cortisol,

hypothalamic pituitary adrenal axis. So it's the brain's command center that tells the body what to do. Absolutely. So it's that connection between what our brain is registering as a threat and how that impacts our need to respond to that threat by pumping out these hormones that then in turn keep us ready to deal with a threat that may not be there anymore. So basically, if you're in fight or flight, your job isn't to go take a nap. It is not. It's to stay on alert and wait for the next thing that's going to threaten you. So that activated sympathetic nervous system is huge. And our culture just does that. Absolutely. is huge and our culture just does that but the phone is like a dopamine uh you know a pump

it's like a dopamine pump that keeps your blood pressure up i mean you know what when people are dying in the intensive care unit the drug we give them to keep their heart going is dopamine right and that's what great you know and so like it's like at the very end of life like if you can't if everything else epinephrine fail everything you give dopamine because it's so powerful at keeping you awake and alive and so what everything in our life is the sugar the phones all the new like it's just we're constantly in a dopamine barrage you know it's funny you said that because i've had people tell me, you know, I wake up at 1.30 every night.

I say, well, how do you know it's 1.30? Because I look at my phone and it says 1.30. And that, again, perpetuates the cycle because then you're thinking, oh, it's 1.30. Oh, crap. I'm awake. I should be asleep. And then it just becomes. Yeah.

You know, the best thing I ever did for my sleep issues, because I struggle with them as well, is putting my phone and my watch off. Like just taking everything out and like not knowing what time it is and just letting my body do its thing. I think that's brilliant, Mark. And even sleep trackers for some people, it can be a double-edged sword because you're thinking, okay, what's my tracker show me? How well did I sleep last night? When you get a good night's sleep, it's like the world just looks rosy. And when you don't, it looks depressing. Great. And you know, that's an important thing too. If you pay attention to how you feel. So you mentioned the aura ring. People ask me, how good are these trackers for telling you about your sleep? They don't diagnose a sleep condition, but sometimes you can gain some insights. For you, you gave a great example of this. You found,

oh, look at this one. I've had alcohol. My sleep is not a good. My sleep is not a good. My heart rate, variability, everything. And then you pay attention. Well, how did I feel the day after? Yeah, I was more tired. Yeah, I was more irritable. I was looking for different foods. So I think the more you build that internal awareness of that connection between your sleep and how you feel the next day, that's a win. That's really how you learn to prioritize it. Yeah. Yeah. I just take home here is that sleep is the most underappreciated fourth pillar of lifestyle medicine. I agree. It's diet, exercise, stress reduction, and sleep. And it really is important. and i think i i feel like a lot of my health issues in part were driven by uh lack of sleep and you know i think as doctors

we were just so trained to overcome our natural instinct to sleep when you have to stay up all night alert seeing patients you either pound the coffee or you just will your way through and i remember i remember like working the er and weird shifts like 11 to 2 in the morning and i'd be like seeing patients, you either pound the coffee or you just will your way through. And I remember, I remember like working the ER and weird shifts like 11 to two in the morning. And I'd be like, driving home with like tooth, holding my eyes up like this, forcing myself to not fall asleep. And that just messes with you. When you individualize care and you give people a plan. And I, and I know you've asked me at least three times now, well, what should people do? What I'm trying, why I'm delaying things is because it really truly needs to be individualized. And what we use is a term called the ABCs of Alzheimer's prevention management.

Based on the data, we get data on A's, the B's, and the C's. A stands for anthropometrics. Anthropometrics is basically a fancy A word for body composition. What is your body fat? What is your waist circumference? What is your muscle mass? Depending on these factors, we're going to change the recommendations we give. The B stands for blood-based biomarkers. We're going to look at markers of lipids, cholesterol markers, also advanced markers that preventative cardiologists use, for example, that, you know, most neurologists honestly don't, don't really pay attention to. We look at metabolic markers, insulin resistance. We look at inflammatory markers. We look at nutrition markers, you know, instead of, you know, saying, okay, well go eat fish. It's good for you.

We're going to look at the markers in the blood. We're then going to tell you based on your blood and based on your genetics, how much fish you should be eating what types of fish so so the the take-home point is we're going to get granular with every patient the other thing we do is in the blood-based biomarkers we look at genetics we look at the apo e4 variant it's the most common risk gene doesn't mean you're going to get alzheimer's if you have the variant but it increases your risk well if i know that you have the apo e4 variant they check for this and in 23 and me and millions of people have gotten this checked, I'm going to personalize your care differently. If you have the variant, I'm going to give you plan A, B, and C. If you don't have the variant, I'm going to give you a little bit modified plan, X, Y, and Z.

If you have two copies of the variant, you have a different plan altogether. That's only 1% of the population. So the take-home is we take all these markers and the c is cognitive function and we understand a person's cognitive baseline we look at memory function language abilities learning abilities uh speed of processing attention and executive function which is higher order processing we take all of this and the patient's medical history. We learn about the patient. We learn everything we can about them, about their family, and then we personalize a plan. So those 21 different things are based on that person individually. And you know, there's

a lot of overlap. If you want me to say, okay, well, what are the core things? Well, exercise on a regular basis. Okay. Well, exercise on a regular basis is good but every person gets a different plan if we're putting someone on a plan for body fat loss we're going to give them a different plan steady state cardio for example some people would call that zone two training um steady state cardio at 60 to 65 percent of your heart rate there's different ways to do this through lactate testing through a variety of things that we do you know know, more precisely in our clinic. But we put people on these steady state cardio plans fasted in the morning as long as they can tolerate it because that way it jumpstarts body fat loss.

If we have people that don't do any muscle strength training because they don't like it, we educate them to say, I don't like it either. I'm not, I'm not, you know, Mr. Big Muscles over here, but I have to do strength training once or twice a week minimum, because if you don't have muscles, you can't boost metabolism. So we put people on these very specific plans. High-intensity interval training. I really believe that high-intensity interval training is almost necessary for people with at least one copy of the APOE4 variant. And this is what has been studied now in a couple of studies. And yes, we need more research.

And the studies out of Norway were good. But we need to personalize an exercise plan. We need to personalize a nutrition plan. We need to personalize a vitamin and supplement plan. In some people, we do use drugs. Drugs are actually not commonly used at all in our research, although we do use them on occasion. We'll use a variety of drugs, usually at much lower doses than maybe the regular community uses. But, you know, when it comes to, you know, management, equal opportunity. If there's data and it's relatively safe,

you know, I'll entertain it. So we recommend, you know, cognitive activities that will have a spillover effect. Learning something new, learning how to play a musical instrument, learning a new language. These are things that may have a protective effect, build backup pathways. Believe it or not, even learning how to play a musical instrument in midlife has protective effects on cognitive outcomes in late life. And that's- There's hope for me yet. There's hope for me yet. I got my bass guitar over there. I got blisters on my fingers.

I'm trying to learn to play the guitar. I'm trying, but I just love song. But my big problem is I don't know how to tune it. And I don't, I am so musically inept that I, probably there are good apps and things to do it. There's a website. It's called, you got a pen? It's called YouTube. YouTube, you may have heard of it. I heard of it. Almost as many people watch YouTube as listen to your podcast.

So you can learn how to play guitar on YouTube. I think you can do it. Okay, I'm going to try. For sure. That's my December. Excellent. And January and February and March. So the take-home point is engage your brain.

Treat your brain with respect. Love your brain. Make a plan for your brain. What does that mean? Make a plan for sleep. If you exercise and exercise and exercise, some people say colloquially that that loosens the amyloid, the bad protein that gets built up in the brain of a person with Alzheimer's.

But if you're burning the candle at both ends and you're not sleeping during sleep, especially deep sleep, that's when a person has the trash come. The trash man comes, they pick up the garbage and they take it out and they take it to the trash heap. That is the restorative part of sleep. And if someone isn't sleeping, you know, at least seven, seven and a half, eight hours of sleep is usually the goal. As we get older, it's, you know, harder to sleep that much. But making a plan for sleep,

prioritizing sleep. You know, we have people that track their sleep, that track their exercise. I am wearing a wrist device here. I have nothing to disclose, but we've done several research using this device. I track people on my phone. I have my phone right here and I can check how much exercise they've been doing, how their sleep, how much deep sleep. I can see their blood sugar control. I can see all these different things on my phone because my patients share their data with me.

And when I talk about data sharing, it's not just about tracking sleep. It's not just about doing exercise. It's about tracking it, determining the response, talking to your physician about it. Granted, it's hard to find physicians that will take the time to talk to you about this kind of stuff. Tracking your blood sugar, there's at-home devices called continuous glucose monitors. In our program, we take a very, very deep dive and we learn about all of these different metrics and we refine or fine tune the plan that we give them based on their real time measurements. So, you know,

I can keep going. There's stress modification, you know, transcendental meditation. Bob Roth's taught me a ton about this. What about mindfulness-based stress reduction? You can take a course online. Mindfulness-based stress reduction has amazing outcomes when it comes to brain health. The list goes on and on. There's no one magic pill or one magic cure, but there are a variety of, huh, I was going to say pharmacological and non-pharmacological, but you're reevaluating how I say this now. There are a variety of interventions that are evidence-based and safe that I think all of us need to learn about. Whether we talk about fasting, and I like the term time-restricted eating better, meaning not eating for 12, 14, 16 hours overnight, at least four or five days a week.

I use the term fasting for a more prolonged fast, you know, 24 hours or more, and that's a different discussion. There's the ketogenic diet. There's the Mediterranean-style diet. There's the ketogenic diet. There's a Mediterranean style diet. There's the mind diet. There's components of each diet, green leafy vegetables, wild salmon, grass fed beef, better than non grass fed beef because of the omega threes. There's so many devil is in the details. Half a couple of blueberries and strawberries two to three times a week, you know, leads

to better brain health outcomes and cognitive outcomes in the nurse's health study. You know, many years later on on there's dark cocoa powder there's so many things that i can drop in as as key things but the take-home point is all of these things need to be individualized so let me let me ask you this because i mean you know first i want to just kind of feedback because we i'm listening to you thinking you're a neurologist, but you're also an immunologist, a cardiologist, an endocrinologist, a gastroenterologist, a nutritionist, right? You're breaking down the paradigm of medicine, which is we should stay in our lane, focus on our organ and leave the rest to everybody else. And your insight here is that the body is a system that everything's connected to everything. You can't just pick out one thing and work on that, like amyloid or tau or whatever,

and get to the problem. It's sort of like trying to bail the boat while there's holes in it. You've got to fix the holes. Essentially, the holes that you're talking about are all these ways in which our brain gets injured by our lifestyle and by our environment. And you didn't mention toxins, but that also plays a large role. And so all of a sudden we have to sort of rethink our whole approach, which has really been a reductionist approach, single disease, single drug with a single outcome. And there was an article in JAMA a number of years ago called Shifting

Thinking in Dementia. You probably saw it. And they said in that article that we combine categorical misclassification with etiologic imprecision. And in English, for those listening, that means we categorize dementia according to symptoms, not the causes. And we are not very focused on the etiology or the causes. We're focused on the symptoms. And we say, well, you can't remember this and you fit this profile on your neurocognitive testing. You have Alzheimer's or you have this kind of dementia or Lewy body or blah, blah, blah. And the reality is that you could have 10 people with Alzheimer's who need 10 different treatments. And that's exactly what you're talking about. That's heresy, Richard. That's heresy in medicine, honestly, because we really

have a very, very restricted reductionist view of disease that doesn't let us actually even study these things. And I've literally had arguments with top leading researchers, like heads of research at major institutions saying, these are all the factors that affect the brain we want to study them together so only to study one thing at a time and then see how that works then one thing so study exercise and they say nutrition they study vitamin D they study fish oil I'm like no that's not how things actually work it's like it's like you have to use all the whole picture. The other thing I sort of wanted to sort of touch on was that you're sort of introducing a concept of the personalization, which, again, is very different in medicine.

It's not one size fits all. And you're talking about very sophisticated personalization based on a whole set of biomarkers and tests and things that are easily accessible, but that aren't normally looked at and that aren't normally tested. You know, you get your typical panel, you get your thyroid, your B12, you get your spinal fluid done, you get your MRI and you go, okay, you got Alzheimer's. It's sort of a little bit more complicated than that, but it's really a fairly narrow window of biomarkers and metrics. And there's bazillions of them. And I think we're just sort of touching the sort of tip of the iceberg on this. care around food, around exercise, around sleep, around stress, around supplements,

around everything that you really begin to see dramatic changes in brain function. Yeah. I, you know, I often joke that I'm like a one-third neurologist, but a preventative neurologist at that. I'm a one-third make-believe. I will, full disclosure, I'm not a preventative cardiologist, but I'm a make-believe preventative cardiologist. I'm a one-third primary care doctor and make-believe preventative endocrinologist. I don't even know any preventative endocrinologists. If you find one, introduce them to me. I was trained in an environment. I went to a six-year medical program where I was in med school from day one, University of Missouri, Kansas City. I knew I wanted to be a doctor when I was five, 17 years old, wearing my white coat. And I did so much internal medicine during med school. I had

like an extra year of medicine because that's the way our training was. And I don't know if it was that, or I'm not sure exactly what it was, but Alzheimer's disease is a medical disease. Yeah. Full stop. That's it it there's this thing called the skull and it's a hard thing that protects you when you fall but it's just like it it's like when you have medical conditions you can affect your kidneys when you have medical conditions it can affect your eyes it can affect your heart the same thing it can affect your brain and I couldn't agree with you more

people can take different roads to Alzheimer's and you have to figure out what road they're on and get them the heck off that road. Women, for example, are unfortunately many times in the fast lane to Alzheimer's. Women, two out of every three brains affected by Alzheimer's are women's brains. And five, 10 years ago, I would say I didn't know why. And now I think I can answer that question. And it's related to the perimenopause transition. It's related to specific life factors. It's related to women being maybe a little bit more at risk if they have the APOE4 variant. So the take-home point here is if you understand a person's individual risk factors, whether it's biological sex, whether it's medical conditions,

whether it's what's floating around in their blood, whether it's what is their cognitive function at baseline. You have to figure these things out and then you have to target that plan and personalize that plan. And I mean, Alzheimer's disease and brain health needs to be treated in a medical way. Because if it's not, if you're just targeting amyloid, you're missing the boat. You know, amyloid is a marker. And I think hopefully one day we're going to have just like we treat diabetes with lifestyle interventions and, and exercise and as well as certain targeted drugs that honestly, some of them actually do do tend to work pretty well. I'm not the biggest fan of insulin like that doesn't that's that's maybe band-aiding to

me. That's probably too late. I mean, I'm not the best, whatever, but some of these new, you know, new things that are pretty interesting. I won't get into specifics, but I hope that one day we treat Alzheimer's disease and cognitive decline like any other chronic disease of aging where we hit things with a multimodal evidence based and safe approach that requires a medical intervention. So essentially what you're saying to paraphrase is that Alzheimer's is not a brain disease. Correct. It's a systemic a brain disease. Correct. It's a systemic disease that affects the brain. Yeah, I really believe that. I have to be careful saying that.

Is this being recorded? Yes. And it's going to be broadcast to billions of people around the world. Great. Great. My field. I was just gaining some fans in my field, and now it's all a decade of work. Oh, no, no.

You were at the forefront of a paradigm shift that's happening throughout medicine, which is the breakdown of the old concepts of disease from simply this reductionist organ-based, symptom-based model to systems thinking and network medicine. And that's really all you're talking about. And, you know, you've touched upon some of the most easily accessible and modifiable factors, which is what we eat, how we exercise, how we handle and manage stress, how we sleep. Those four pillars are huge. And then there's the fine tuning with, you know, managing metabolic risk factors or getting their nutrient levels up to a certain level. But there's a whole treasure trove of stuff that we i think still haven't even dug into it's like it's like i i visited ephesus in turkey and it's the largest roman city during the roman empire it was it was incredible it was all buried under dirt and you know rubble and they excavated it but there's they're still figuring they're still you know excavating it 100 years laterated it, but there's, there's still figuring, there's still excavating it a hundred years later. And it's, it's just fascinating to see that there's so

much we don't know. And I would say in my experience as a functional medicine doctor, I've seen things that have impact on the brain that aren't really included, like heavy metals. Do we, do we even have a way of testing that is in conventional medicine for every metal? Not really. We just do a blood test and then we don't worry about it if it's okay. But there may be total body burden of toxins we don't look at. The microbiome is another huge factor that affects the brain in Alzheimer's.

And mitochondrial function is something you talk about, but it's often ignored. And we have latent infections that may be affecting the brain that cause inflammation, whether it's herpes 2, maybe link, but there may be other things. I mean, Chris Gustafsson had Lyme disease and got diagnosed with dementia. There may be environmental factors like mold that have

impact on inflammation. So we know that the brain with patients with dementia is inflamed. And then the causes of that inflammation can be multiple. And so part of the diagnostic dive that you're doing, and I would just sort of encourage you to think about this, is that you're getting to all the stuff that we do know that's so clearly evidence-based, but then there's a whole treasure trove of things to look at that we're kind of ignoring. And I'm just going to take like two seconds. I know it's my podcast, but you're talking, but I'm just going to just talk about this. I know it's your podcast, my podcast, but you're talking, but I'm just going to just talk about this one patient. Cause it just, it was the first patient I had where I'm like, came in the guy with Alzheimer's. I'm like, can you do anything?

I'm like, I have no clue. I don't know, but I'm just going to apply the model of systems of biology and functional medicine. Let's see what we do. We found he was severely insulin resistant. He had, which is, you know, we talk about Alzheimer's as type 3 diabetes in the brain. He had very high homocysteine levels and methylation problems. So his genetics were off around metabolizing B vitamins in the right way, which we know is a risk factor for Alzheimer's. He had the ApoE4 double 4 gene. So he's the 1%. He was seven years old, cognitively impaired, diagnosed with Alzheimer's, basically at home and not able to do anything, depressed,

not functioning. It was the former CEO of his company. He also had other nutritional efficiencies like vitamin D and he had been living in Pittsburgh. And in Pittsburgh, it's the capital of steel. And for a century, they've been burning coal for the steel plants. And they use coal there for the streets on the winter for ice. They put it on the fields for fertilizer and what they do. It's everywhere. And all my patients in Pittsburgh have high mercury levels. And he had very, very, very high mercury levels when we did a challenge test. He just had a mouthful of fillings. And we know that if you look at, you know, amalgam scores, the surface area, and you look at animal studies,

the more amalgams you put in their mouth, the more mercury ends up in their brain. And so I said, well, I don't know. I don't know if anything I'm going to do is going to work, but let's fixure in some resistance. Let's fixure. Also, he had terrible gut issues. He had irritable bowel for 30 years and went on Stelazine for his stomach which is a psychotic anti-psychotic drug to kind of calm his stomach

down and i fixed his stomach i cleaned up his diet fixed the insulin resistance i fixed the b vitamin thing i got rid of the metals and the guy came back to life and it was really really remarkable and he was able to go back to work and function again and be part of his family and be part of his society in a way that I was just shocked. And so I think that, you know, there's a level of stuff that we're looking at and there's a whole bunch of stuff we're not looking at. So I'd love you to comment on that and what your thoughts are about all that other stuff that's going on. Yeah. So, and thanks for sharing the story because, you know, every story is instructive because this is, I'll send you the article that I described as an editorial I wrote for a medical journal.

Because you'll go, wow, you know, this is interesting. So, you know, the thing that resonates with me with the story is, you know, when you have people with ApoE44s, those are just different eggs. And, you know, E44s may be – you know, for example, E4-4s may be preferentially responsive to vitamin D, for example. So, you know, some studies show that vitamin D, eh, maybe it's not really that preventative. Oh, some studies show, oh, maybe it is more preventative. Well, people with two copies of the E4 variant, which is again, not, not super common. Those people really need to have their vitamin Ds up. And that's, and you know, that's, that's just an example there, but you know, people with the ApoE4 variant, you know, pesticides, DDT and DDE, the interaction

between E4 and pesticides increases Alzheimer's risk several fold. If people don't have the APOE4 variant, maybe they're not as exposed, or maybe they're not as increased risk to Alzheimer's. So when you look at a whole population, you don't tease out for E4 positive versus negative, the studies may not show any correlation. But in we see the correlation and in other studies you do see the correlation so i think you know something i was at a conference in in canada you have a lot of fans in canada by the way just just definitely your name came up there um true it's everywhere i mean i'm in istanbul at the airport and some guy from the security comes running up to me. I thought I like was going to get arrested for smuggling something.

I got smuggling my Turkish delights back to America. And he's like, Dr. Hyman, can I take a picture with you? And I'm like, oh, fine. Okay. International. So I was at this thing in Canada and amazing people, just smart people. And, you know, we were giving presentations. And, of course, I'm like, you know, the science guy.

And I'm like a clinician. I'm like a regular doctor. I don't want to say Joe Schmo like you and me. But, like, you know, I was thrown into this clinical research thing. And, again, I had resources, infrastructure, did work hard to learn, hired the right people. So, yes, I've done research. And when you do research, you need to have objective measures to follow that you can track. I was at this group in Canada, this guy named Gary and Elizabeth. Elizabeth's a naturopathic doctor and Gary is just really, really, really smart. And they were

working together to present on a topic. And it's kind of like a bulb light bulb came off my head. And I said, you know, I'm so focused in the objective because I need to be, cause I'm a researcher. If I'm going to say something and think it, I need to then prove it. Cause if I'm in an academic environment, you know, I was at wild Cornell medicine for a New York Presbyterian for, you know, almost eight, nine years. And now I'm at Florida Atlantic university doing a really, a really exciting program in brain health and Alzheimer's prevention,

Parkinson's prevention, dementia with Lewy body prevention. I get to do some really cool things. Maybe I'm missing the boat a little bit because if I'm just focusing on the objective that I need to track and prove, there's a lot of stuff under the surface that I can't really track and prove because I don't have a biomarker to do that. So I guess what I'm trying to say is, I know what I know and I don't know what I don't know. I'm consciously incompetent about things. And the story that you say is, yeah, no, I am,

there are people that are unconsciously incompetent and those people drive me a little bit batty, but I am- I'm with you, I'm on your team. I'm on the, I know what I don't i'm on the i know what i don't know yeah i know what i don't know and and i'm i'm willing to have my eyes opened and um you know the stories that you say it's like as a physician you you have to treat someone in a certain way to try to make them better but we don't always have all the objective you know evidence and and the types of work that we do on patients, it's really hard to study. Like I have empathy for people, you know, in our boat who are trying

to study the rigorous, you know, rigorously study because what's moving the needle to me, I don't care what's moving the needle. People were criticizing, you know, one of my research paper. Oh, you recommended 21 things. What if 18 of them are helping and three of them are harming? You'll never know. And I said, okay, but but but look at the results 18 months later people with amyloid in their brain with mild cognitive impairment due to alzheimer's disease that followed this plan 18 months later the long as they followed 60 or more of what i recommended had better cognitive outcomes 18 months later we were able to improve. There's no drug that can improve symptoms. Slowing decline is one thing, improving symptoms. So I'm zen with not being able to

precisely understand which of my 21 things are working. But I think as clinicians, I think we just have to do the best we can. And we want to, you know, promise not to over promise. I think that's important to you. You said at the beginning, when you were seeing that that patient, I'm not 100% sure, you know, yada, yada, but I'm going to try all the usual things. And you know, something worked. So I think as long as we have honest conversations with our patients, and, and, and do the best, you know, people like us that have academic appointments and are in that, you know, realm, I think we it's, it's, you know, people like us that have academic appointments and are in that, you know, realm. I think we, it's, you know, it's my duty in some ways at this time in my life,

in my career to try to prove as much as I can. But I think, I think the field, and I think people need to realize that some things are really hard to study and prove. I hope you enjoyed today's episode. One of the best ways you can support this podcast is by leaving us a rating and review below. Until next time, thanks for tuning in. Hey everybody, it's Dr. Hyman. Thanks for tuning into The Doctor's Pharmacy. I hope you're loving this podcast.

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