The Longevity Solution - with Dr. James DiNicolantonio | The Empowering Neurologist EP. 83

Well, hello everyone. Welcome again to The Empowering Neurologist. I'm Dr. David Perlmutter. We all want to live a long, healthy life, and fortunately, we are now seeing a robust science being developed that really allows us to understand The mechanisms by which certain lifestyle choices are indeed associated with better outcome as it relates to not only the length of our lives but the quality of our lives. And today we're going to explore that. My guest is Dr. James D. Nicolantonio. Many of you have probably seen his podcast. We've interviewed him before, and here is his new book, *The Longevity Solution*. Let me tell you a little bit about Dr. D. Nicolantonio. He is a pharmacist in cardiovascular research and a Doctor of Pharmacy at St. Luke's Mid-America Heart Institute, which is located in Kansas City, Missouri. He's very well respected. He's internationally known in terms of his scientific publications, and he is really a very sought-after expert when it comes to health and nutrition. He has contributed extensively to health policy has even testified in front of the Canadian Senate regarding the harms— who knew— of added sugars. He serves as the associate editor of British medical journals BMJ, Open Heart, a journal published in partnership with British Cardiovascular Society, and impressively, he's the author or co-author of approximately 200 scientific studies that appear in the medical literature. He's also the author of 2 bestselling books, The Salt Fix and Super Fuel, which we've talked about before. He is also on the editorial advisory board of several other medical journals, and he will join us today to talk about his new book that he wrote along with Dr. Jason Fung that we've also interviewed in the past as well. He's going to join us to talk about how our lifestyle choices affect For example, the expression of longevity genes, various aspects of our day-to-day decision-making as it relates to the types of foods that we consume, how much protein we should take in, exercise, etc., and how these all relate to longevity. So here we go. Welcome, Dr. DiNicolantonio.

Thanks for having me.

In your book, the subtitle that we, we The subtitle of your book, which you wrote about in the entry blog, says Rediscovering Centuries-Old Secrets to a Healthy Long Life. You know, we live in a time when we're looking at the latest, greatest science. How did that come to be the subtitle of your book?

So, you know, really, I mean, you're trying to look at populations that, you know, traditionally always been healthy, had long lifestyles. So take the Mediterranean diet, for example. High in omega-3s. They do drink fair amounts of coffee. They consume moderate amounts of red wine with their dinner. We're trying to look at populations that have always had these ancient secrets and sort of like what your grandmother has always told you. I know it sounds simple, but we wanted to kind of integrate these easy tools to help promote longevity.

I have a smile. My grandmother used to tell me some pretty wacky things, so I'm not sure— I think you meant you and the— In the broader sense. We talk about then the Blue Zones around the world where people in— where populations in general seem to have a longer lifespan. What goes on in these places that we should learn from?

I think, traditionally, if you're looking at the typical US diet, it's fairly high in animal protein and not too high in plant protein. And very low in antioxidants. So I mean, the typical American, most of their antioxidants are coming from coffee. Unfortunately, most Americans' coffee is loaded with heavy cream and sugar, so they're not necessarily reaping the benefits that a lot of people could be if they're consuming coffee with maybe just some light pastured cream without the sugar. But traditionally, what you see is just, you know, moderate protein intake, definitely more plant-based. But, you know, Dr. Fung and I provide a solution that really brings together the benefits of both animal protein and plant protein and how to combine it. We're definitely not recommending a low protein diet. It's more protein cycling to match what evolutionarily we would have consumed as hunter-gatherers.

What does that mean, cycling?

Basically, I mean, when I was doing research for the book, if you look at even current-day hunter-gatherer tribes, what they do is during a hunt, They will consume plants. So they're eating a fairly low protein, more higher plant diet until they actually, you know, kill the bison or kill the antelope. Then all of a sudden they're eating a high protein, high animal protein diet. And so if you can kind of mimic that, when you can go periods of higher protein to build muscle and then periods where you're not working out, a more lower protein diet, you're activating autophagy and then you're also activating— Growth. Muscle growth and mTOR when you're eating a higher protein diet. You're building yourself up to only break yourself down again and renew yourself. That's really the strategy and the key to protein intake.

All right. Let's, for our viewers, unpack what mTOR is and why it's really the focal point in the discussions these days with reference to the amount of protein we consume. Let's really go into detail as to what mTOR is. Yeah,

so it's called mechanistic target of rapamycin, and basically it's an ancient nutrient sensor that spans all life forms and goes all the way up to humans. Its counterpart is called AMPK, and it's another nutrient sensor. Basically, mTOR is an activation of growth. If you are eating a high animal protein diet and you're working out, you want to activate mTOR. You want to build muscle. But in the same token, when you are growing, you are not repairing. So there's a trade-off. So when you are constantly have high mTOR, you are in a state of growth, but that can be potentially pro-cancerous. You don't want growth all the time. And then on the flip side, you have AMPK, which is an enzyme but also a nutrient sensor, which is activated during periods of energy deficiency. So either fasting, exercise, And we— what's really cool in the book, we give secrets how you can activate AMPK besides just fasting or besides just exercise, which actually probably is the strongest activator of AMPK. And AMPK is what activates autophagy. It's what— autophagy is self-eating. It's where you basically break down old cells and regenerate new cells. So we provide tools, dietary strategies that can actually activate that AMPK as well.

All right, so now we're going to shift over to autophagy. Auto meaning self, phagy meaning to eat. And exactly what is this and why should we think that it's something important that we would like to enhance?

So it's again this ancient nutrient sensor, and when you can activate autophagy, not only can you activate this ancient ability of your self-repair, But it actually turns on mitochondrial biogenesis. So it allows you to regrow the mitochondria that gives yourself energy. So people who are suffering from energy, they may literally not have the same amount of mitochondria or functioning mitochondria as you and I. And so tapping into this ancient nutrient sensor can allow people to not only, again, repair their own damaged cells, but grow new mitochondria and enhance the energy production of their own self.

Now, we've talked on this program quite a lot over the years, I'm sure our viewers will agree, about what's called the ketogenic diet, and I think more broadly about getting into ketosis and how that is brought about by calorie restriction, and these days being able to create ketone bodies, ketone chemicals in our bodies, even without necessarily calorie restriction. You call calorie restriction in your book a double-edged sword. Can you walk us through that?

Yeah, basically, 99% of people who are told to just eat less, they can't follow that type of diet. They simply— the hunger hormones and their own hormones themselves, you go into this basically fat-storing famine mode, which is not what you want. Basically, for every calorie you eat on a chronic low-calorie diet, You're storing more fat. So there's a way to eat less calories but not reduce your, you know, basal metabolic rate, and that is through time-restricted feeding or intermittent fasting, where you cut your eating window down. So the typical fast is 12 hours. You go to bed at 8 o'clock at night, you wake up at 8 in the morning. That's what typically, you know, most people do. But if you want to really start activating autophagy, you got to start digging into the 16, 18-hour, 24-hour fasts. So if you can skip breakfast and go maybe eat lunch at noon, now you've hit a 16-hour fast, and now you are— your eating window is now down to only 8 hours. And so you may actually eat the same amount of calories, but you're eating it in a shorter window, and now your muscle cells are more sensitive to insulin, and you are actually able to utilize those calories better and burn them better had you— versus eating them throughout the day, those— the same amount of calories throughout the day.

So there's a really terrific book called The Circadian Code by Dr. Panteth, and we are— we're going to reach out to him to have him on the program. But, you know, he makes it very clear that every cell in our bodies, including our bacterial cells, are really dialed into this circadian code, and that we should eat, as you mentioned, within a window, a time restriction of sorts. And how that tends then to line up the various metabolic activities that deal with harnessing energy from food and nutrients, etc., with our basic chronobiology. In our discussion of protein, you had mentioned— I think you were tending towards more of a plant-based protein. What are the differences in terms of what we can expect if we favor plant versus animal protein?

Yeah, I mean, I was confused before I started writing the book. I mean, myself, I was confused on should I be eating a high protein diet or low protein diet? Should it mostly be coming from plants? You know, Dr. Fung and I landed on really a 50/50 split, but some people are going to benefit more from animal protein if their genetics are more geared towards eating more animals. So if you are from an area of more northern latitude, you likely ate less plants and ate more animals. Um, but if you I mean, in general, most hunter-gatherers were consuming anywhere between 35% and 65% of their calories from plants, which if you average it out, it ends up being around a 50/50 split. But there are significant differences, and the reason why I believe it's best to integrate some of both is, number one, in the 21st century, animal fats are what store persistent organic pollutants. It's just something we have to deal with. So the, the, the eggs, the, the fat from the, you know, your steak, it's going to contain these persistent organic pollutants like PCBs, dioxins. The only way to bind those naturally is plant fiber. So there's an important integration between plants and animals that we've always had, um, that if we can match and mimic, that we can kind of, kind of mitigate these risks. And the problem with these persistent organic pollutants is exactly that. They are persistent. Right. Some of their half-lives are over 10 years in the body, and we have no real good way of getting rid of it. So there is this type of enterohepatic recycling of these persistent organic pollutants. So when you fast, you push them out of your own fat stores, and they can cause a lot of damage. But if you combine them in the GI tract with plant fiber, you can slowly excrete them out. So not to mention, plant fiber is very good with the resistant starch to feed your own good gut bacteria. So There's benefits of integrating both, which I hope we revealed pretty well in the book.

Well, I think you did an excellent job, and I think that it was very well balanced. Getting— you mentioned fasting, and I have to admit, every interview that I do these days, that's a question, either the one or two, first or second question I'm asked, what about fasting? And you actually dedicate a chapter to fasting. Tell us what your thoughts are. Maybe define what it means and why it may be something we should consider.

Yeah, so typically you have your intermittent fasting, which generally is about— most people do a 16:8, which is 16 hours of fasting and their window of eating is 8 hours. Then some people go out to 24 hours, and then extended fasting is considered beyond 24 hours. Some people start doing extended fasts maybe once a month. Some people do it maybe even up to twice a week where they're fasting 24 or 36 hours once or twice a week. Really, it depends on the person. If you're going extended periods, generally you want to be monitored by a doctor simply because some people are damaged enough where they can't even hold on to the minerals from their kidneys. They just spill out in the urine. You have to be careful with certain individuals. Fasting, a lot of people, the main concern with fasting is the depletion in blood volume. So you get very dizzy because you keep spilling salt out the urine. And so everybody does a water fast, but I try to tell people it's very important to integrate salt when you're fasting simply because your kidneys do not shut off the salt loss because your insulin is so low when you're fasting. Insulin is what helps the kidneys lock the salt in your body. A full teaspoon of salt when people are fasting each day can really help mitigate the dizziness and the side effects.

Tell everybody why you know so much about salt.

Well, I mean, as you know, you endorsed my first book, The Salt Fix, so yeah.

There you go. I want to just segue from the discussion on fasting, which is in fact keto production. It's a form of achieving ketosis. Ketosis, that we see that in the ketogenic diet in general. Because not only, you know, are you experiencing these effects from insulin, but in addition, you're creating ketone bodies which act as— in a colligative way to ultimately lead to more of a diuresis. You're losing fluid, you're losing water, which takes along with it as you increase this water loss, though you're repleting water, salt. And not only that sodium chloride, but also magnesium as well, so, and potassium. Yeah. So, you know, one of the things that I think is really very important, one of the pushbacks from a ketogenic diet has always been, gosh, like you say, I felt dizzy, I felt weak, my blood pressure was low. And I think second to constipation from lack of adequate amounts of dietary fiber on a ketogenic diet, this hypotension and feeling unwell from low blood pressure is very common, and people can just— if you're careful with salt and magnesium, and there are products out now that are specifically designed to help people with that, it makes it, you know, you can get through it and maintain your blood pressure and feel well. You then in the book go to some specifics Talking about things like coffee and tea and red wine. Why don't we first start with tea?

Yeah. Even taking a step back, when we were going through the theories of aging and what we think causes aging, we used to think it was this overproduction of reactive oxygen species and not having enough antioxidants. As I started learning how antioxidants work, and even your new Updated edition of Grain Brain touches on this, which I loved, by the way.

Thank you.

Is that some of these antioxidants actually work through actually giving you a little bit of oxidative stress, upregulating your own endogenous antioxidant systems. So, you know, when omega-3s oxidize in the body, as you covered, it activates NRF2 and activates your own antioxidant enzyme system. So we kind of had it wrong. In the sense that we were thinking antioxidants were beneficial by scavenging these reactive oxygen species, when in reality, it's— they give you a little bit of damage and upregulate your own endogenous antioxidant systems. And so, we landed on the best theory for preventing aging is hormesis. How can you give yourself a low dose of harm to make your cells that much more stronger to the next insult? And so, really, all these things, green tea, coffee, red wine, They give you a little bit of damage. The polyphenols actually upregulate your own antioxidant systems through this type of, you know, the catechins and the things in the polyphenols literally primarily work through their, like I said, the hormesis effect. So green tea is interesting because a lot of people consume green tea wrong. They add milk, which binds the catechins and makes basically green tea completely ineffective. If you're going to consume green tea, you should not really be adding dairy to it, but for coffee, you can get away with that. The polyphenols in coffee aren't bound by dairy. That was just a quick tip that people can take to the bank.

Go ahead.

I'm sorry. Green tea is unique. It's been consumed in Asian cultures for thousands of years. Some people— it's more Consume that more later in the day, whereas I like to consume coffee obviously more early in the day because it has higher caffeine intake. But really, to reap the benefits of green tea, you either have to have an enriched, like EGCG type of green tea, or you have to be literally drinking green tea throughout the entire day like they do in most Asian cultures. 1 or 2 cups of green tea really isn't going to give you the optimal benefits of drinking that type of beverage.

Well, you mentioned you're a coffee drinker, and what are the benefits from that?

Yeah, so coffee is unique because, again, it actually depends on your own gut microbiome, which is so cool. Your gut microbiome takes the chlorogenic acid in coffee, converts it to caffeic acid, and then your liver converts that to ferulic acid, which is the most— one of the most potent antioxidants. It's been shown to prevent ischemic reperfusion injury in animals. And so coffee, like we touched on before, is the largest source of antioxidants for most So if you can just consume coffee with maybe a little bit of cream, just maybe a little sugar if you're going to add any type of sweetener, but you don't want to, you know, obviously you don't want to overdo it, then you can start reaping the benefits of coffee. And both green tea and coffee have these nutrients inside of them that activate AMPK. So the diterpenes in coffee and the caffeic acid can activate AMPK. Now AMPK not only is the longevity enzyme, but it increases your own fat burning. It also lowers blood sugar. That's what metformin does. Metformin is basically just an AMPK activator.

Now, you had an interesting graph in your book that looked at alcohol consumption versus— plotted against, I think it was all-cause mortality. It was a U-shaped curve. Maybe you could walk us through what that means.

Yeah. Basically, a U-shaped curve It happens even with salt. It happens with any mineral as well, or really any dietary nutrient. If you're not getting enough, you're at a very high end of mortality, and then there's a sweet spot where mortality drops at the perfect point, and then you go up where mortality starts increasing if you overdo it. You see the same curve with salt. You see the same curve with red wine. Basically, the optimal dose of red wine is probably a lot less than what most people think. I think a lot of people think they should be consuming 2 or 3 glasses, Really, what the best data shows is really around 6 ounces of red wine for a man and around 3 ounces of red wine for a woman with the largest meal of the day on a daily basis seems to be associated with the lowest risk of mortality.

I think some of us have some work to do, not drinking enough based upon the U-shaped curve.

Yes.

I just want to explore that for just another moment, and that is I am guilty of Thinking if something is good, more is better. If restricting something is good, then ending it completely is better. And we recently reviewed a study. I think I did a podcast on it, looking at fasting insulin levels. And you know, we always tend to think lower insulin levels the better. But this was an interesting report out of Sweden that actually did demonstrate that really low levels of insulin were associated. 2 decades later with increased risk of dementia. I want to get back to this notion of animal versus plant-based protein. There is some concern in those who favor plant-based protein that they're not getting complete protein. How do you address that?

Yeah, so I mean, if you're typically— you're referring to just someone maybe eating rice and not mixing it with beans or other types of— or peas or other types of sources of plants. So you're correct. And that, you know, if you just eat one source of plant protein, you definitely can potentially not be getting all the essential amino acids. So the typical rice and beans is your way to kind of combat that. And of course, you know, animal protein is more bioavailable. And so, you know, you can fall at risk of not getting enough protein if you're, you know, fully consuming just plants. So it is important, I think, to integrate both, not from just a protein perspective, but Also, unless you're consuming chlorella, which in my mind is really one of the only plant sources of active B12, you're going to be lacking in vitamin B12, which is important for cognitive health too. I really tend to— you have vegan and you have carnivore, and I'm trying to get people to understand it's somewhere in between that's likely the optimal diet.

What you did do in the book is you threw a very large net. You were very inclusive and embracing of people from all parts of the spectrum, from veganism to full carnivore. I want to let our viewers know that in our next book, which is called Brainwash, we've really moved towards more of a plant-based diet, again, trying to be very inclusive. But I think not just from the perspective of the individual and his or her health, But I really do believe that there's pretty compelling evidence that planetary health would benefit from more of a plant-based diet. Not saying, you know, that we don't embrace the idea of some animal-based products, like, like you said, James, but— Mm-hmm. And where we are on that project is we have a landing page, which is brainwashbook.com. Just— that's— the book's almost completed, but for people who want to learn about it, that's all. That's all that's up there, but you can see that. I'd like to get to, I think, a very important topic that you covered that virtually every nutrition-based book these days is a must-look at, and that is this delineation between what makes for a good fat versus a bad fat. Why don't— let's unpack that a little bit.

Yeah. I think, I mean, through your books and obviously our other colleagues' books, people are starting to realize that saturated fat may not be as bad as it used to be. But I think somewhat what's getting lost too in the messaging is saturated fat's okay, but it's not a super fuel type of super fat. Those type of fats are more of your marine omega-3s, your plant-based omega-3s, even some plant-based omega-6 fats too. Your MCTs, your medium— your coconut fats seem to be on the healthiest end of the spectrum. Saturated's kind of in the middle, and then the harmful fats are really your animal fats. Right. Industrial vegetable oils, which are high in omega-6, and your trans fats.

Why are these oils that line the grocery store shelves— safflower, corn, sunflower oil, soy oil— why are they so dangerous for us?

When you think about it, we've never consumed them ever until we developed multi-million-dollar machinery to be able to extract them from these seeds. They're supposed to be protected by a seed or a nut, a coating to protect these susceptible oils from oxidizing, and nature packaged them with vitamin E to prevent them from oxidizing. So when we push it out with high heat, pressure, hexane, with these machinery to produce just an isolated high omega-6 oil, the oil's already oxidized. Even if you get a cold-pressed canola, 5% of that oil is going to have trans fats already in it through the oxidation process, and then your body— then you consume it, your own stomach acid starts Oxidizing, again, this oil that's completely lacking of any vitamins or minerals or any protective coating from preventing it from oxidizing. The balance, too, of omega-6 and omega-3 is lost from when we used to consume more omega-3. These oils are 20:1 or 6, sometimes 100:1 omega-6 in favor versus omega-3.

The standard American diet is one that favors and demonstrates an omega-6 to omega-3 ratio of somewhere around Yeah. What would you say would be more appropriate?

More of around a 4 to 1 at most favoring omega-6 to omega-3. Really, I mean, the reason why a lot of these omega-3 studies didn't show benefit was because you're trying to give a 1 gram dose of fish oil in someone who's consuming 30 grams of omega-6. When they finally did a study that tested 4 grams of fish oil, they found a dramatic reduction in cardiovascular events. You just need to make sure you're getting the right dose of omega-3s.

How is it that these omega-6s actually ultimately lead mechanistically? How do they turn on inflammation?

One of the biggest offenders is there's a metabolite, an aldehyde that is formed when your body oxidizes these oils called 4-HNE, 4-hydroxynonenal. It's a big word, but basically this type of aldehyde forms what are these lip oxidation end products. So everyone knows advanced glycation end products from sugars binding to proteins, but this is fat binding to proteins, and these can lead to neurofibrillary tangles that we see in Alzheimer's patients. And this 4-hydroxynonenal is extremely reactive, and there's all these other oxidized linoleic acid metabolites Linoleic acid being that omega-6 fat that gets metabolized that just causes widespread inflammation. I think it is even much more harmful than eating sugar by far.

What we're also seeing these days is the apparent omega-6 arachidonic acid actually is the precursor from which 2 of the endocannabinoids are formed, 2-AG and anandamide. which then go on to stimulate a particular receptor on fat cells.

Yes.

CB1 receptor, and that dramatically increases the production of these pro-inflammatory chemicals. You can block that whole pathway by supplying endocannabinoids that happen to be derived from the omega-3s. So that's another interesting, and I think newly discovered, a pathway by which we really want to focus on, you know, leveraging the power of these omega-3s in ratio to these omega-6s in terms of gaining a foothold on this powerful mechanism of inflammation that underlies virtually every disease you don't want to get. So at the end of your book, you have a really great program. Just if you can do the broad strokes for that, for our viewers.

Yeah, so number one would be, you know, cycling your protein intake. Trying to bring on more plant protein too and match that. Fasting—

Right off the bat, that's kind of a unique thing to your program.

Yeah.

Yeah, increasing animal or plant-based protein is a good thing. We've heard quite a few people talk about it, but I think it's the, the cycling of the protein that really was unique to your book.

Yes. Yep. And really, that goes along with the intermittent fasting too, as one of our 5-step plans, because, you know, most people are snacking 6 times a day now, and you're not giving your body time to heal and time to upregulate autophagy and activate insulin sensitivity so your body can burn— start burning its own fat.

Let me stop you just for our viewers. What Dr. DiNicolantonio just said is we really need to turn on this process of autophagy where our bodies are able to, number one, recognize, and number two, get rid of cells that are damaged. By the same— at the same time, we want to also be engaged in something called mitophagy, which happens with fasting, and that is to identify and rid our bodies of damaged mitochondria. Mitochondria tend to, when they are damaged in terms of a genetic perspective, their DNA being unique from your cellular DNA, they replicate those damaged mitochondria, and this is a way of identifying them and allowing fresh new mitochondria to be produced to allow your body to energize itself. I apologize for interrupting, but that thought came to mind. No. Because I had coffee this morning. Go ahead.

Yeah, well, that's another step. So coffee and red wine is another step of our 5-step plan, green tea being another one, and then salt and magnesium being, being the 5th.

Great. Well, I want to read to our viewers, uh, my comment on the back of your book. I got to put on my glasses for this. What can I tell you? I'm aging. The Longevity Solution empowers the reader with an action plan for lifestyle modifications That will open the door to preserving and extending health. While deeply rooted in our most advanced science, the prescriptive this book provides is something anyone and everyone can and should embrace. And by that, I meant that, you know, you, you've done an incredible job in looking at the very latest science, but also an incredible job in terms of taking that powerful and complicated science and making it user-friendly and something that virtually everybody can get their arms around. So kudos to you guys, you did a great job.

Thank you so much, I appreciate that.

Great. Well, I hope we get a chance to talk soon.

Okay, me too.

Bye for now. Well, that was a really interesting discussion, and what I like most about it is the fact that we were given so many take-home messages in terms of what we can be doing that really have good scientific underpinning in terms of extending not only our lifespan but our healthspan. Here's the book, The Longevity Solution. I don't know if all the books come with it, but mine came with this handy bookmark, which I love. I love having a bookmark. I love using highlighter pens. So terrific book, The Longevity Solution. Thank you. Dr. DeNicolantonio, really terrific information. And again, thank you all for joining us on our program, The Empowering Neurologist. We'll be back soon. Bye for now.