Revealing New Connections Between Nutrition and Health - Dr. David Perlmutter, Neurologist and Bestselling Author

Shiv Gaglani: Hi, I'm Shiv Gaglani, and today on Raise the Line, I'm very happy to welcome Dr. David Perlmutter, a board-certified neurologist and six-time New York Times bestselling author of books about the connection between nutrition and major diseases, brain health, and stress, among many other health and lifestyle concerns.

You may be most familiar with his book Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar. His latest book, Drop Acid, focuses on the pivotal role of uric acid and metabolic diseases. He's recognized internationally as a leader in the field of nutritional influences and neurological disorders, and is a member of the editorial board for the Journal of Alzheimer's Disease.

He's also a guest lecturer at top universities, and serves as an associate professor at one of our partner institutions, the University of Miami Miller School of Medicine. Dr. Perlmutter, thanks for taking the time to be with us today.

Dr. David Perlmutter: Shiv, I'm delighted to spend time with you today. Thank you for having me.

Shiv Gaglani: As you know, our audience is primarily current and future healthcare professionals. At one point, you were a future healthcare professional, a medical student. Could you tell our audience what first got you interested in medicine, particularly neurology?

Dr. David Perlmutter: I began my interaction with the world of medicine at a very early age. My father was a neurosurgeon at the University of Miami. He was their first chief of neurosurgery back in the day. He was a very busy individual. And I learned early on that if I was going to spend any time with my dad, it was going to be on his time. I convinced him first to take me on rounds on Saturday morning when he would see patients and then ultimately, when I turned around 13 or 14, he invited me to spend time in the operating room with him.

In those days, I guess there wasn't as much concern about that, and I would hold retractors while he would take out brain tumors, and work on somebody's back, taking out a disc. I had a very early exposure to medicine in general and specifically the neurosciences.

In college, I spent a summer working in a lab doing research in Gainesville, Florida, at the University of Florida writing a paper about the anatomy of the brain as revealed by the operating microscope. We ultimately published an atlas to allow brain surgeons to go through the brain and understand it through a microscope, as opposed to just looking at it without any magnification.

Thereafter, I went to medical school and did a neurology residency, then went into practice in neurology. Then over the years, I became less enthusiastic about my job. I realized that as a neurologist, we were treating symptoms, but we weren't treating underlying problems. We were helping people manage their headache pain, or the tremor of Parkinson's, or giving them seizure medication to reduce their seizure frequencies. But as it relates to the big things that we as neurologists deal with—Alzheimer's for example—we weren't looking at why people have this problem.

To this day, we do not have any meaningful pharmaceutical treatment for that disease affecting six million of us Americans. I set about to try to determine what are the inroads to that situation, Alzheimer's per se. Even way back then, I learned that already people were writing papers and doing research indicating that our lifestyle choices play a very significant role in determining the brain's destiny as it relates to functionality, and as it relates to disease risk.

I became very interested in these factors, many of which as you mentioned in the setup are nutritional. Again, I scoured the literature and found out that a lot of people around the world were doing some innovative work, and interventional trials and demonstrating that changes in the diet could have a direct bearing on charting the brain's destiny.

After incorporating these kinds of ideas, as well as other lifestyle ideas -- like the importance of physical exercise, getting enough restorative sleep, etcetera, into my practice -- and not only feeling good about preventing disease but actually seeing that these interventions seem to be helpful in terms of treating the very illnesses that we were trying to prevent, I decided to write a book about it. That was published in 2013. That was Grain Brain, making the simple claim that higher levels of sugar and refined carbohydrates were bad for the brain in terms of its destiny.

That book hit a note. It ended up being published in 34 languages around the world, and a lot of people took notice. A lot of the mainstream tended to castigate it at first. But ultimately, I think the literature verified our contention. That book seems to have stood the test of time.

I then began to dig much deeper into the inroads to metabolic dysfunction. What causes elevation of blood sugar? What causes hypertension? What causes obesity, or at least overweight and elevated BMI? Why? Because they affect the brain and realizing it's not just the brain. It's the heart. It's the immune system. It's a risk for diabetes. It's a risk for even in certain forms of cancer -- colon cancer, breast cancer, and pancreatic cancer.

My journey took me deeper and deeper into what is influencing these fundamental mechanisms like inflammation, which is quite amplified when people are metabolically distressed. That led me to consider that perhaps the gut bacteria might be playing a role.

At that point, we're beginning to see literature that talked about dysbiosis or changes in the gut bacteria being related to our pervasive, chronic degenerative conditions, like diabetes and heart disease. But more importantly, being related to the mechanisms -- like inflammation and oxidative stress -- that are known to underlie these diseases.

I began exploring that quite aggressively and wrote a book called Brain Maker that looked at the relationship between things going on in the gut and a very distant, seemingly disparate organ, the brain. Somehow there was a relationship between the gut and the brain. Who knew? I mean, in our education, the gut and brain were as far apart as Miami and Chicago. But there was never a discussion of any relationship of seemingly disparate body systems in those days. That was early on in the microbiome exploration that, as you well know, followed thereafter.

I began to understand along with another medical doctor -- Austin Perlmutter, our son -- that it was important to give people updated information...great, meaningful scientifically validated, clinically validated information about what they could do to improve their health. It began to be puzzling to both of us that the biggest breakdown of the system of doctors learning information and purveying that information to their patients, was the missing step three: the action on the part of the patient to carry out the information that they were provided.

We realized that there's a lot that affects an individual's decision-making. Whereas we know what the best decision is, we can't bring ourselves to exercise each day, to cut back on the fructose consumption, to cut back on alcohol consumption, to make sure we go to bed at nine or nine-thirty, and that we don't eat too late -- all the things that we talk about that are important. While it's great to make the recommendations, that important part three -- making the decision and carrying it out -- was the breakdown. We realized that about 75 percent of the information that patients are given from their doctors is not acted upon.

We began a deep exploration as to what's involved in making decisions and we distilled that question down to reveal two important areas of the brain that are involved in how we choose to do what the doctor tells us to do or not, but really how we make any decision. To simplify, there is an impulsive non-forward-thinking, nonempathetic thinking, narcissistic part of the brain called the amygdala. It does what I want to do right now, and I'm going to do it, and I don't care how it affects me, or how it affects my future, or importantly these days, how it affects other people.

In addition, there's another part of the brain called the prefrontal cortex that lives behind the forehead. That part of the brain may be called, perhaps, the adult in the room. That's a part of the brain that leverages data, that leverages past experience, that considers multiple possible outcomes, that considers how my decision might affect me, of course, but my future me as well, and might even affect other people and even affect the planet. Again, the adult in the room.

Importantly, we learned that this prefrontal cortex exercises top-down control over the more impulsive, immature amygdala running the show. We call this top-down control. There's a connection between the two called the anterior cingulate.

We rely on having an adult in the room if we're going to make better decisions, if we're going to even do the things or some of the things that our doctors tell us to do. That's important for us to understand as healthcare providers, because you give people the very best information, the printout, you call them the next day, but again, 75% of the information is not going to be acted on.

We distilled down this paradigm as it relates to decision-making and recognized that the connection that is so important to allow the adult to stay in the room is highly influenced and degraded by the mechanism of inflammation. When we augment inflammation in our bodies, we take the adult out of the room and make poor decisions. Why that matters, is because those poor decisions then enhance inflammation and as such, bode poorly for future decision making.

We coined the term disconnection syndrome as to these individuals who, through no fault of their own, cannot carry out the recommendations. That's very important because we write these books, we do the lectures, we interface with the public at so many levels and we've got to recognize that as we move forward in time -- and as more and more people adopt a western/pro-inflammatory diet globally -- their decision-making is affected. Even the way they see the world around them is nuanced by the changes in the setup, in the functionality of their brains, by virtue of this inflammation brought upon them by the very lifestyle choices that we're doing our very best to avoid or allow people to avoid. That took us through Brain Washing.

With the new book, Drop Acid, everything for me is about metabolism, and the downstream negative consequences of poor metabolism are: increased oxidative stress, increased inflammation, elevation of blood sugar, elevation of insulin resistance, blood pressure, and body mass index -- all the things that contribute to the global pandemic that we are now experiencing, the number one cause of death on our planet which is the chronic degenerative conditions according to the World Health Organization.

These are at their core the manifestation of disrupted metabolism. For me as a physician and certainly for me as a neurologist, knowing that there are new inputs that can be leveraged to bring about better metabolic health is always going to be important. That was the state of mind I was in when one day I was going for a run and listening to a podcast where the interview was with a physician, Dr. Richard Johnson, one of the world's top researchers in terms of the role of uric acid elevation in creating metabolic mayhem.

I was captivated by his interview such that I doubled my run that day so I could hear it twice and did what I guess any of us would do when I finally got home and grabbed a shower. I picked up the phone, and called and I said "Hey, just heard this podcast. Unbelievable, and I need to learn as much as I can about uric acid." We spent a lot of time on the phone. We talked about guitars that we played. We talked about metabolism, renal disease, uric acid, diabetes, hypertension.

At that point, I realized I needed to know everything I could about uric acid. I ended up pulling about 500 peer-reviewed references, and learned an awful lot about uric acid well beyond what I had been schooled in, which was simply gout and kidney stones. Uric acid turns out to be a central player in metabolic syndromes.

As a matter of fact, that's the title of a collaborative paper that was written in 2016 by a Turkish and Japanese researcher. "Uric Acid and the Metabolic Syndrome: From Innocent Bystander to a Central Player," focusing our attention on how uric acid doesn't just happen to be elevated in diabetes, hypertension, and obesity. It's playing a mechanistic, causal role, and that's empowering as can be.

If we know that, we embrace it and we understand that we now have an incredibly powerful new tool in our toolbox to rein in this metabolic mayhem that is globally pervasive.

Shiv Gaglani: It is fascinating. You've preempted a lot of the questions I had about how you went from neurology to then nutrition, and then the books. Two things that immediately stand out, I would like to double click on. One is the concept of lifelong learning. Remind me, when did you graduate from medical school? Which year?

Dr. David Perlmutter: 1981.

Shiv Gaglani: So, 40 years later, you're still reading hundreds of peer-reviewed papers as you work to create new books and educate yourself first for your patient care, but then educate the world about these issues. I'm curious on advice that you have for our audience about what drives this. Is it just curiosity? How do you maintain that attitude of lifelong learning? Because what people taught me in med school was smoking is good for asthma.

There are a lot of things that constantly are being revised, and it's hard -- especially with COVID now -- to know what's true. Does hydroxychloroquine work or not? There are all these competing papers that come out. This is the process of medicine. It's an art sometimes, not a science. Any advice on lifelong learning, and then I'll ask the second question after that.

Dr. David Perlmutter: Yeah, I think lifelong learning is good for you. It's good for your brain. I don't do it because of that. I'm happy that I do it because I know it's therapeutic for me. I do it out of curiosity. There are still a lot of unanswered questions and more and more every day, which is a good thing.

We don't know it all. I mean when I was in medical school, the notion that our brains could repopulate with new neurons was blasphemous. If we would have mentioned that, they would have thrown us out. And the notion that our lifestyle choices affect the expression of our DNA? Epigenetically? Absolutely ridiculous. They would never have considered that. 

My point is, I think it's important to look at long-held tenants and recognize that nothing is sacrosanct. I'm not saying to be iconoclastic day in and day out. But there's nothing there that can't be overturned. I mean, 30 years ago we were all saying, "everybody's got to be on a low-fat diet. If you eat any kind of fat, even olive oil, that's a terrible thing. You're going to have a bad health outcome." How far we have come. We've turned that around 180 degrees, that's for sure. 

It's the discoveries that I am loving. It's the ability to change your messaging that I'm very comfortable with, but I think audiences need to be comfortable with it as well. Recognizing that is what you and I are talking about right now. We may get together in another couple of years on a podcast and there may be a different set of dogma at that point that we have to accept. It's the appreciation that science is dynamic, and that's what you want. My gosh, if we accept the status quo, we won't have any progress. Ronald Reagan famously said that "status quo is a Latin term that means 'the mess we're in.'" Truly, we're not going to move the ball down the field if we don't challenge our long-held beliefs and do our due diligence, look at the science, and make sure it's good science. And then, move forward with what we recommend to people, and what our messaging is about.

For me, it's mostly about curiosity. What can I say? On a podcast, somebody asked a question. They said they get pain in their feet when they eat tomatoes. “You're a neurologist, Dr. Perlmutter, what's the answer?” That's a tough one, and I said, ‘maybe there's a nightshade sensitivity -- tomatoes, potatoes, eggplant, green peppers.’ 

Then, I realized I don't know that much about solanaceae, that group of vegetables. I needed to learn more about the specifics of the chemicals in that family of vegetables that are there to protect themselves against being eaten by insects. 

What I learned was quite interesting. There are genetic polymorphism that people have that predisposes them to having bad reactions when they eat -- I hate to say the deadly nightshades -- but the nightshade vegetables. It's just so exciting to think about. That's checked off now. We understand that a little bit more. I think it's mostly curiosity, to answer your question.

Shiv Gaglani: I love that. And it's important because if we're to provide the best care for our patients, we can't be operating with information that's 20, 30, or 40 years old and not be open to what they're telling us. Many times, they have their own knowledge about their own conditions and what works, or what doesn't.

Dr. David Perlmutter: No doubt about it. I learn more from patients than they learn from me. People bring you articles and something they found even on the internet. You might not read it right then, but you take it home and maybe just before you go to sleep, you glance at a paper or something that somebody gave you. Maybe you think it's hogwash, but it might just be the initial ping when a week later you get another one that sort of ties in, then you go through the garbage where you threw the first one and you say maybe there's something here; maybe there isn't.

Louis Pasteur famously said that chance favors the prepared mind. You've got to keep doing your work. Then, when you're going to have something serendipitous happen -- in this case, perhaps in your treatment of a patient -- it's because you're prepared for it. You've done the groundwork.

Shiv Gaglani: Totally. 100 percent. I love that quote, too. There's a great book by an author and a professor named William Irvine, who's famous for stoicism. He wrote this book called, Aha! about moments of insight that have shaped our world, ranging from moral and religious to scientific. There are a lot of examples of medical insights and people who were famously rebuffed for insights that they had. One example are the pathologists who I think were in Australia who discovered that H. pylori contributes to stomach ulcers and the gastroenterological...

Dr. David Perlmutter: Barry Marshall.

Shiv Gaglani: Marshall. And the famous empirical experiment he did on himself, when he drank H. pylori.

Dr. David Perlmutter: Right, he chugged some H. pylori. That's pretty well dedicated to following your beliefs, isn't it?

Shiv Gaglani: Yeah, exactly. He wound up getting the Nobel Prize for this discovery whereas other people like Semmelweis went down as quacks for insights they had. The science didn't catch up to their insights. How do you view this? Because you've put your name out there. You've done a lot of really interesting talks, studies, and books.

Some of the things are controversial, and in this day and age with the infodemic, how do you straddle both what your patients are telling you, and what you're learning with kind of the dogma of the existing medical community? Some of them are not very kind as far as how they view these beliefs -- like Alzheimer's is basically Type 3 diabetes in terms of the etiology. Obviously, that is very reductionist. But how do you balance that and where do you draw your strength in terms of being able to put those views off?

Dr. David Perlmutter: It's tough. As any human would do, I look at the source and what else that source has provided. At the end of the day, it's the quality of the science. An opinion paper is one thing -- maybe you have a lot of great information -- but I want to see a study. I want to see a large study that's well-controlled that demonstrates significant meaning and significant outcome, for example, from an intervention.

I'd like to see not hubris as much as people accepting that their study is less than perfect. The idea is that more work needs to be done, so it's a little bit of humility as opposed to hubris.

Shiv Gaglani: Yeah, that makes a lot of sense. The other thing you mentioned, as you were going through this, was that we have this information. We're solid on the actual information. There has been a large enough effect size for nutrition or exercise.

Hippocrates even said famously, “Let thy food be thy medicine, let they medicine be thy food.” Behavior change is an issue. We've had several people on the podcast who've talked about this including BJ Fogg, who's the Stanford behavioral scientist who wrote the book, Tiny Habits on how to change behavior.

What are some of the behaviors you've most effectively changed in yourself, or your patients? And what advice would you give to our audience about taking that next step from just having education and recommendations into actually helping their patients change their behavior?

Dr. David Perlmutter: Shiv, it gets back to behavior being the decisions that we make in any particular circumstance. That ultimately becomes our behavior. What do you do each day? What is your behavior like? It's based on decision-making.

What I'd like to do is recognize that bad decisions beget bad decisions. Because you're compromising the decision-making apparatus, making bad decisions increases inflammation. As I talked about earlier, it takes the adult out of the room, and you're locked into a very primitive self-serving, impulsive decision-maker called the amygdala -- basically, the five-year-old in the room -- and you can't get out of your own way.

What we like to offer are on-ramps to better decision making. In other words, get that individual to start a little bit of exercise, or maybe it's going to bed on time, or it's a little bit of nature exposure, or meditation, or a little bit of a dietary change…whatever we can do just to start to tip the scales of decision making in a more positive way. It works and it allows people to regain control.

There are many influences in our modern world that are keeping people physiologically away from their prefrontal cortex. The media does it. The time spent in front of a screen each day when other things could be happening in your life is locking people into impulsivity, especially things like pop-up ads and things that increase stress. You don't measure up for one reason or another, amplifying cortisol and gut permeability, and as such turning on inflammation, which keeps you from accessing your prefrontal cortex. The lack of physical activity and engagement with other people…all of these things tend to fan the flames quite figuratively and literally. When I say "inflammation," I say fan the flames. It comes from the word, “inflammare” which is Latin for fire.

Inflammation means quite literally that you're turning on the fire in your brain and burning up that pathway to be better able to make good decisions. It's the small steps that are unique to that individual patient. What does he or she need? You're not going to tell every patient, "All right, do me one favor. Tomorrow, I want you to go out and run five miles." It might be, "I want you to walk to the mailbox at the end of the street and come back." Or it might be, "I want you to buy a potted plant, and put it in your living room."

That's the art of medicine. To feel out what might work best and easiest and create something the patient can do, not focus on what they can't do. Once you get somebody to do something that they can do -- even as simple as putting a plant in their living room -- they've done something. They finally have gained a degree of agency and that is hugely empowering because then they realize that they, to some degree, are running the show. 

Shiv Gaglani: I love that. This is one reason I'm a big supporter of not just tiny habits and giving them some agency, but the fact that they believe in something. An average patient may not be able to read a PubMed paper and get to the etiological root of how something works. But if they believe in some sort of advice, it gets them on an on-ramp to this stacked habit formation. If they're sleeping better, they're having more energy to exercise, which then gives them endorphin spikes throughout the day.

It's all kind of, as you said, a positive feedback loop. Going from the macro -- which is the stuff you've written about and published about in these journal articles -- to the individual, what are some of the lifestyle changes that you found to be most useful? Even down to the macro level, I'm interested in how many macros of carbs you eat, as an example?

Dr. David Perlmutter: It's hard to say. My lifestyle choices, like everyone else’s, continue to change as we learn more and more about whatever it may be. Time-restricted eating is kind of a new idea. Things kind of come and go, and people have challenged that at least in terms of weight loss. Because I'm not so young anymore, I'm 67, it's important for me not to diverge from the choices that I think are important. For me, I make sure that I get enough sleep. I could stay up pretty late reading if I didn't make myself turn the light off and go to sleep. That's very important. 

Diet-wise, I generally don't eat until twelve or one, because I just don't. I'm quite aware of an eating window and why that's valuable. The work of Dr. Satchin Panda, of course. But I'm exercising in the morning and doing other things. I exercise every single morning. I have to keep my body in shape because I really depend on it. Who doesn't, right? And that consists of a good 45 minutes of stretching and yoga, bout 150 crunches, 50 pushups, curls with a tension band, and at least 30 minutes on the elliptical machine or 45 minutes to an hour of running. That's every day.

Of course, if you travel that might not happen, but every day that I possibly can, I do that. Then, my afternoons are doing things that are involved with the work that I do, as well as interviews. I do probably three a day, at least. Then, I'm always writing. I'm writing articles. Right now, I'm between books. But I know what my next book will be.

I generally have a book on the burner somewhere that I'm working on, at least mentally. There's always a book in the future.

Shiv Gaglani: Can you preview? I don't know if you can preview what the topic is.

Dr. David Perlmutter: Yeah. I'm thinking of writing a book called Mismatch, that focuses on the mismatch that we are experiencing between evolution and environment. At the core of our panorama of illnesses today is that we are living a discordant life. We're influencing our bodies in such a way that it doesn't line up with our physiology that is dictated by our long-evolved genome. 

That's really the underpinning of Drop Acid. We, as humans, have evolved to have a very high uric acid level as a survival mechanism. Having the high uric acid -- because we lost the genes that would have coded for uricase, an enzyme that breaks down the uric acid -- we have a higher uric acid level, and therefore, we survive when there's no food for long periods. We make a little bit more fat because we have a higher uric acid level than other mammals.

Now, of course, we're seeing the consequences of having a high uric acid level. That's the mismatch. Our physiology gives us this beautiful gift and yet, we send the signals to our physiology that winter's coming, we need to make and store fat by eating a lot of fructose as an example. That's the mismatch I'm talking about.

The mismatch has to do with our lack of physical activity, lack of exposure to sunlight, the amount of stress in our lives, etc. There are so many things about our modern world. It's sort of the underpinning of the Paleo mentality, that if we can emulate the experiences and the environment of our Paleolithic ancestors, we'd be more in line with our genome.

Interestingly, for me, this is going to be a full circle because my first paper on this topic was published half a century ago in 1971, probably before you were born, in the Miami Herald. I concluded that missive by asking the question: “What about us who are living today with this outdated machinery?” Meaning that our bodies, and our physiology as dictated by our genome, is really more appropriate for another time…a time when we were stressed by food scarcity and other types of stress. We were less comfortable. It's this mismatch that as I mentioned is at the cornerstone of our extensive list of chronic maladies that we're suffering from.

Shiv Gaglani: That's fascinating. I can't wait to read that because there are so many good examples of that. Science has done a tremendous job of helping us overcome natural selection. 

My last question for you is, go back to 1968 when you were starting medical school around that era. What advice would you give to a young Dr. Perlmutter about approaching his career in healthcare? Is that the same advice you'd give a current student, or would it diverge? Any advice you could give our audience would be great.

Dr. David Perlmutter:  I would say be more open-minded. Understand that medical schools are very curriculum-driven and that there is significant industry influence on that curriculum. It's unfortunate, but it's reality. I'd say be much more open-minded, question everything you're being told. Beyond that, do your best to be as open-minded as you can about the incredible influence of lifestyle choices that people make in terms of their health.

In America and western countries in general, we practice reactive medicine. People come in with a problem that has already developed and then we do our best to help them. I think it would be valuable to spend some time focusing on learning about proactive medicine -- also known as preventive medicine -- keeping people healthy in the first place and wondering how did they get to this place? When the next patient that comes in, we're going to think about that and put that into play.

You're not heroic when you're being involved in preventive medicine. You're not cathing a coronary artery at three o'clock in the morning, or whatever it may be, and being the hero. But there's a lot to be said about talking to people about their exercise program and their diets long before that coronary artery became occluded. I think those are the recommendations I'd make.

Shiv Gaglani: Great advice on being open-minded, staying curious, and being a lifelong learner and again, sharpening the ax as we like to say. Dr. Perlmutter, thank you so much for not only taking the time to be with us today, but more importantly, for the work that you're doing to advocate for all these lifestyle changes not only with healthcare professionals, but with the general public.

Dr. David Perlmutter: Shiv, I want to thank you for having me today. Great questions, and I'm glad we got to explore these areas, because I think they're really important. Thank you again.

Shiv Gaglani: Likewise. And with that, I'm Shiv Gaglani. Thank you to our audience for checking out today's show and remember to do your part to flatten the curve and Raise the Line. We're all in this together. Take care.