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Episode 585
The Doctor's Farmacy

How To Upgrade Your Metabolism with Dr. William Li

Open the Podcasts app and search for The Doctor’s Farmacy. If you’re viewing this site on your phone, you can just tap on the

Tap the subscribe button and new shows will be added to your library.

If you’re using a different device, our show is available on the following platforms.

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Many people think of metabolism as one specific system in the body, when in fact it’s the sum of many different processes that are serving other vital roles for us as well. 

Our bodies are not closed systems, so our environment, social networks, diet, hormones, microbiome, genetics, and more, all influence how well our metabolism works, or how well we can extract energy from our food.

I’m so happy to sit down with my good friend Dr. William Li to talk about what metabolism really means, why the old way of thinking about metabolism hasn’t helped us, and how to make positive impacts on our metabolism at any age. 

We dive into our conversation with a history of the “calories-in, calories-out” model of metabolism and why our thinking about weight gain and weight loss has been completely wrong. 

Dr. Li shares some of the most revealing studies on metabolism and what they tell us about the metabolic phases we will all go through in life. Humans are hardwired to go through the same stages of cellular metabolism as we age, despite the fact that we all have a friend who seems to eat whatever they want without gaining weight. 

We also get into the different types of fat and the purpose they serve for our bodies. When we activate brown fat, for example, we speed up our metabolic processes, and there are certain bioactives in foods that can nudge this pathway in the right direction.

We also talk about the bacteria Akkermansia muciniphila, how hormetic stressors work to support our health, and so much more. 

This episode is brought to you by Rupa Health, Cozy Earth, and InsideTracker.

Rupa Health is a place where Functional Medicine practitioners can access more than 2,000 specialty lab tests from over 20 labs like DUTCH, Vibrant America, Genova, and Great Plains. You can check out a free, live demo with a Q&A or create an account at RupaHealth.com.

Cozy Earth makes the most comfortable, temperature-regulating, and non-toxic sheets on the market. Right now, get 40% off your Cozy Earth sheets. Just head over to cozyearth.com and use code MARK40.

InsideTracker is a personalized health and wellness platform like no other. Right now they’re offering my community 20% off at insidetracker.com/drhyman.

I hope you enjoyed this conversation as much as I did. Wishing you health and happiness,
Mark Hyman, MD
Mark Hyman, MD

Here are more details from our interview (audio version / Apple Subscriber version):

  1. Shifting away from the idea that eating less and exercising more is the key to weight loss
    (4:51)
  2. How calories affect metabolism
    (13:14)
  3. Research measuring the four phases of metabolism as we age
    (16:07)
  4. What is metabolism?
    (24:03)
  5. Common myths about metabolism
    (28:35)
  6. Supporting the gut microbiome to raise metabolism and promote health
    (36:18)
  7. Foods that mimic caloric restriction
    (40:27)
  8. Our body’s ability to reverse disease
    (52:59)
  9. Reducing stress in a doomscrolling society
    (54:07)
  10. How to restore health to your metabolism
    (56:03)

Guest

 
Mark Hyman, MD

Mark Hyman, MD is the Founder and Director of The UltraWellness Center, the Head of Strategy and Innovation of Cleveland Clinic's Center for Functional Medicine, and a 13-time New York Times Bestselling author.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

 
Dr. William Li

Dr. William Li is a world-renowned physician, scientist, speaker, and author of Eat to Beat Disease – The New Science of How Your Body Can Heal Itself. He is best known for leading the Angiogenesis Foundation. His groundbreaking work has impacted more than 70 diseases, including cancer, diabetes, blindness, heart disease, and obesity. 

His TED Talk, “Can We Eat to Starve Cancer?” has garnered more than 11 million views, and he has appeared on The Dr. Oz Show, Martha Stewart Live, CNN, MSNBC, NPR, Voice of America, and has presented at the Vatican’s Unite to Cure conference. An author of over 100 scientific publications in leading journals such as Science, the New England Journal of Medicine, The Lancet, and more, Dr. Li has served on the faculties of Harvard, Tufts, and Dartmouth Medical School.

Mentioned in this episode

Perspective: Obesity-an unexplained epidemic

Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models

Daily energy expenditure through the human life course

Get a copy of Dr. Li’s book, Eat to Beat Disease: The New Science of How Your Body Can Heal Itself, here and check out his Masterclass with Dr. William Li here.

Transcript Note: Please forgive any typos or errors in the following transcript. It was generated by a third party and has not been subsequently reviewed by our team.

Introduction:

Coming up on this episode of The Doctor’s Farmacy.

William Li:

When we actually feed ourselves good quality calories and we actually do the things that we’re supposed to do, which is stay physically active, and get good quality sleep, and actually lower your stress, all of these things converge to really help our metabolism actually rightsize itself.

Dr. Mark Hyman:

Welcome to The Doctor’s Farmacy. I’m Dr. Mark Hyman and that’s Farmacy with an F, a place for conversations that matter. If you care about your metabolism and wonder what’s wrong with it, why it doesn’t work the way you want it to work, and how to speed it up, and how our thinking about weight gain and weight loss is completely wrong, then this is the podcast you want to be listening to because it’s with one of my good friends, an extraordinary scientist, one of the leaders in thinking about food as medicine. My hero, Dr. William Li.

He is a world renowned physician. He is a scientist, speaker, and author of one of the best books on Food as Medicine called Eat to Beat Disease, way better than my books, I’m just saying, The New Science of How Your Body Can Heal Itself is best known for leading the angiogenesis foundation. His groundbreaking work has impacted more than 70 diseases, including cancer, diabetes, blindness, heart disease, obesity. His TED Talk, Can We Eat to Starve Cancer has been seen 11 million times. He’s appeared on The Dr. Oz Show, Martha Stewart, CNN, MSNCBC, NPR, Voice of America. He’s presented at the Vatican’s Unite to Cure Conference. He invited me to that conference. Unfortunately, COVID squashed that conference. I didn’t get to go, but maybe another time when it’s open. He’s an author of over a hundred scientific publications in leading journals like Science, New England Journal of Medicine, Lancet. He’s served on the faculty of Harvard, Tufts and Dartmouth Medical School. Welcome, William.

William Li:

Thank you very much, Mark. Always a pleasure to talk together.

Dr. Mark Hyman:

We were just chit chatting a little bit earlier about the shift in science around our understanding of metabolism and this hypothesis that we’ve all been believing for the last decades and decades, which is this. If we eat less and exercise more, we’re going to lose weight. In fact, that’s what all of our dietary recommendations are about. That’s what you’ll hear from your doctor, from your nutritionist, from all the professional societies like the Academy of Nutrition and Dietetics, AMA, the ADA, American Diabetic Association, pretty much you’ll also hear it from obviously all the food industry experts, because if it’s all about calories, then 100 calories of soda are the same as 100 calories of almond. It’s just about the calories and if you eat less and exercise more, you’re going to lose weight. We are just chit-chatting about the shift in the paradigm.

This morning, I was reading this article that our friend Dariush Mozaffarian wrote called Obesity-an unexplained epidemic. Obviously, you can’t read it on Zoom, but we’re going to put it in the show notes. It’s available and free. It really challenged this notion that it’s all about calories, because in the article, he shares data. This is hard data from large government surveys that in fact, since 2000, last 22 years, we have eaten less and we’ve exercised more and yet, we’re getting more and more and more overweight and more and more diabetic. How do you sync that up if it’s not all about calories, it’s not all about energy balance, I’m not all about eating less and exercise more? What do you think about this, William? How do you come to shift your thinking around the idea about calories?

William Li:

I think you just set that up perfectly, Mark, which is that we’ve had this notion for decades. In fact, I’ll actually throw the stone even further back in time back to like the 15th century, 16th century, when the first people to even come up with the measurement of metabolism, the Sanctorio Santori, this guy, he created a chair that he could sit in with a dinner table in front of him and it was suspended by a chain. He could weigh what he weighed and how much food he ate, and he actually collected his urine and his feces. He would compare to what he was actually eating. There were these great wooden engravings going back to medieval times with this calories in and poop and excrement out.

It’s not false. It’s a good, basic principle, but where we are now is we are light years ahead in our refined understanding of not just calories, but how the body processes what you put into it. It’s kind of like fuel. You got a nice car. If you’re actually putting good quality engine oil, and a good quality calories in the case of your body, your car is going to drive a little bit longer. It’s going to perform better. It’s going to be happier and you’re going to be happier with it for a longer period of time. If you take really crappy engine oil or look at your fuel tank and you put the cheapest quality fuel into the best car that you want to actually keep for a long time, it’ll drive for a little while, but the toll will be taken. I think that’s really one of the things that this research-

Dr. Mark Hyman:

Wait, William, that reminds me of a story when I was in residency, I lent one of my fellow residents my car and it was a diesel car.

William Li:

Oh, no.

Dr. Mark Hyman:

And he put gasoline in it, the worst thing. It’s kind of what we’re doing to ourselves, really.

William Li:

Yeah. Well, listen, I mean, just like the friend who you lent the car to, you have to be informed about what you’re putting inside your chassis, your fuel tank. I think that’s really the biggest misconception that it’s simply a number, like a calculator, calories in, calories out. If you exercise, if you eat less, you’re going to be all set. As a matter of fact, the quality of the calories makes a huge amount of difference. You could have the same number of calories in a can of soda as you could actually have in a plate of fruit. They would obviously be radically different because of the effect of the micronutrients on those aspects of your body.

Dr. Mark Hyman:

I’ll tell a funny story. I was on The Today Show years ago. It was, God, I don’t even know, maybe, I don’t even know, 2006 or 7. I was on it about one of my books. After I was chatting with the producer, I said, “I have a great idea for a segment.” She’s like, “What is it?” I said, “Well, why don’t we do a segment on 100-calorie, because at the time, 100-calorie snack packs were like 100-calorie Oreos, 100-calorie M&M’s, 100-calorie whatever.” I’m like, “Let’s do a segment on like 100-calorie and talk about 100 calories of blueberries versus 100 calories of Oreo cookies.” I had a whole table full of this stuff.

Somehow, it slipped under the radar and they were like, “Yes.” I got on and all of a sudden, the host and they get kind of briefed a little bit beforehand, realized what was happening and the advertising for all the television were either drugs or junk food. You look at television advertising things and it was threatening all of their advertising partners. And so, she tried to redirect the whole thing, because I was like, “Listen, here’s how 100 calories of blueberries affect your body, and here’s how 100 calories of soda affect your body.” Then, I got kind of excommunicated from The Today Show for years and years.

William Li:

Well, but you know, I think that these points that we’re making are so fundamental. I would say anybody watching or listening to this is going to recognize that it’s almost like a truth that if you just count your calories and you go to the gym, you’re going to actually lose weight. You’re going to be fine and it’s clearly not the case. What’s actually happening, I mean, if you take a look at what our body does to maintain healthy function, let’s talk about function before we get into the depth of metabolism. Look, we’ve got our circulation fuels, our muscle brings blood and oxygen to our muscles. Our immune system controls inflammation and allows us to actually combat all the attackers that are coming to us from the outside and also the inside of our body. We’re exposed to environmental pressures like ultraviolet, radiation and radon from our feet.

It’s amazing that we’re actually not sick more often, but fortunately, all of those myriad of environmental influences are defended against by our body. And so, when we feed ourselves, it’s no different than walking into a cloud of something. If you walk into a cloud of synthetic chemical junk and you’re breathing it in, you know that you’re going to come out of it feeling sick. I mean, that’s the 9/11 effect. This gigantic pile of stuff put up dust everywhere and people got sick. There’s no surprise. I think that what we’re now realizing, I think this is a wake up call that the public is actually having and the scientific community is digging into it now is that when we actually feed ourselves good quality calories, and we actually do the things that we’re supposed to do, which is stay physically active. You don’t need to work out, you need to be active, and get good quality sleep and actually lower your stress, all of these things converge to really help our metabolism actually rightsize itself.

Dr. Mark Hyman:

Yeah, and so true. Your book Eat to Beat Disease was so important because it really took the macro framework of what Hippocrates said 5,000 years ago, which is like, could be that medicine and medicine by that food and made it very granular, very scientific and very specific and showed exactly how different compounds in different foods, and I’m talking about actual food, not processed food, affect your body and regulate every single biological process. And so, that’s such an important idea that food isn’t just calories, it’s actually information that it’s medicine that this instructions are code that regulates everything that goes on is so important. Now, I can imagine that there might be some physicists out there listening to this and saying, “Dr. Hyman, Dr. Li, you guys are smart and all that, but really, you’re not physicists. You don’t get this basic thing called the first law of thermodynamics.”

Well, guess what? We had to take physics going into medical school. I know where that lies. That law, if you read it really carefully says, that energy is conserved in a system, in a closed system, so yes, if you take 1,000 calories of soda and 1,000 calories of broccoli and you put them in a lab, they will actually release exactly the same amount of energy. All a calorie is the amount of energy required to raise the temperature of one liter of water one degree centigrade, that’s it.

But another example, if you take feathers and lead and you drop them in a vacuum, they drop at exactly the same rate because there’s no air. If you drop them off a bridge, the lead goes boom and the feather kind of float down in the air. Well, it’s the same thing when you eat. Your body has something called metabolism. It has the microbiome, it has an immune system, it has hormones, it has neurotransmitters, it has peptides and messenger molecules, all of which are being influenced, not just by the caloric intake of what you’re eating, but by the informational quality of what you’re eating. And so, it has profoundly different effects on everything and it’s not the same. Yes, the first law of dynamics is true. I’m not discussing that, but it doesn’t hold in a system called the body.

William Li:

Because our body is actually made of different systems that are interconnected and it’s not just a system in a snapshot in time, but over a period of time. It’s not a Xerox, it’s not like a photocopy. It actually, our body is shifting over time as we age. There all these little gears and parts are all moving and responding to that information. Here’s the thing that I… Listen, I’m a internal medicine doc like you. I’m a vascular biologist and I’ve been involved with biotech development. For me, I’ve always been curious on the mechanisms. What do we understand about a molecular or cellular process that drives a disease and if we understand that, could we apply the science to come up with a solution? That’s really how immunotherapy and antiangiogenic therapy and all these growth factor therapies, this is modern medicine at its best from a technology perspective.

However, what really drew me into the nutrition world was I realized that when we’re diving after a disease, including obesity by the way, we’re trying to figure out what causes the hurricane while we’re in the eye of the storm. Everything is blowing around us. The roofs are coming off, ducking for cover. And so, one of the things that I think is so fascinating to me as a scientist and as a doctor, is really going back to take a look at well, what happens before you’re sick? What’s the basic function of the body before we’re trashed at any age?

This is where a profound study was published in 2021 in the Journal of Science, one of the most credible scientific journals by a guy named Herman Pontzer, who’s a professor at Duke University. He worked with colleagues from 19 other countries to look at 6,000 people and asked what was their metabolism like. And so, the 1Zs and 2Zs and the 3Zs studies that have been done on metabolism or people that are doing sports strengths or athletes doing research studies, that’s one thing. But what they did is they took a look at, it’s amazing, they took a look at people that were just a few days old to 95 years old. They applied the exact same measurement system, which uses a form of water that has an atom that you can actually measure in a room. Talk about a closed system. You put these people into closed system and you give them this cocktail to drink and it’s just water.

Dr. Mark Hyman:

It’s like radioactive water kind of, but not really.

William Li:

Yeah, exactly. People then become Spider-Man, all right. But what wound up happening is that they could actually measure from their breath ad their urine how their body was using metabolism and what they found was, of course, everybody’s metabolism was all over the place. Information, so put information in. They’re eating and drinking, information out. They’re measuring, it looks like a mess. Except one of the things that they did is they corrected, they developed back to the physicists, they used mathematics to kind of correct for age, size, sex, and this is really kind of the mic drop here, they corrected for body fat. What they realized is that everyone’s going to have a different level of body fat from the time they’re a baby to their time they’re in their 90s across the age span.

When they did that, this chaotic data set suddenly clarified itself into four phases of human metabolism as we age from a few days old until we’re in our 90s. That really changed my mind when I saw that data to go, this is like a eureka moment, that humans all are hardwired and it makes total sense to go through the same stages of cellular metabolism as we age. And so, there’s four phases. Zero to one is one phase. When you’re born, we’re corrected for body size. We have the same pace of metabolism as our moms did. That makes sense. We were synced with our mom’s metabolism corrected for size, but from zero to one, our metabolism source to about 50% of higher than what we’re going to have when we’re an adult, and that’s why neonatal nutrition, what we feed our babies in the first year of life is so profound. All those cells are taking in those calories, the nutrients, breastfeeding, everything counts in the first year of life. From the get go, what were the fuel that we’re giving our bodies actually can make a huge difference going downstream.

From one years old, down to 20, our metabolism actually starts to go down to adult levels. And so, when you’re a teenager and you’re seeing teens eat two or three dinners and their growth just spring up a tree, right? What do we always say? Like, “Oh man, our kids are sprouting like trees. Their metabolism’s going crazy.” Actually, the metabolisms is going down, heading down towards adult levels. Surprise, right? Then, from 20 to 60, that’s during college age, your first job, your marriage, if you get divorced, your menopause, all those kinds of things, where people-

Dr. Mark Hyman:

What does divorce even do to your metabolism?

William Li:

Well, it’s stress. Menopause, all those kinds of things. Actually, it’s a straight line of how our bodies program and only at 60, at 60 years old, in our sixth decade, our metabolism start to decline very, very slowly, so that by the time we’re 90, our metabolism at 90 years old is 75% what it was when we were 60. As adults-

Dr. Mark Hyman:

But that’s not inevitable, right? I mean, that can be modified?

William Li:

That’s a key thing. You can modify it up or you can modify it down.

Dr. Mark Hyman:

Because I noticed, my metabolism is faster now at almost 63 than it was when I was 40. I actually have to work to keep the weight on because I’ve sped up my metabolism by knowing what to do to activate the right pathways, to do what I wanted to do.

William Li:

Exactly. And so, this is the perfect segue into thinking about if there’s a set pattern that humans are programmed to be able to have over the course of the lifetime, in terms of this pattern that we call metabolism, and this is again, corrected for age, sex, size, and body fat. Now, let’s start to look at what good things you can do to raise your metabolism, so what are the things, your microbiome, your epigenetics, your circulation, your inflammation. There’s all kinds of things you could do to support and elevate to get to that next level of metabolism. But at the same token, there’s a lot of things, put that wrong fuel into the engine and now you squash the human metabolism as well.

This is actually a eureka, because now, we’ve taken it way far away from calories in, calorie out. What we’re saying is that the quality matters, the systems and how we live our lifestyle matters. And so, for someone like you, Mark, I mean, and look, you and I have known each other pretty well, you’re somebody who practices what you preach and all of these things that you do, choosing the right foods, getting the right exercise, lowering your stress, managing your inflammation, getting the right sleep, all of these things actually help to elevate and get your metabolism above what the average human should have.

Dr. Mark Hyman:

Amazing. All right. Everybody talks about metabolism, but what the heck is metabolism? We have a slow metabolism, fast metabolism. What does metabolism mean? What do you even mean when you refer to metabolism?

William Li:

Well, I think we have to take a step back to essentially say that metabolism is really the process that our cells use to extract energy from food if we’re feeding ourselves and within our body to be able to power up and fuel all of the functions from the molecular, to the cellular, to the organ, to the organismic level, that’s basically what metabolism actually is. We don’t think about it that way, but I think science is telling us that there’s all these layers to peel back, to understand how actually engine runs.

If anybody who’s actually sat in a plane, you get your boarding pass, you get onto the plane, you buckle your seatbelt, you settle back for the flight. It’s kind of like getting into a plane is kind of like trying to understand metabolism. It seems kind of easy, you can settle down into the seat and just enjoy the ride. But in fact, there’s a lot going on from the cockpit, to the engines, to the fuel tanks, to the weight of the passengers and the weight of the luggage, to the delays, the air traffic control. And so, that analogy really tells us that somebody needs to be in charge of understanding this. I think that’s where folks like you and I, Mark, are really trying to play our role in digging into what the science is actually showing and connecting dots with what everybody already understands. Whenever there’s a misconception, we got to try to clear that up.

Dr. Mark Hyman:

I would just sort of add to that. I mean, some will define metabolism as a sum total of all chemical reactions going on your body. It is a whole field of metabolomics, which can now measure at least thousands and thousands of things going on in your body at the same time. But when I think of it as a doctor, I’m thinking about how do like optimize my patient’s health and how do I work with their metabolism to make it work better so that they can get the energy they need to live life, so they can optimize all their biological functions, how they can use food as medicine. When I’ve come to realize, there’s so many things that influence it that are far beyond calories and energy.

One, you talked about the quality of the calories. There’s the macronutrients, which is protein, fat, and carbohydrate, and what’s the quality of the protein. If you eat steak from a grass-fed or let’s say a wild kangaroo versus a feedlot cow, very different effects on your information and metabolism. If you eat a carbohydrate from refined high-fructose corn syrup or from asparagus, very different. If you eat a fat from Crisco or omega-3 fats, very different. Calorie for calorie. Everybody understands that. It doesn’t take rocket science. There’s the macronutrients.

There’s a fiber also, which is very complicated in terms of how it affects the microbiome. There’s the vitamins and minerals. There’s all these phytochemicals that you write about in your book Eat to Beat Disease. These phytochemicals turn out have profound effects on all kinds of regulatory pathways that have to do with how we burn calories, how our mitochondria work, how our immune systems work, what happens for microbiome. Then, of course, there’s all the other things we have to deal with like all the toxins that are around that affect our metabolism. They’re called obesogens that literally interfere with our metabolism.

Actually, I was in the White House, you’d be interested. I went to Washington, I was in the White House this week and was talking to the head of the White House Conference on Hunger, Food, Nutrition. She said, “What do you think about this whole thing about toxins and metabolism?” I’m like, “Yeah, it’s a thing. I wrote an article about it 15 years ago and it’s real and I see it in my patients.” There’s so many different factors that influence the system, because our body’s not a closed system. Of course, there’s effects of stress and our beliefs and epigenetics. And so, all these, it sounds super complex and there’s hormonal effects. How do our hormones affect it? How do our sex hormones affect our insulin, our cortisol? All these things that happen. In a sense, it’s kind of complicated, but when it comes down to it, the to-do’s are actually pretty straightforward on the what to-do’s. Let’s-

William Li:

Before we dive into the do’s, I also want to maybe just to bring it home to people who are listening that are not really into the learning about all the different aspects of the science and keeping up with all the very important things you just said. Here’s what it boils down to. Most people realize that their body’s metabolism is connected to their weight. I mean, even a kid in grade school learns that pretty early on. Here’s one of the things that I think, for metabolism, it’s so complicated what we’re learning, maybe it’s simpler to help people understand what we’re learning is not correct. What are the myths of metabolism?

One of the myths we just talked about is the fact that a calorie is a calorie. Just count your calories and exercise, and you’re going to be all set. That’s not true, obviously, and the quality obviously matters. The second thing that’s really interesting is that, how many people have you heard say, “My sister or my sibling was really lucky because he or she was born with a fast metabolism and look how skinny he or she is.” Then, of course, the other line is that, “Well, look. I wasn’t so lucky. I was born with a bad metabolism and that’s why I have so much struggle with my weight.” I can’t tell you the number of patients I’ve actually heard from that. Actually, honestly, when I was in medical school, I drank that Kool-Aid too.

Dr. Mark Hyman:

Yeah, for sure.

William Li:

Because that’s the stuff that we learn, and yet you don’t really find that in a textbook. That’s just the populous belief. Here’s what the science is actually showing. In fact, our body fat is our most important gland, endocrine organ in our body. Most people don’t realize this, but before you could stuff your face to get fat, your fat formed before you even had a face. Here’s a sperm and egg meet, you get your ball of cells, some of the first organs that form are your circulation in your nerves, they form these lakes and these little tributaries. The third cell after blood vessel, nerve, that forms in your body is adipose cell.

Dr. Mark Hyman:

Wow.

William Li:

The fat forms. In fact, your fat forms before any other organ. You got to ask yourself a question, which is what I’m doing now. I’m diving deep into this stuff really like a scientist trying to understand what’s going on. Adipose tissue communicates with your circulation, communicates with your nerves, and is actually an endocrine hormonal organ. It produces at least 15 hormones that connect to your brain, to your stomach, to your immune system. All these other things, adiponectin is one of them that certain foods can make your fat, you want to feed your fat good stuff so it makes better hormones for you. But fat, like any other tissue has to be tamed. And so, I think that’s another kind of myth to be busted is that fat, it must die. Wrong. Fat keeps us alive. It’s when it gets untamed-

Dr. Mark Hyman:

You want smart fat, not angry fat.

William Li:

That’s right.

Dr. Mark Hyman:

Because I think our friend David Ludwig talks about how the way we have eaten with these refined carbohydrates and starches has created hungry fat. Our fat cells are literally hungry and he challenges amidst that overeating causes obesity. I mean, I don’t think there’s probably a, except a handful of people who understand the science, who don’t believe that overeating causes obesity. What he says is it’s the other way around. If you start to accumulate weight, it’s the fat cells that make you hungry that cause overeating. It’s actually being obese makes you overeat, really a very different, and it also makes you exercise less and the way it affects your body. The question then is-

William Li:

It’s a domino effect.

Dr. Mark Hyman:

The question is how do we then change our diet to address this? Because the predominant theory has been about energy balance, which is what we talked about, calories in, calories out. I wrote a lot about this in my book Food Fix, because it was really a very political thing. And the Coca-Cola funded to the tune of about $20 million aspects of this energy balance idea and trying to get scientists to prove that it’s all about calories in, calories out.

David has come up with a different framework called the carbohydrate-insulin hypothesis. This paper that was published by him and other leading scientists and heads of societies was called Competing paradigms of obesity pathogenesis, means what are the different paradigms of why we gain weight, energy balance versus carbohydrate insulin models. What they say is it’s the quality of the calories has a profound effect on your hormones. What happens to those fat cells? What hormones do they produce in response of different calories? If you’re eating starch and sugar, which is the predominant foundation of our modern diet, you’re triggering all the wrong messages that literally slow your metabolism.

When you eat a bagel, you’re slowing your metabolism down, which people don’t realize when you eat fat and the right fat, you’re speeding it up. He did this crazy study, where he took overweight people. He gave a crossover study, which is kind of the best kinds of experiment you can do, where you take the same people and feed them different diets in different time periods. You’re testing sort of-

William Li:

Hypothesis.

Dr. Mark Hyman:

… has integrity. He basically gave them high carbohydrate, but healthy, like low fat diet for a period of time, measured their metabolism, their metabolic rate, how many calories they burn, how many calories they ate. Then, he gave them a high fat, good fat, but very low starch sugar carbohydrate diet. He said, “The ones who are overweight…” And so, he just said, “They, eating a high fat diet burned 400 calories more a day.” Now, if you multiply that times 7, that’s 2,800 calories in a week. To lose a pound, you need to burn an extra 3,500 calories. That’s almost a pound of weight loss a week by eating the same amount of calories.

This is not some kind of hypothetical in a lab experiment with a bunch of rats or mice. This is with actual humans eating the right food in a controlled environment, which is, these studies are very expensive, very hard to do, like $12 million, which nobody wants to pay for because who’s going to pay for that kind of study. It’s not a drug company, but there was some philanthropists who funded it and it was just groundbreaking. When you hear that, you’re like, wait a minute, we, we need to rethink all this stuff about metabolism, because our old ideas just don’t work anymore.

William Li:

Well, and I’ll tell you just jumping into there that it even gets deeper than that when you look at those micronutrients, those bioactives that are present mostly in the foods that we already know are healthy, whole plant-based foods, nuts and legumes, healthy oils. The things that you and I have written and spoken about frequently, those natural chemicals, the lycopene, the quercetin, the hydroxytyrosols, they are now surfacing as players. These same natural chemicals that are found in healthy plant-based foods, whole foods actually are players because they can help sensitize our cells to absorb energy, so they improve insulin sensitivity. They can also help us switch that bad fat, undesirable fat, hungry fat into good fat, the brown fat that actually can crank up your energy burn, which is really cool.

Also, by the way, certain bioactives can intercept stem cells, so our body’s, these fat stem cells to make more fat. Certain foods can intercept them and take these baby pre-fat cells called preadipocytes and make them stay there. It’s like a traffic cop telling that car to stay right there. We can eat foods that can actually direct a traffic of fat, which I think is really remarkable.

Dr. Mark Hyman:

That’s unbelievable. I want to go deeper on what you just said because, kind of we’re staying at a high level, but you’re getting into the granular aspects of the, you call them micronutrients, bioactives, these are phytochemicals and your book Eat to Beat Disease, you map these out how they affect different body systems from immune systems, to microbiome, to your blood vessels and all this. In terms of metabolism, what are the ahas? What are the take-homes that people listening can use to start to upgrade their diet and optimize their metabolism?

William Li:

Here is a really basic one that teaches us that mother nature is really clever, very rarely does she have one system do only one thing. Usually, systems will do multiple things. In my book Eat to Beat Disease, I talked about the microbiome actually helps you speed healing, communicates to your brain, your social hormones, helps influence your immune system. Well, the microbiome actually is a critical regulator of metabolism, helps metabolize lipids, blood floating on your bloodstream, and how your body uses glucose as well. Now, not surprisingly, and some people may have heard me talk about this, in fact, on your podcast, cancer researchers are discovering that there’s certain bacteria that when present, allow your body to respond to cancer treatments so you have a better outcome.

One of them is Akkermansia. You and I’ve talked about this before. Pomegranate juice, Concord grape juice, cranberry juice actually helps to grow more Akkermansia. It has to do with the ellagitannins, these natural chemicals that cause your gut to secrete more healthy mucus that this bacteria Akkermansia loves to grow in. Now, what’s interesting is that when… This is a big study done like with 10,000 people in China, people who actually are heavier going into overweight to obese actually have less to no Akkermansia in their gut.

Dr. Mark Hyman:

Wow.

William Li:

People who are thinner, leaner, lean body mass, just because you’re skinny doesn’t mean that you don’t have body fat, but people who have low body fat actually have more Akkermansia. Akkermansia seems to be sort of this conductor of metabolism, body fat regulation, glucose homeostasis as well.

Dr. Mark Hyman:

Immune function.

William Li:

Immune function in inflammation, cancer development. I mean, just so profound. And so, this is just one example of a single bacteria and we got 39 trillion bacteria, so we’re just at the tip of the iceberg, but this is actionable. Certain foods that contain ellagitannins like pomegranate, pomegranate juice, Concord grape, cranberry, those polyphenols that are found, those natural chemicals found, polyphenols found in those fruits actually stimulate the growth of more Akkermansia.

Dr. Mark Hyman:

But you don’t want to be eating grape juice.

William Li:

But you don’t want to be eating a lot of grape. Well, that’s the other interesting thing is that this is another interesting metabolism dig-in. If you can actually have an orange, should you have a lot of orange juice? Well, there’s fiber in oranges. There’s vitamin C. There’s a lot hesperidin there, a lot of good bioactives, but there’s also a lot of fructose in orange juice. In fact, you need two large juicy ripe oranges to make… Sorry, you need eight of them to make two glasses of oranges, a tall glass. Now, when would you sit down to eight oranges? You wouldn’t. You would eat one orange and get all that other, the healthy stuff along with the orange. And so, this is why fruit juices as a general rule are not as good a choice for your metabolism than going for the whole food. This goes back to the whole food because juicing itself, it’s a kind of processing. You filter, you’re filtering out all the good stuff too.

Dr. Mark Hyman:

That’s so good. There’s all these different foods, we write about them. I want to talk about something specific, because I’m writing this book on longevity called Young Forever. We’ve both been to this blue zones. You just came back from Greece not too long ago. So did I. There’s all these different hacks. Now, we know that calorie restriction, meaning eating a third less calories can make you live a third longer and that’s been proven in animal model after animal model, but who wants to do that? You’re going to be grumpy and irritable and not the best friend to have around, but what you’ve discovered in your research is that there’re hacks. There are food compounds that mimic caloric restriction. We call these adversity mimetics. They mimic adversity, but you get to eat them, so you’re not really having adversity.

William Li:

Can you talk about that?

Dr. Mark Hyman:

Because it’s such an interesting area of research where we’re actually using the intelligence of plants to help us regulate our biology and so many good ways extend life. I don’t know if you’ve… I read the book How to Change Your mind or see the new Netflix series by Michael Pollan. I’ve been watching that and I’m like, wow, the intelligence of these plants, think about it. You take a dose or two of psilocybin and it literally relieves depression and OCD and all these things that you could struggle with for years and years and it’s revolutionizing psychiatry from these molecules that have been embedded in implants that regulate our biology. Not all of them are psychoactive, but they’re all bioactive. That’s what you write about.

William Li:

Right? Well, I mean, I think that that’s such a good point you’re bringing up, which is in many ways, if we think about ourselves as a species living on a planet and that we’re constantly communicating with things around us and plants and animals are also communicating back to us. It’s this continuous feedback loop that’s actually going on. You think about these bioactives in whole foods, they are mother nature’s way, or plants’ way of communicating to our bodies. And so, that’s really quite profound. What’s interesting is that many of those healthy plants that we already know about, tomatoes, the brassica family.

Dr. Mark Hyman:

Broccoli.

William Li:

Broccoli, bok choy, kale, they all have these sulforaphanes and sulforaphanes activate your white adipose tissue, the bad fat, that hungry fat, and actually starts to slow them down, shrink them down and direct them, traffic direct them into a different direction to become more brown, brown fat. Actually, by the way, so big bulging fat. This is the life preserver you throw off the boat to rescue somebody. That’s the stuff you don’t want around your waistline. Well, it turns out that the healthy fat, the brown fat, the burnable fat that burns on energy is not a lump. It’s very thin and it’s woven like a seamstress between your muscles.

Dr. Mark Hyman:

Wow.

William Li:

Amazing.

Dr. Mark Hyman:

Brown fat is woven between your muscles.

William Li:

Yeah, it actually sits-

Dr. Mark Hyman:

I thought it was just between your shoulder blades in your back, but it’s everywhere.

William Li:

Oh man, this is such an interesting story. I got to tell your viewers and listeners. Way back in I think the 18th century, a biologist, a naturalist in Switzerland, Conrad Gesner was finding these rodents in the mountains of Switzerland and dissecting them. They were hibernating animals. He found this thing between their shoulder blade and he said it is neither fat nor flesh, but it got bigger in the winter because he was catching these guys while they’re hibernating.

Dr. Mark Hyman:

Oh, wow.

William Li:

What later on was discovered in the early 1900s is that actually, it’s a kind of fat, it resembled sort of a fat. Then, when they jumped forward and found it in babies, they actually found that… In these rodents, it was right between the shoulder blades. They get bigger during the winter and they would actually shrink during the summer. People are saying, “Well, how come these animals don’t starve when they’re hibernating?” It’s because that they’re building up these things and this is a heat generator. This is their space heater. It was actually fueling up their metabolism.

Babies have a tube right between the shoulder blades, and for a long time, the medical community thought this brown fat’s like an artifact from evolution. It’s like the appendix. It doesn’t have any real use. Hey look, we have sweaters. We’ve got indoor heating. We don’t need that brown fat to heat us up anymore. Turns out, this is a super fascinating story. There was a 67-year-old patient that came to a Boston hospital, Mass General Hospital and had a tumor in her chest.

Dr. Mark Hyman:

Oh, wow.

William Li:

And so, they were doing a PET scan to look at it. A PET scan for those of you who don’t know, it actually measures the metabolism of a tumor. And so, cancers will light up because they’re really active, fast dividing cells. When they scanned this patient’s chest, the tumor lit up like fireworks. When they biopsy, guess what they found? They didn’t find cancer cells. They found fat cells. When they looked at the fat, it was brown fat. They were like, “Whoa, this is crazy.” They actually called it a hibernoma. All right, there’s a whole tumor category. That’s based on Conrad Gesner’s little rodent discovery of hibernating animals. Pathologists used to call this hibernomas when they used to find them.

Dr. Mark Hyman:

Wow.

William Li:

This radiologist went back and looked at 1,000 PET scans taken from adults in Boston for different reasons, all kinds of different scans. He found that people were lighting up. That this brown fat was lighting up in different places and different times. He goes one step further. Remember, I told you these rodents are hibernating in the cold in Central Europe like around Switzerland. It’s pretty damn cold in the wintertime there. What he found when he looked at the date of the scan, when it was scanned, the scans that lit up with the brown fat were all done during the winter months in Boston. Cold temperatures light up your brown fat.

Dr. Mark Hyman:

I know that.

William Li:

Then, fast forward. We now know that we’ve got a pretty substantial amount of brown fat. When they looked at where it is, it’s not just behind our shoulder blade, it’s around our neck, it’s around our girdle. It’s up behind our chest. There’s some in our belly and cold temperatures and certain foods will light it up. That’s kind of like the cool part, the bioactives in foods will mimic these temperature and other factors to really help us burn fat.

Dr. Mark Hyman:

That’s amazing, William. I actually, just in my book research on longevity, was researching about hormetic therapies, which are stresses that don’t kill you but make you stronger and better. This whole idea of cold plunges and ice baths actually is one of those things and that’s one of the things that they discovered is about the activation of brown fat, which literally speeds up your metabolism.

William Li:

That’s right.

Dr. Mark Hyman:

But also, discovered this concept of phytohormesis. Now, you say these plants develop these things that work with us. I think that we need to frame it a little bit differently, that there’s more of this symbiotic adaptation that we’ve had to these plants. They didn’t make these chemicals for us. They made them for themselves as their own part of their defense mechanisms such as there are pests, to deal with heat, to deal with sunlight, to deal with drought, I mean, just to be stronger, but we borrowed them for our own use because we’re lazy biologically. We don’t make vitamin C because we can get it from the food we eat. We actually don’t think of these things as essential nutrients, but I think they are. They now can mimic these things that we need that are little stresses in our body. A high dose, for example, will cause potentially some toxic effect, but if you eat them in the right dose in your foods or in the right dose and supplements, they can actually activate these pathways in the right way.

William Li:

This whole idea of food dosing and hormesis, I love that you bring that up because that is such an important construct that anybody in the medical community will know that the teaching of the drug companies is that a little bit’s not enough, and then you want to increase the dose until you get the maximal tolerated dose. That’s how drugs are developed. That’s how chemotherapy is developed. How high can you make the dose until you basically make the person croak? That’s really how drugs are developed and yet that’s not how biology is. When we have that symbiotic relationship with plants, which I totally agree with, and by the way, humans aren’t the only ones that do this, bears go out and forge for berries, for specific kinds of things. Insects go out and look for specific types of plants and pollen to be able to service their own systems as well. We’re all tearing a page of the playbook of every other living species on the planet.

Dr. Mark Hyman:

For sure.

William Li:

At the end of the day, those goes back to the plant-based foods. But here’s I think what’s really cool. We can actually think about this hormesis concept is so important. A little might not be enough, a little bit more might be better, even more might actually get you where you want to be, and then when you go way overboard, you actually get less of an effect. By the way, this is a lesson I think that people need to hear about dietary supplements, because you get your quercetin, you get chlorogenic acid, you get your lycopene, you get your whatever it is, and the thinking is for a lot of people who are not savvy to the idea of hormesis is that more isn’t always more. At some point, more is less, may not be toxic, but you might actually move away from the benefit that you would get from it.

Dr. Mark Hyman:

It’s really fascinating. It’s like, what’s the Goldilocks dose of all these things. We can actually start to use these things to regulate our biology and our metabolism in ways that you’re discovering for all your research, which is so important, because I think as a doctor, we don’t think about these things. I don’t think we think about the power of these compounds and, in fact, in your book and in our conversations, you talked about this incredible sort of way in which often these compounds work better than drugs. I remember this one slide, we’re at a Milken conference together and you were presenting to the food companies and everybody, it was great. You threw up this slide, it said, here’s a drug for high blood pressure and here’s this food and here’s the effect.

I’m like, wait a minute. I’ve never seen that before. It was so profound and we see that. We see when I use food as medicine with my patients in my practice and understand like any pharmacology, you have to know the right drug and the right dose for the right person, for the right problem. It’s literally that specific. When you do that, you see results that are far more profound than what you see with regular medication. You reverse diabetes and heart failure and kidney failure and liver problems and autoimmune diseases and digestive disorders. I saw it in myself. I mean, I had an incurable autoimmune disease, which I developed after getting C. diff, which is a terrible infection. I developed ulcerative colitis and I was having 20 bloody bowel movements a day. I lost 20 pound. I was in bed. I couldn’t work. I was like, this is terrible.

Actually, in part due to our conversations and what I learned from you about the power of Akkermansia and other things, I tested and I had like zero Akkermansia, like zero. And so, I developed this Akkermansia shake, which I did based on a lot of things I learned from you and research, and I started taking it and actually reset my whole system. I did a bunch of other things, but we now can use these compounds as part of a therapeutic framework and understand that food really is medicine. It’s not just like medicine.

William Li:

Well, I’m working on my next book right now, which will come out next year. What I’m doing is taking everything that I started my first book and diving a lot deeper into how many of the same foods and some new ones actually can actually alter our metabolisms as well, but the big eyeopener for me as a scientist, and by the way, for people who are not scientists, the fun part of being a scientist is we get to discover new things that open our eyes, drop our jaws, and make us actually kind of jump for joy because we’ve discovered something new. And so, what I’m actually realizing is that this idea of reversing disease, which is what you’ve just described for yourself, which sounds miraculous when one says it, actually isn’t that miraculous at all.

It’s really helping our body reset. It’s like having that spinning wheel of death and you do a hard reboot, you got to do different things to actually get your operating system to go back to what it wants to do. I mean, at some point, you can actually go over the edge and you can’t rescue the system. You got to get a new laptop, but actually, more times than not, we can actually do daily things. This is the food is medicine, the medicine we take three times a day that put the right stuff into our bodies, the right type of calories, the right type of micronutrients and macronutrients. By the way, not to understate the fact that food isn’t a cure-all, this whole idea of lowering stress. By the way, right now, post kind of this whole pandemic craze and all the political and military upset that’s going around the world now, the monkeypox, we live in a dooms scrolling society.

Dr. Mark Hyman:

I tried not go in there.

William Li:

What happens though and I think this is so important to hear is that one thing that I found it helpful for me, because I was getting as a researcher in different diseases is I started to find myself looking deeper and deeper into what is going on just like a researcher, and I inadvertently found myself doom scrolling. And so, that’s something that I think that we can knowledgeably not do. You can undo that by taking some time away. Here’s what I did. I went to the Mediterranean to do some research on food. It was a complete reset when I was just with sea, sky, rock, and elemental foods. I’m sure the same way with you.

Dr. Mark Hyman:

Totally. It was a great excuse. I’m writing a book and like had to go to a Korea, one of the blue zones and I ate all the wild greens they had, the wild mushrooms. I ate their wild sage tea, which has the high level [inaudible 00:50:47].

William Li:

We were FaceTiming back and forth. I was so amazed, but you know, when you share that experience with others because you actually know what it’s like, what I’m trying to say is that stress is something that we have to live with now. It’s possible to unplug and find simple ways to go back to a simpler sort of regimen in our life and something that’s just unplugging from information.

Dr. Mark Hyman:

It’s true. I mean, I literally don’t really, I mean, I think if some big news thing happens, I’ll hear about it. Then, I’ll look at it if I need to, but I just sort of unloaded my nervous system and it’s like junk food for the brain and for your soul. I try to stay away from it.

William Li:

Ultra processed news.

Dr. Mark Hyman:

Ultra processed news, not even news and all the good stories don’t get told. There’s a lot of hope out there. I just want to spend last two minutes kind of getting a little bit granular on how you would tell your patients to take this information about metabolism that you’ve learned, how do they begin to incorporate it in their lives on a daily basis? How can they kind of accelerate their healing, speed of metabolism, and reach their health potential?

William Li:

Listen, I mean, because this is my new deep area of research, I’m not going to go into the complex. I’m going to go for the simple things. Turns out for your metabolism, that what you eat and how you live can actually help to restore the metabolism that you are destined to have born with, which is the same as everyone else. All right. You’re not doomed by your genetics. You’re capable of actually restoring your own healthy metabolism. If you listen to the Dr. Mark Hymans of the world, you can actually elevate them as well, which to me is an inspirational message that you can actually not just claw your way back to where you started, but you can actually even get better.

To me, how do you do that? You do that by actually a lot of the common sensing that over and over we’ve been saying, eat mostly plant-based foods, whole foods, fruits and vegetables, nuts, legumes, healthy oils, avoid excessive, unhealthy fats. All right. Omega-3s, which come from seafood and seaweed are also great compliments. Look, I’m somebody who really enjoys food. I don’t love to eat, but I enjoy food and I love the traditions of food. It’s okay, you don’t have to be a vegan to enjoy your life and you should live your life, but what you need to do is that you’re tending your own body’s garden. You need to make sure you’re taking care of it most of the time. Taking care of it of not only eating well, cooking it the right way. Omega-3 healthy, a piece of salmon. If you deep fry it and turn it to fish and chips, it’s like what we do to our food even at home actually can make the difference between turning something that’s good and making it better versus taking something that’s good and taking it less good for you.

Dr. Mark Hyman:

For sure.

William Li:

That’s something, it’s in your hands. Then, of course, the simple things like staying physically active, getting good quality sleep, managing stress, those are all the composite things that those systems, we started at the very beginning of this podcast talking about all these molecular systems and the microbiome. Look, you don’t need to memorize all the things that folks like you and I are uncovering, but what you do need to understand is that how you schedule your life, how you run your life has a profound effect, this domino effect on all the things inside. Do good things for yourself. Do a good deed for yourself every single day, three times a day, and while you’re sleeping at night. That’s the secret to actually helping your metabolism.

Dr. Mark Hyman:

I love it. Well, thank you. This is great. We’re going to keep talking more. I’m definitely going to put these articles on the show notes, the ones that I mentioned about competing paradigms of obesity and why we get it and the unexplained epidemic and how the whole thinking about this is wrong, and what you’re talking about in terms of the quality of food, about the phytochemicals in food, about all these other influences on our metabolism plays such a huge role. Thank you for your work. William, you’re an incredible guy and a brilliant scientist. Thank you for lending your genius to this topic, because you’re kind of the real-deal scientist. I’m just kind of a big talking head seeing a lot of patients, but I’ve done a little bit of research, but you really are understanding this and bringing this to people in such a beautiful way. I am so grateful for that.

For those of you listening, if you love this podcast, share it with your friends and family on social media. We’d love to hear from you how have you used food to help speed up your metabolism and help you improve your health. Subscribe wherever you get your podcast and we’ll see you next week on The Doctor’s Farmacy.

Closing:

Hi, everyone. I hope you enjoyed this week’s episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you’re looking for help in your journey, seek out a qualified medical practitioner. If you’re looking for a functional medicine practitioner, you can visit ifm.org and search their find a practitioner database. It’s important that you have someone in your corner who’s trained, who’s a licensed healthcare practitioner, and can help you make changes especially when it comes to your health.

If you are looking for personalized medical support, we highly recommend contacting Dr. Hyman’s UltraWellness Center in Lenox, Massachusetts today.

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